Delays in diagnosing pulmonary tuberculosis within a context of medium incidence, Medellín, Colombia, 2017: an operational research.

BACKGROUND: Delay in tuberculosis (TB) diagnosis is one of the first obstacles for controlling the disease. Delays generate greater deterioration of the health of the patients and increase the possibilities of transmission and infection at home and in the community. The aim of the study was to identify profiles and individual variables associated with patient delays and health care system delays in patients with pulmonary tuberculosis (PTB) in Medellín, Colombia, a city that notifies 1400 new cases per year. METHODS: A retrospective cohort study in adults with PTB was conducted from May to September of 2017. Sociodemographic, health care-seeking behaviour, and clinical variables were measured. The outcomes were patient delay and health care system delay. The data were obtained from records of the local TB program, and a questionnaire was applied by the health care team that performs routine field visits. Simple correspondence analysis was used to identify groups (profiles), and their characteristics. Cox's proportional hazards model was carried out to identify the variables associated with the delays. RESULTS: The study included 183 patients. The total delay median was 101 days (IQR: 64-163). Patient delay was of 35 days (IQR: 14-84), the profile with greater delay belonged to consumers of psychoactive substances. The health care system delay was of 27 days (IQR: 7-89), the attributes of the profile with greater delay were being a female, having more than two consultations before the diagnosis, and having prescribed antibiotics. Basic-medium educational level [HRa = 0.69; 95% CI (0.49-0.97)] and having a TB home contact [HRa = 0.68; 95% CI (0.48-0.96)] were associated with greater patient delay. Having negative acid-fast bacilli (AFB) smear [HRa = 0.64; 95% CI (0.45-0.92)] and more than two consultations before the diagnosis [HRa = 0.33; 95% CI (0.22-0.49)] was associated with greater health care system delay. CONCLUSIONS: Data from epidemiological surveillance allowed locating risk groups with delays in TB diagnosis which requires the prioritisation of the local TB control program to promote early detection and prevention of adverse outcomes.

Bumetanide Suppression of Angiogenesis in a Rat Model of Oxygen-Induced Retinopathy.

Aquaporins (AQPs) are involved in hypoxia-induced angiogenesis and retinal damage. Bumetanide is a diuretic agent, Na+/K+/Cl- cotransporter (NKCC1), and AQP 1-4 inhibitor. We tested the hypothesis that early postnatal treatment with bumetanide suppresses biomarkers of angiogenesis and decreases severe retinopathy oxygen-induced retinopathy (OIR). Neonatal rats were exposed at birth (P0) to either (1) room air (RA); (2) hyperoxia (50% O2); or (3) intermittent hypoxia (IH) consisting of 50% O2 with brief, clustered episodes of 12% O2 from P0 to postnatal day 14 (P14), during which they were treated intraperitoneally (IP) with bumetanide (0.1 mg/kg/day) or an equivalent volume of saline, on P0-P2. Pups were examined at P14 or allowed to recover in RA from P14-P21. Retinal angiogenesis, morphometry, pathology, AQPs, and angiogenesis biomarkers were determined at P14 and P21. Bumetanide reduced vascular abnormalities associated with severe OIR. This was associated with reductions in AQP-4 and VEGF. Bumetanide suppressed sVEGFR-1 in the serum and vitreous fluid, but levels were increased in the ocular tissues during recovery. Similar responses were noted for IGF-I. In this model, early systemic bumetanide administration reduces severe OIR, the benefits of which appear to be mediated via suppression of AQP-4 and VEGF. Further studies are needed to determine whether bumetanide at the right doses may be considered a potential pharmacologic agent to treat retinal neovascularization.

Comparing musicians and non-musicians in signal-in-noise perception.

Objectives: The objective is to compare musicians and non-musicians in signal-in-noise perception.Design: Participants underwent the following tests: (1) High-frequency (HF) audiometry, (2) QuickSIN (a test for speech perception in noise), and (3) Binaural Masking Level Difference (BMLD) test (a test that examines the hearing threshold of a low-frequency tone from noise masking when the phase of the signal or noise in one ear is reversed with respect to the phase of the signal or noise in the other ear, i.e. the difference in the threshold for detection of the tone in noise under the SπNo and SoNo conditions).Study sample: Thirty-four healthy young normal-hearing listeners including 17 musicians (M) and 17 non-musicians (NM).Results: There were no study group difference in HF audiometry and QuickSIN. The M group had a significantly better performance under the SoNo but not under the SπNo condition. As a result, the BMLD value (SoNo-SπNo) was significantly smaller in the M group than in the NM group.Conclusions: There is a musicians' advantage in binaural tone-in-noise detection in the BMLD task under the SoNo condition, suggesting that long-term music training positively shapes the auditory system.

