Now showing items 21-40 of 1518

    • Exploiting Natural Language Processing to Unveil Topics and Trends of Traumatic Brain Injury Research

      Karabacak, Mert; Jain, Ankita; Jagtiani, Pemla; Hickman, Zachary L.; Dams-O'Connor, Kristen; Margetis, Konstantinos (Mary Ann Liebert Inc, 2024-03-01)
      Traumatic brain injury (TBI) has evolved from a topic of relative obscurity to one of widespread scientific and lay interest. The scope and focus of TBI research have shifted, and research trends have changed in response to public and scientific interest. This study has two primary goals: first, to identify the predominant themes in TBI research; and second, to delineate "hot" and "cold" areas of interest by evaluating the current popularity or decline of these topics. Hot topics may be dwarfed in absolute numbers by other, larger TBI research areas but are rapidly gaining interest. Likewise, cold topics may present opportunities for researchers to revisit unanswered questions. We utilized BERTopic, an advanced natural language processing (NLP)-based technique, to analyze TBI research articles published since 1990. This approach facilitated the identification of key topics by extracting sets of distinctive keywords representative of each article's core themes. Using these topics' probabilities, we trained linear regression models to detect trends over time, recognizing topics that were gaining (hot) or losing (cold) relevance. Additionally, we conducted a specific analysis focusing on the trends observed in TBI research in the current decade (the 2020s). Our topic modeling analysis categorized 42,422 articles into 27 distinct topics. The 10 most frequently occurring topics were: "Rehabilitation," "Molecular Mechanisms of TBI," "Concussion," "Repetitive Head Impacts," "Surgical Interventions," "Biomarkers," "Intracranial Pressure," "Posttraumatic Neurodegeneration," "Chronic Traumatic Encephalopathy," and "Blast Induced TBI," while our trend analysis indicated that the hottest topics of the current decade were "Genomics," "Sex Hormones," and "Diffusion Tensor Imaging," while the cooling topics were "Posttraumatic Sleep," "Sensory Functions," and "Hyperosmolar Therapies." This study highlights the dynamic nature of TBI research and underscores the shifting emphasis within the field. The findings from our analysis can aid in the identification of emerging topics of interest and areas where there is little new research reported. By utilizing NLP to effectively synthesize and analyze an extensive collection of TBI-related scholarly literature, we demonstrate the potential of machine learning techniques in understanding and guiding future research prospects. This approach sets the stage for similar analyses in other medical disciplines, offering profound insights and opportunities for further exploration.
    • Exploring the roles of the connecting cilium in photoreceptor health

      Liu, Yu (2024-03-26)
      Defects in proteins functioning at the photoreceptor connecting cilium/transition zone (CC/TZ) have been linked to retinal degenerative disorders such as retinitis pigmentosa (RP) and cone-rod dystrophy (CRD). Mutations in eyes shut homolog (EYS, RP25), a secreted ciliary protein with laminin globular (LG) domains, have been linked to RP and CRD. Previously, some LG domains have been shown to interact with O-mannosyl glycans of α-dystroglycan (α-DG). Additionally, mutations in pomgnt1, an enzyme that plays a critical role in the synthesis of these glycans, have also been linked to RP (RP76). At the CC/TZ, the tectonic protein complex functions to maintain the unique biochemical environments of the inner segments (IS) and outer segments (OS) of photoreceptors. Mutations in tectonic complex proteins have been linked to ciliopathies that often include ocular abnormalities. The pathogenic mechanism underlying these mutations are poorly understood; thus, we hypothesized that EYS is an extracellular ciliary protein that interacts with α-DG and the tectonic complex. This project investigated the role of EYS, TMEM216, a member of the tectonic complex, and O-mannosyl glycans of α-DG in photoreceptor health. We determined that the C-terminal LG domains of EYS interacted with the O-mannosyl glycan epitope of α-DG. In pomgnt1 zebrafish mutants, EYS-glycan binding was reduced, and the secretion of EYS to the CC/TZ was significantly disrupted. Furthermore, in the pomgnt1 mutant retina, a substantial accumulation of EYS protein was observed in the soma of photoreceptors. Interestingly, deletion of pomgnt1 resulted in a pattern of photoreceptor degeneration similar to that previously observed in eys zebrafish mutants. By contrast, deletion of TMEM216 did not disrupt localization of EYS or of other tectonic complex proteins, yet photoreceptor degeneration was still observed in these animals. Our study has identified a previously unknown interaction between the LG domain-containing EYS and O-mannosyl glycans. These findings provide novel insight into the functional role of EYS around the CC/TZ and suggest the importance of O-mannosyl glycosylation in the regulation of protein secretion. Furthermore, our results suggest a mechanistic link between the disruption of glycosylation and photoreceptor degeneration, providing a new perspective on the underlying mechanisms behind RP25 and RP76.
    • Modeling exposure to folate receptor antibodies during neural development to understand its clinical significance.