Human retinal endothelial cells and astrocytes cultured on 3-D scaffolds for ocular drug discovery and development.

Topical ocular ketorolac improves the outcomes of severe retinopathy of prematurity and when administered with systemic caffeine, decreases the severity of oxygen-induced retinopathy. We tested the hypothesis that co-cultures of human retinal endothelial cells (HRECs) and human retinal astrocytes (HRAs) on 3-dimensional (3-D) hydrogel scaffolds is a more representative biomimetic paradigm of the blood-retinal-barrier (BRB) than 2-D cultures, and should be utilized for preclinical drug discovery and development. Mono- and co-cultures of HRECs and HRAs were treated with standard doses of ketorolac, ibuprofen, and/or caffeine, and exposed to hyperoxia, intermittent hypoxia (IH), or normoxia on 2-D surfaces or 3-D biodegradable hydrogel scaffolds (AlgiMatrix or Geltrex). Media and cells were collected at 72h post treatment for arachidonic acid metabolites. Cells cultured on 3-D scaffolds exhibited less oxidative stress and variability in drug responses. HRAs enhanced the responses of HRECs to drugs and changes in oxygen environment. PGE2 and PGI2 were the predominant prostanoids produced in response to IH, reflecting COX-2 immunoreactivity. We conclude that HRECs and HRAs co-cultured on 3-D scaffolds may recapitulate drug responses of the dynamic BRB and therefore should be implemented for preclinical ocular drug discovery and development.

Intermittent hypoxia alters dose dependent caffeine effects on renal prostanoids and receptors in neonatal rats.

Caffeine, one of the most commonly prescribed drugs in preterm neonates, is given in standard or suprapharmacologic doses. Although known as a diuretic, its effects in the neonatal kidneys are not well studied. We tested the hypothesis that neonatal intermittent hypoxia (IH) and high caffeine doses (HCD) alter renal regulators of vasomotor tone and water balance. Newborn rats were randomized to room air, hyperoxia, or IH and treated with standard or high caffeine doses; or placebo saline. Renal prostanoids; histopathology; and cyclooxygenase (COX), prostanoid receptor, and aquaporin (AQP) immunoreactivity were determined. HCD in IH caused severe pathological changes in the glomeruli and proximal tubules, consistent with acute kidney injury. This was associated with reductions in anthropometric growth, PGI2, and IP, DP, and AQP-4 immunoreactivity, well as a robust increase in COX-2, suggesting that the use of HCD should be avoided in preterm infants who experience frequent IH episodes.

Oxygen-Induced Retinopathy from Recurrent Intermittent Hypoxia Is Not Dependent on Resolution with Room Air or Oxygen, in Neonatal Rats.

Preterm infants often experience intermittent hypoxia (IH) with resolution in room air (RA) or hyperoxia (Hx) between events. Hypoxia is a major inducer of vascular endothelial growth factor, which plays a key role in normal and aberrant retinal angiogenesis. This study tested the hypothesis that neonatal IH which resolved with RA is less injurious to the immature retina than IH resolved by Hx between events. Newborn rats were exposed to: (1) Hx (50% O2) with brief hypoxia (12% O2); (2) RA with 12% O2; (3) Hx with RA; (4) Hx only; or (5) RA only, from P0 to P14. Pups were examined at P14 or placed in RA until P21. Retinal vascular and astrocyte integrity; retinal layer thickness; ocular and systemic biomarkers of angiogenesis; and somatic growth were determined at P14 and P21. All IH paradigms resulted in significant retinal vascular defects, disturbances in retinal astrocyte template, retinal thickening, and photoreceptor damage concurrent with elevations in angiogenesis biomarkers. These data suggest that the susceptibility of the immature retina to changes in oxygen render no differences in the outcomes between RA or O2 resolution. Interventions and initiatives to curtail O2 variations should remain a high priority to prevent severe retinopathy.

Intravitreal bevacizumab alters type IV collagenases and exacerbates arrested alveologenesis in the neonatal rat lungs.