      Bobrowski-Khoury, Natasha
      Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental disorder with defined core symptoms of impaired social communication, stereotyped or repetitive behaviors, and cognitive deficits. These core symptoms present early in childhood, which distinguishes this disorder from other neurological disorders that share similar characteristics. To our knowledge, there is currently no pharmacologic treatment for the core symptoms of ASD. A possible therapeutic strategy is supplementing folate, more specifically the reduced form, folinic acid, during pregnancy. Folate is the umbrella term for biological forms of vitamin B9. The well recognized role of folates as precursors of DNA synthesis, single carbon exchange reactions and in methylation reactions is a priori evidence of its requirement for cellular replication, metabolism, and epigenetic control of gene expression. This is especially important during the early stages of neural development. While the role of folate in cellular metabolism has been clearly defined, there has been no study, to our knowledge, that demonstrates the characteristics of folate uptake and distribution during gestation and early development. This is critical to understand because of the emerging findings that folate receptor alpha autoantibodies (FRAuAb) are linked to disruptions of neural development leading to ASD. Our lab has shown that a rat model of exposure to IgG antibodies specific to rat folate receptor alpha during gestation develops a behavioral phenotype comparable to the human ASD. This phenotype appears to be preventable with folinic acid and dexamethasone treatment. Preliminary observations in this model also suggest that the phenotype seen in rats directly exposed to FRAb is preserved in subsequent generations. Overall, this thesis provides new data on the uptake and distribution of folate and folate receptor antibodies in utero (Study 1, Part 1) and in juvenile stages of development (Study 1, Part 2) and observes an appearance of deficits to a subsequent generation of animals previously exposed to FRAb directly (Study 2)
    • Assessment of knowledge, practice and perception of menstruation among adult women in the reproductive age group, in Mangalore, India

      Kotian, Shashidhar M.; Chaudhary, Vyom K.; Mutya, Venkata S.; Sekhon, Anurag S.; Sriraman, Sheetal; Prasad, Prashasti (Medip Academy, 2017-09-23)
      Background: Women often lack knowledge regarding reproductive health including menstruation which can be due to socio-cultural barriers in which they grow up. The present study is aimed at assessing the level of knowledge regarding menstruation and hygienic practices and perceptions during menstruation. Methods: It was a cross sectional study, conducted among 110 adult women to assess their knowledge regarding menstruation, practices followed during menstruation and their perceptionof menstruation. The collected data was analyzed using SPSS version 17. 0. Chi square test was applied. P<0.05 was considered to be significant. Results: Only 52% of the study population has satisfactory knowledge regarding menstruation. Women between 15 to 20 years of age and those from the middle and higher socio-economic groups seem to possess maximum knowledge regarding menstruation. Women of the higher socio-economic group practice better sanitary measures during menstruation with 100% of them using pads, as compared to women of lower socio economic group who showed a trend of using cloth (87.5%). Women of the upper socio-economic class (42.78%) had better perception towards menstruation (p<0.05). Conclusions: It is very important that lower socio-economic group should be educated about the importance of maintaining hygiene during menstruation by proper health education and equip them with skills regarding safe and hygienic practices to prevent the risk for reproductive tract infections.
    • Knowledge, Utilization and Benefits of a Child Health Care Scheme