Purpose/Aim: Intravitreal bevacizumab (Avastin) is an irreversible vascular endothelial growth factor (VEGF) inhibitor used off-label to treat severe retinopathy of prematurity in extremely low gestational age neonates. VEGF and matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs) participate in lung maturation. We tested the hypothesis that intravitreal bevacizumab enters the systemic circulation and has long-lasting effects on lung MMPs. MATERIALS AND METHODS: Neonatal rats were exposed to: (1) hyperoxia (50% O2); (2) intermittent hypoxia (IH) (50% O2 with brief episodes of 12% O2); or (3) room air (RA) from birth (P0) to P14. At P14, the time of eye opening in rats, a single dose of Avastin (0.125 mg) was injected into the vitreous cavity of the left eye. A control group received equivalent volume saline. At P23 and P45, lung MMP-2 and MMP-9, and TIMP-1, and TIMP-2 were assessed in the lungs. RESULTS: At P23, Avastin increased MMP-2, MMP-9, and TIMP-1 levels in the hyperoxia group but decreased TIMP-1 levels in the IH group. The ratios of MMP-2/TIMP-1 and MMP-9/TIMP-1 were significantly elevated at P23 in the IH group treated with Avastin. At P45, the levels of MMP-2 and MMP-9 remained elevated in the hyperoxia and IH groups treated with Avastin, while a rebound increase in TIMP-1 levels was noted in the IH group. CONCLUSIONS: Avastin treatment in IH has lasting alterations in the balance between MMPs and their tissue inhibitors. These changes may lead to impaired alveologenesis and tissue damage consistent with bronchopulmonary dysplasia/chronic lung disease.

Pharmacologic synergism of ocular ketorolac and systemic caffeine citrate in rat oxygen-induced retinopathy.

BACKGROUND: Caffeine or ketorolac decrease the risk of retinopathy of prematurity and may act synergistically to improve beneficial effect. Combination of caffeine (Caff) and ketorolac (Keto) to prevent oxygen-induced retinopathy was studied. METHODS: Newborn rats exposed to room air (RA) or intermittent hypoxia (IH) consisting of 12% O2 during hyperoxia (50% O2) from birth (P0) had single daily IP injections of Caff from P0-P13 or saline; and/or ocular Keto (Acuvail, 0.45% ophthalmic solution) administered subcutaneously over the eyes from P5-P7. Pups were studied at P14 or placed in RA for recovery from IH (IHR) until P21. Eyes were examined for neovascularization, histopathology, growth factors, and VEGF-signaling genes. RESULTS: Severe retinal damage noted during IHR in the untreated groups evidenced by hemorrhage, neovascularization, and oxygen-induced retinopathy (OIR) pathologies were prevented with Keto/Caff treatment. Keto and/or Caff treatment in IH also promoted retinal neural development evidenced by eye opening (92%, P < 0.001 vs. 31% in the placebo-treated IH group). No corneal pathologies were noted with Keto. CONCLUSION: Caff or Keto given individually reduced retinal neovascularization, but the two drugs given together prevented severe OIR.

Neonatal assessment in the delivery room--Trial to Evaluate a Specified Type of Apgar (TEST-Apgar).

BACKGROUND: Since an objective description is essential to determine infant's postnatal condition and efficacy of interventions, two scores were suggested in the past but weren't tested yet: The Specified-Apgar uses the 5 items of the conventional Apgar score; however describes the condition regardless of gestational age (GA) or resuscitative interventions. The Expanded-Apgar measures interventions needed to achieve this condition. We hypothesized that the combination of both (Combined-Apgar) describes postnatal condition of preterm infants better than either of the scores alone. METHODS: Scores were assessed in preterm infants below 32 completed weeks of gestation. Data were prospectively collected in 20 NICU in 12 countries. Prediction of poor outcome (death, severe/moderate BPD, IVH, CPL and ROP) was used as a surrogate parameter to compare the scores. To compare predictive value the AUC for the ROC was calculated. RESULTS: Of 2150 eligible newborns, data on 1855 infants with a mean GA of 28(6/7) ± 2(3/7) weeks were analyzed. At 1 minute, the Combined-Apgar was significantly better in predicting poor outcome than the Specified- or Expanded-Apgar alone. Of infants with a very low score at 5 or 10 minutes 81% or 100% had a poor outcome, respectively. In these infants the relative risk (RR) for perinatal mortality was 24.93 (13.16-47.20) and 31.34 (15.91-61.71), respectively. CONCLUSION: The Combined-Apgar allows a more appropriate description of infant's condition under conditions of modern neonatal care. It should be used as a tool for better comparison of group of infants and postnatal interventions. TRIAL REGISTRATION: clinicaltrials.gov Protocol Registration System (NCT00623038). Registered 14 February 2008.

ApTOLL: A new therapeutic aptamer for cytoprotection and (re)myelination after multiple sclerosis.