      Sriraman, Sheetal; Baliga, Shantharam; Unnikrishnan, Bhaskaran; Kamath, Nutan (JCDR Research and Publications, 2017-11-01)
      Introduction: Child health plays an essential role in shaping the future of a community. For this reason, governments worldwide have made child health care a priority. Studying the trends of utilization and benefits of child health care schemes is therefore, imperative to assess its impact on the community. Aim: This study was undertaken to assess the knowledge, utilization and benefits of a child health care scheme Bal Sanjeevani Program (BSP) in a Government District Hospital. Materials and Methods: Hundred children belonging to Below Poverty Line (BPL) families, between 0 to 6 years of age admitted for tertiary care were divided equally into cases and controls. The children who availed the BSP were enlisted as the case, whereas those who did not avail the benefits of the BSP were enrolled as the control. The study was conducted in March and April 2016. A semi-structured questionnaire was used for data collection, after approval of the Institutional Ethics Committee. Data analysis was done using SPSS 16.0. Descriptive statistics as well as the Chi-square test were used for analysis. Results: Of the respondents, 61(61%) had heard of the BSP, of which 11(22%) chose not to register for the scheme. Of those not availing the scheme, 39(78%) stated lack of awareness as the main reason for non-utilization. The mean expenditure of those not utilizing the scheme was 12.87 times more than that of the mean expenditure of those utilizing the scheme. Conclusion: This program significantly alleviates the financial burden on families with children admitted in tertiary care centers. Increasing the awareness regarding the BSP and identifying eligible children at the Primary Health Care (PHC) level would enhance optimum utilization of this scheme.
    • Patient handling in India—Evidence from a pilot study

      Koshy, Nidhin; Sriraman, Sheetal; Kamat, YogeeshD (Medknow, 2020-03-26)
      Background: Manual handling forms an important part of a health care worker's daily routine. Faulty techniques may result in musculoskeletal injuries in health workers and further injury to patients. Objectives: In our study, we assessed the techniques of patient moving and handling by health care workers in our hospital. Our aim was to educate them on standard moving and handling techniques and assess the impact of the same. Methods: We carried out a time-bound prospective clinical audit wherein we observed workers in the emergency department for a period of 2 weeks to evaluate their moving and handling techniques. This was followed by a training session where the workers were trained in "best-practices," and a 2-week period of reevaluation to assess compliance with standard practices. Results: During bed-to-bed transfers, we found improvements in the following seven parameters after the training session: (a) the use of good posture, (b) the use of wheel stoppers, (c) adjustment of bed height, (d) positioning the receiving bed parallel to patient's bed, (e) general risk assessment before transferring a patient, (f) involvement of at least three carers, and (g) the use of a standard command like "GO" before the transfer. Conclusion: Apart from serving the purpose of an audit, our study has revealed that the training of health care providers in safe moving and handling of patients is a neglected subject in India.
    • Internalized stigma related to COVID-19 and its psychosocial and mental health correlates: a multicentric health facility based observational study from Nepal

      Shah, Bigya; Mahapatra, Ananya; Singh, Uday Narayan; Mishra, Vilok; Daha, Sunil Kumar; Pande, Rajan; Neupane, Madan Ratna; Banjade, Anita; Khatik, Chandra Bhal; K. C., Tej Bahadur; et al. (Frontiers Media SA, 2024-02-14)
      Introduction: The COVID-19 pandemic has led to physical and psychological complications and social consequences in the form of illness-related stigma. This study aimed (1) to assess the sociodemographic and clinical variable, as well as COVID-19 related knowledge and perception of persons admitted for COVID-19/Suspected COVID-19 in Nepal, (2) to determine their levels of COVID-19- related internalized stigma, depression, and anxiety symptoms, and (3) to evaluate the correlates of COVID-19- related internalized stigma. Materials and methods: It was a cross-sectional exploratory study with a convenience sample of 395 participants (306 confirmed cases, 89 suspected cases) conducted between July-October 2020 in four health facilities in Madhesh and Lumbini provinces of Nepal. We used a semi-structured questionnaire to assess sociodemographic details, clinical information, COVID-19-related knowledge, perception, COVID-19-related internalized stigma, and the Hamilton Anxiety Depression Scale (HADS) in Nepali language. Descriptive statistics, correlation analyses, and linear regression analyses were performed. The level of statistical significance was considered at p < 0.05. Results: Around 23.3% of the patients had anxiety symptoms, 32.9% had depressive symptoms, and 20.3% had high COVID-19-related internalized stigma (mean ISMI score: 2.51-4.00). Linear regression analyses showed a significant positive association of COVID-19-related internalized stigma total score, with the following eight factors, i.e., no income in the past one month (p = 0.013), below average socioeconomic status (p = 0.004), anxiety symptoms (p = <0.001), depressive symptoms (p = <0.001), recent testing positive for COVID-19 (p = <0.001), involuntary admission (p = <0.001), prior experience of being in isolation and quarantine (p = 0.045), and those who blame others for COVID-19 (p = 0.025). Conclusion: COVID-19 survivors and suspects are vulnerable to symptoms of depression, anxiety, and COVID-19-related internalized stigma. For the first time from Nepal, our data suggests that COVID-19-related internalized stigma is associated with anxiety and depression symptoms, perceived below-average socioeconomic status, involuntary admission, prior experience of being in isolation and quarantine, recent COVID-19 positive report, self-blame, below-average socioeconomic status and no income in the past one month. Mitigating and preventing internalized stigma associated with a public health crisis such as COVID-19 is imperative by diagnosing and treating such mental health issues early and designing interventions and policies especially targeting vulnerable populations focusing on their economic background and socio-cultural beliefs.
    • Lung lymphatic endothelial cells undergo inflammatory and prothrombotic changes in a model of chronic obstructive pulmonary disease

      Trivedi, Anjali; Lu, Tyler M.; Summers, Barbara; Kim, Kihwan; Rhee, Alexander J.; Houghton, Sean; Byers, Derek E.; Lis, Raphaël; Reed, Hasina Outtz (Frontiers Media SA, 2024-02-19)
      The lymphatic vasculature regulates lung homeostasis through drainage of fluid and trafficking of immune cells and plays a key role in the response to lung injury in several disease states. We have previously shown that lymphatic dysfunction occurs early in the pathogenesis of chronic obstructive pulmonary disease (COPD) caused by cigarette smoke (CS) and that this is associated with increased thrombin and fibrin clots in lung lymph. However, the direct effects of CS and thrombin on lymphatic endothelial cells (LECs) in COPD are not entirely clear. Studies of the blood vasculature have shown that COPD is associated with increased thrombin after CS exposure that causes endothelial dysfunction characterized by changes in the expression of coagulation factors and leukocyte adhesion proteins. Here, we determined whether similar changes occur in LECs. We used an in vitro cell culture system and treated human lung microvascular lymphatic endothelial cells with cigarette smoke extract (CSE) and/or thrombin. We found that CSE treatment led to decreased fibrinolytic activity in LECs, which was associated with increased expression of plasminogen activator inhibitor 1 (PAI-1). LECs treated with both CSE and thrombin together had a decreased expression of tissue factor pathway inhibitor (TFPI) and increased expression of adhesion molecules. RNA sequencing of lung LECs isolated from mice exposed to CS also showed upregulation of prothrombotic and inflammatory pathways at both acute and chronic exposure time points. Analysis of publicly available single-cell RNA sequencing of LECs as well as immunohistochemical staining of lung tissue from COPD patients supported these data and showed increased expression of inflammatory markers in LECs from COPD patients compared to those from controls. These studies suggest that in parallel with blood vessels, the lymphatic endothelium undergoes inflammatory changes associated with CS exposure and increased thrombin in COPD. Further research is needed to unravel the mechanisms by which these changes affect lymphatic function and drive tissue injury in COPD.
    • Factors Influencing Social and Community Participation of People with Spinal Cord Injury in Karnataka, India

      Babu, Heavenna; Sriraman, Sheetal; Karthikbabu, Suruliraj; Sophia, P.; Kumar, Senthil N. S. (Medknow, 2024-01-12)
      Background: Social and community participation are major indicators to assess the adequacy of treatment and rehabilitation in patients with spinal cord injury (SCI). This study examined the relationship between functional independence, level of disability, and social and community participation among people with SCI in India. Materials and method: In this cross sectional study, 110 persons with SCI, aged 18 years and above participated in a community setting, in Karnataka, India. Spinal Cord Independence Measure Version III-self-reporting (SCIM III-SR), Craig Handicap Assessment and Reporting Technique (CHART), and WHO Disability Assessment Schedule 2.0 (WHODAS) were the clinical outcome measures. Spearman's correlation and stepwise multiple linear regression were done to determine association and identify the factors determining the community participation of people with SCI. Results: CHART physical independence had a positive correlation with SCIM self-care (R = 0.446) and SCIM mobility (r = 0.434). CHART cognitive independence (R = -0.38) and CHART mobility (R = -0.396) had a weak correlation with WHODAS. SCIM self-care and SCIM mobility (R2 = 0.34) were determinants of CHART cognitive independence. SCIM respiratory and sphincter management and SCIM self-care (R2 = 0.327) were determinants of CHART mobility. Conclusion: Self-care and mobility of people with SCI determine their ability to successfully reintegrate into the community, warranting a comprehensive community rehabilitation program.
    • The New Urology Match: How Recent Innovations Including Virtual Interviews and Preference Signaling Have Changed Match Outcomes

      Heard, John; Rawal, Rushil Y; Amazan, Bradley; Jeune, Karl-Ray; Freedman, Andrew (Springer Science and Business Media LLC, 2024-01-29)
      Objectives: To determine how recent changes in the urology match occurring from 2021 to 2023, including virtual interviews (VIs) and preference signals (PS), affected match outcomes. Methods: The American Urological Association (AUA) match data from 2021 to 2023 was compared to the 15 years prior. This was obtained from the AUA website and a previous study of public AUA match data. Self-reported applicant characteristics and outcomes from the Urology Residency Applicant Spreadsheet 2021-2023 were compared to the four years prior. Results: Between 2021 and 2023, residency programs offered 43 interviews each, compared to an average of 35 in the 15 years prior. Programs have been receiving more applications each year, from a low of 225 in 2019 to a peak of 347 in 2022. This resulted in an interview offer rate of 13% between 2021 and 2023, compared to 16% in the five years prior. Applicants applied to a mean of 88 programs in 2023, increasing each year since 40 in 2006. Applicants attended 12 interviews on average between 2021 and 2023, compared to 13 in the two years prior. Self-reported applicant data similarly demonstrated that, compared to the four years prior, applicants between 2021 and 2023 applied to more programs (81 vs. 70), had a lower interview offer rate (22% vs. 32%), and a higher interview acceptance rate (90% vs. 75%). Conclusions: During the years with VIs, programs offered more interviews and applicants attended fewer on average, indicating a larger applicant pool was interviewed. Despite the introduction of PS, applicants applied to more programs in 2022 and 2023 than ever before.
    • Gender and disease-inclusive nomenclature consolidation of theragnostic target, prostate-specific membrane antigen (PSMA) to folate hydrolase-1 (FOLH1)

      Ramirez-Fort, Marigdalia K.; Gilman, Casey K.; Alexander, Jacob S.; Meier-Schiesser, Barbara; Gower, Arjan; Olyaie, Mojtaba; Vaidya, Neel; Vahidi, Kiarash; Li, Yuxin; Lange, Christopher S.; et al. (Frontiers Media SA, 2024-02-09)
    • IPSC-derived neurons as a model for studying the role of RELN in autism

      Mohktari, Ryan (2024-03-11)
      RELN is strongly associated with Autism Spectrum Disorder (ASD). Homozygous loss of the encoded protein REELIN is associated with severe neurodevelopmental phenotypes characterized by lissencephaly and cerebellar hypoplasia, yet the ASD linked variants are typically heterozygous and appear to require additional genetic risk to cause ASD. To functionally characterize a RELN variant in a patient with ASD, we used induced pluripotent stem cells (iPSCs) from a family of non-autistic parents and their son who had ASD (the proband). The proband has a maternally-inherited missense variant (R2457C) in the RXR motif of the REELIN protein. We differentiated the iPSCs into two types of neurons, inhibitory neurons which model the inhibitory forebrain neurons that secrete REELIN, and excitatory neurons which model the cortical pyramidal neurons that respond to REELIN. Immunoblotting revealed that the proband inhibitory neurons had a lower ratio of extracellular/intracellular REELIN compared to that of the parental neurons, suggesting a decreased REELIN secretion. Sholl analysis on the proband excitatory neurons showed reduced dendritic complexity and reduced total length compared to the parental neurons. REELIN treatment increased the dendritic length and complexity in proband neurons up to the level of parental neurons. CRISPR/Cas9-mediated RELN KO did not change the dendritic phenotype in the excitatory neurons, ruling out a cell autonomous role for REELIN in these neurons. The proband excitatory neurons also had lower mRNA expression of WNT target genes in response to WNT3a, suggesting an underactive WNT signaling, as well as higher total GSK3β protein and lower phosphorylation at the inhibitory S9 site, indicating an overactive GSK3β signaling. Inhibition of GSK3β improved the proband neurons dendritic complexity in the proximal parts of the dendritic arbor. However, inhibition of mTOR signaling, which has shown to regulate REELIN signaling, did not change the dendritic morphology. In conclusion, the pathophysiology of ASD in the proband likely consists of a reduced REELIN secretion from the inhibitory neurons and an additional vulnerability in the REELIN-responding excitatory neurons, the latter likely being an overactive GSK3β and an underactive WNT signaling, all of which result in reduced dendritic complexity.
    • Interaction effect of race-ethnicity and dementia on COVID-19 diagnosis among a national US older adult sample

      Wong, Roger; Grullon, Jason Rafael (Cambridge University Press, 2024-03-14)
      Older racial and ethnic minorities and older adults with dementia have an elevated COVID-19 risk, warranting research into the intersection between these two high-risk groups. We examined whether race-ethnicity moderates the association between dementia and COVID-19 diagnosis. Data were retrieved for 3189 respondents from a nationally representative prospective cohort sample of US older adults aged 65+ years. We analysed the effects of the interaction between race-ethnicity and dementia on COVID-19 diagnosis, after adjusting for sociodemographic factors, health and COVID-19 mitigation behaviours. The odds of COVID-19 diagnosis were significantly lower for Black older adults with dementia (adjusted odds ratio [aOR] = 0.07, 95% CI = 0.01-0.78, = 0.03). In addition, dementia increased the odds of COVID-19 diagnosis among Hispanic older adults (aOR = 1.59, 95% CI = 0.12-21.29, = 0.72), although this increase was not statistically significant. The interaction between race-ethnicity and dementia should be considered when assessing COVID-19 risk among older adults. Future research is needed to examine pathways through which dementia may interact with race and ethnicity to influence COVID-19 risk.
    • Monomeric DENV-reactive IgA contributes protective and non-pathologic functions during DENV infection

      Wegman, Adam (2024-01)
      Dengue, caused by the 4 serotypes of dengue viruses (DENVs), is a tropical and subtropical vector-borne febrile illness which causes a significant global disease burden. A particular immunological feature contributing to severe disease is antibody-dependent enhancement (ADE), in which IgG isotype antibodies raised during a primary DENV infection opsonize and enhance the infectivity of DENVs during a secondary heterotypic infection. We and colleagues have described a monomeric serum IgA response during dengue infection. Here, we report on the functional characteristics of monomeric IgA in DENV infection. We show that isotype conversion of IgG to IgA preserves neutralization capacity while abrogating enhancing capacity. We show that DENV-specific IgA competitively antagonizes both IgG-mediated infection and downstream secretion of pro-inflammatory cytokines. This effect is largely attributable to the lower avidity of IgA-DENV immune complexes for permissive cells compared to IgG-DENV complexes. These findings have implications for serodiagnosis, therapeutics, and assessing risk of severe disease.
    • Effects of Probiotics, Prebiotics, and Synbiotics on Messenger RNA Expression of Caveolin-1, NOS, and Genes Regulating Oxidative Stress in the Terminal Ileum of Formula-Fed Neonatal Rats

      D'Souza, Antoni; Fordjour, Lawrence; Ahmad, Asma; Cai, Charles; Kumar, Dharmendra; Valencia, Gloria; Aranda, Jacob V; Beharry, Kay D (Springer Science and Business Media LLC, 2010-05)
      Necrotizing enterocolitis (NEC) afflicts extremely low birth weight neonates, and probiotics reduces its incidence and severity. NO is involved in the pathogenesis of NEC, and caveolin-1 regulates NO signaling. We tested the hypothesis that intestinal caveolin-1 and NOS are deficient in formula-fed neonatal rats and that supplementation with "Florastar Kids" and/or galacto-oligosaccharides and fructo-oligosaccharides preserves caveolin-1 and NOS. At birth (P0), neonatal rat pups were maternally fed or hand-gavaged with or without supplemented formula. Samples from the terminal ileum were analyzed for total NO metabolites, growth factors, and gene expression of caveolin-1, NOS isoforms, and antioxidants. Our data showed that formula feeding with and without supplementation resulted in significant growth restriction. Despite suboptimal nutrition, growth factors involved in intestinal repair and regeneration were increased in the neonatal rat ileum. Caveolin-1, endothelial NOS, and neuronal NOS were simultaneously down-regulated with formula feeding while inducible NOS was up-regulated. Superoxide dismutase and glutathione peroxidase were up-regulated with supplementation. These data provide a probable mechanism for the benefits of supplemented formula for decreasing the severity of NEC by preserving the antioxidant systems.
    • Cytokines and Toll-like receptor signaling pathways in the terminal ileum of hypoxic/hyperoxic neonatal rats: benefits of probiotics supplementation.

      D'Souza, Antoni; Cai, Charles L; Kumar, Dharmendra; Cai, Fayme; Fordjour, Lawrence; Ahmad, Asma; Valencia, Gloria; Aranda, Jacob V; Beharry, Kay D (2012-04-10)
      Oxidative stress and inflammation are associated with the development of inflammatory bowel diseases such as necrotizing enterocolitis. We tested the hypothesis that probiotics, prebiotics or synbiotics (a combination of pre- and probiotics) is effective for prevention of inflammatory responses to formula-feeding in the terminal ileum of neonatal rats.
    • Benefits of pre-, pro- and Syn-biotics for lung angiogenesis in malnutritional rats exposed to intermittent hypoxia.

      Ahmad, Asma; Cai, Charles L; Kumar, Dharmendra; Cai, Fayme; D'Souza, Antoni; Fordjour, Lawrence; Ahmad, Taimur; Valencia, Gloria B; Aranda, Jacob V; Beharry, Kay D (2014-10-11)
      Extremely low birth weight and reduced caloric intake have significant adverse effects on lung development and are risk factors for bronchopulmonary dysplasia. Vascular endothelial growth factor (VEGF) is highly involved in lung microvascular development, and may be affected by nutritional status. To test the hypothesis that suboptimal nutrition decreases VEGF signaling in formula-fed neonatal rats, and to determine whether supplementation with probiotics, prebiotics, or synbiotics ameliorate the effects, rat pups at birth (P0) were placed in room air (RA) or intermittent hypoxia (12%) during hyperoxia (50% O2) from birth to P3. The pups were either maternally-fed; or formula-fed with or without supplementation. Formula-fed pups were separated from their mothers at birth and hand-gavaged every 3 hours. Lung VEGF signaling was determined on P3. In RA, all formula-fed groups were significantly growth suppressed with decreased lung weights. Hyperoxia had a less remarkable effect on body weight; and mean lung weight was lower only in the unsupplemented formula-fed group. Lung VEGF was decreased in all formula-fed RA and hyperoxia groups, except the probiotics group. In RA, sVEGFR-1 levels were elevated in all formula-fed groups except the synbiotics group. However in hyperoxia, sVEGFR-1 levels were higher in the unsupplemented formula group. All genes involved in angiogenesis were downregulated in the formula-fed groups compared to maternally-fed. Formula feeding results in significant malnutrition associated with decreased lung size and lung VEGF levels in neonatal rat pups. Probiotic supplementation prevented the adverse effects of combined hyperoxia and suboptimal nutrition on lung VEGF suggesting preservation of angiogenesis.
    • Growth factors in the fetus and pre-adolescent offspring of hyperglycemic rats

      Fordjour, Lawrence; Cai, Charles; Bronshtein, Vadim; Bronshtein, Mayan; Aranda, Jacob V; Beharry, Kay D (SAGE Publications, 2021-04-29)
      Background: Maternal hyperglycemia influences childhood metabolic syndrome, including obesity and hyperglycemia. We tested the hypothesis that the maternal hyperglycemia influences growth factors in the fetal and pre-adolescent offspring. Methods: Hyperglycemia was induced in pregnant rats on embryonic day (E)16 using streptozocin followed by implantation with insulin or placebo pellets at embryonic day 18 (E18). Fetuses at E20 and pre-adolescent pups at postnatal day 14 (P14) were studied: (1) normal untreated controls (CTL) at E20; (2) hyperglycemic placebo-treated (HPT) at E20; (3) hyperglycemic insulin-treated (HIT) at E20; (4) CTL at P14; and (5) HIT at P14. Fetal and pre-adolescent growth factors were determined. Results: Biomarkers of hypoxia were elevated in the HPT group at E20. This group did not survive to term. Maternal insulin improved fetal survival despite lower fetal body weight at E20, however, at normal birth (postnatal day 0 (P0)) and at P14, body weights and blood glucose were higher than CTL. These high levels correlated with aberrant growth factors. Maternal hyperglycemia influenced glucose-6-phosphate dehydrogenase, glucagon, insulin, interleukin-10, and leptin genes. Conclusions: The impact of maternal hyperglycemia on pre-adolescent glucose and body weight was not a consequence of maternal overnutrition. This suggests an independent link which may affect offspring metabolic health in later life.
    • A Case of Transient Neonatal Diabetes Mellitus Successfully Managed with Basal Rate only Insulin Pump

      Henry, Michael M; Arora, Sumeet; Umpaichitra, Vatcharapan; Kochummen, Elna; Ch’ng, Tong Wooi; Hagerty, Dawn; Ibrahim, Zachary; Perez-Colon, Sheila; Chin, Vivian L; Fordjour, Lawrence (2023-01)
      Introduction: Neonatal diabetes mellitus is a rare condition that presents in the first few weeks to months of life. The neonate presents with low birth weight, dehydration, and hyperglycemia with or without ketoacidosis. Management using insulin drip, subcutaneous insulin injection and continuous subcutaneous insulin infusion (CSII) each present their own challenges. There is risk of hypoglycemia even with tiny doses of insulin. Case: We present a case of transient neonatal diabetes mellitus (TNDM) due to paternal uniparental disomy at the 6q24 region, initially diagnosed late at DOL 29 due to the intermittent nature of hyperglycemia. The patient was born with low birth weight, macroglossia, umbilical hernia, and required repair of bilateral inguinal hernia. The other challenges involve management of insulin administration due to the limited amount of subcutaneous tissue in neonates as well as the minute doses of insulin required. Our patient was successfully managed with the most advanced insulin pump at the time with diluted insulin, using a basal rate-only regimen at total daily dose of 0.01-0.2u/kg/day, which is much lower than reported in the current literature. Additionally, this report shows that by titrating to pre-feed glucose, no episodes of hypoglycemia were noted. She had much less blood sugar variability and remained euglycemic. A 90-degree steel catheter was used successfully. Conclusion: TNDM due to paternal uniparental disomy at the 6q24 region can successfully be treated using basal rate-only CSII regimen, titrated to pre-feed glucoses, and 90-degree steel catheter.
    • The introduction of nursing led bubble-CPAP in a neonatal unit in Ghana: A 32-month observational report

      Fordjour, Lawrence; Washburn, Lisa; Darko, Elizabeth; Koffie, Vivian; Rabiu, Fauziya; Brako, Nana Okai; Sereboe, Nana; Seidel, Corey; King, Bryan; Bodkin, Darren; et al. (Elsevier BV, 2023-10)
      Neonatal deaths account for nearly 50 % of under-five deaths in Ghana with prematurity as the leading factor. Bubble continuous positive airway pressure (bCPAP) is important in treating respiratory distress (RD) associated with prematurity but its use in Africa is challenging. There is limited equipment to care for vulnerable newborns and insufficiently trained healthcare staff. This 32-month observational study describes the characteristics and outcomes of bCPAP treated newborns as a nursing led intervention at a regional referral hospital in Ghana. In May 2014, bCPAP was introduced to newborn intensive care unit (NICU) nursing staff. Three bCPAP machines and supplies were donated by Medical Technology Transfer and Services (MTTS). A training program provided learning opportunities for US-based and Ghanaian staff. Locally collected data included: NICU census, staffing, admitting diagnosis, birth weight, gestational age, Apgar scores, antenatal corticosteroid administration, days on bCPAP, and survival. From May 2014 to December 2016, 189 newborns received bCPAP. The mean ± SD (range) gestational age was 30.0 ± 4.2 (24–42) weeks, birth weight was 1.5 ± 0.7 (0.5–4.25) kg, and bCPAP duration was 3.2 ± 3.3 (0–14) days. In 155 (82.0 %), the admission diagnosis was prematurity with RD. Survival in this group was higher compared to other diagnostic categories and improved as birthweight increased (p < 0.05). Overall, 57.8 % of bCPAP treated newborns survived, but survival decreased during the last 12 months for newborns < 1.5 kg. This study supports the long-term sustainability of a nursing-led bCPAP program in Africa, but positive outcomes may be compromised by staffing, equipment, and resource limitations.