BACKGROUND AND PURPOSE: ApTOLL is an aptamer selected to antagonize toll-like receptor 4 (TLR4), a relevant actor for innate immunity involved in inflammatory responses in multiple sclerosis (MS) and other diseases. The currently available therapeutic arsenal to treat MS is composed of immunomodulators but, to date, there are no (re)myelinating drugs available in clinics. In our present study, we studied the effect of ApTOLL on different animal models of MS. EXPERIMENTAL APPROACH: The experimental autoimmune encephalomyelitis (EAE) model was used to evaluate the effect of ApTOLL on reducing the inflammatory component. A more direct effect on oligodendroglia was studied with the cuprizone model and purified primary cultures of murine and human oligodendrocyte precursor cells (OPCs) isolated through magnetic-activated cell sorting (MACS) from samples of brain cortex. Also, we tested these effects in an ex vivo model of organotypic cultures demyelinated with lysolecithin (LPC). KEY RESULTS: ApTOLL treatment positively impacted the clinical symptomatology of mice in the EAE and cuprizone models, which was associated with better preservation plus restoration of myelin and oligodendrocytes in the demyelinated lesions of animals. Restoration was corroborated on purified cultures of rodent and human OPCs. CONCLUSION AND IMPLICATIONS: Our findings reveal a new therapeutic approach for the treatment of inflammatory and demyelinating diseases such as MS. The molecular nature of the aptamer exerts not only an anti-inflammatory effect but also neuroprotective and remyelinating effects. The excellent safety profile demonstrated by ApTOLL in animals and humans opens the door to future clinical trials in MS patients.

Response of vascular endothelial growth factor and angiogenesis-related genes to stepwise increases in inspired oxygen in neonatal rat lungs.

BACKGROUND: Bronchopulmonary dysplasia is an inflammatory lung disease that afflicts preterm infants requiring supplemental oxygen and is associated with impaired pulmonary angiogenesis. We tested the hypothesis that there is a critical threshold of inspired O2 (FiO2) that alters pulmonary angiogenesis. METHODS: Within 2-6 h of birth, rat pups were exposed to 10%, 21%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% FiO2 for 2 h. Mixed arterial-venous blood gases, serum and pulmonary levels of vascular endothelial growth factor (VEGF) and soluble VEGF receptor-1, and pulmonary angiogenesis gene profiles were determined. RESULTS: PO2 increased with hyperoxia from 35.6 ± 5.0 (range: 31.5-39.8) at 10% O2 to 108.5 ± 25.0 (range: 82.2-134.8) at 100% O2. PO2 at 21% O2 was 42.4 ± 7.3 (range: 36.8-48.1). Lung VEGF levels declined at 40%-100%. The critical PO2 associated with decreased lung VEGF was 66 mm Hg, achieved with a FiO2 of 0.4. PO2 was inversely correlated with VEGF levels in the lungs (R = -0.377; P < 0.008). Antiangiogenesis genes were robustly upregulated at 70%, predominantly in males. Data are reported as mean ± SD. CONCLUSIONS: A critical threshold of FiO2 affecting angiogenesis exists in immature lungs. Exposure of preterm lungs to >40% inspired O2, even for 2 h, may result in abnormal expression of biomarkers regulating lung angiogenesis.

Carbon dots decorated magnetite nanocomposite obtained using yerba mate useful for remediation of textile wastewater through a photo-Fenton treatment: Ilex paraguariensis as a platform of environmental interest-part 2.

Two carbon dots (CD) with diameters of 4.9 ± 1.5 and 4.1 ± 1.2 nm were successfully synthesized through an acid ablation route with HNO3 or H2SO4, respectively, using Ilex paraguariensis as raw material. The CD were used to produce magnetite-containing nanocomposites through two different routes: hydrothermal and in situ. A thorough characterization of the particles by transmission electron microscopy (TEM), X-ray diffraction (XRD), thermogravimetric analysis (TGA), dynamic light scattering (DLS), Fourier transform infrared (FTIR), and X-ray photoelectron spectroscopy (XPS) indicates that all nanomaterials have spherical-like morphology with a core-shell structure. The composition of this structure depends on the route used: with the hydrothermal route, the shell is composed of the CD, but with the in situ process, the CD act as nucleation centers, and so the iron oxide domains are in the shell. Regarding the photocatalytic mechanism for the degradation of methyl orange, the interaction between the CD and the magnetite plays an important role in the photo-Fenton reaction at pH 6.2, in which ligand-to-metal charge transfer processes (LTMCT) allow Fe2+ regeneration. All materials (100 ppm) showed catalytic activity in the elimination of methyl orange (8.5 ppm), achieving discoloration of up to 98% under visible irradiation over 400 nm in 7 h. This opens very interesting possibilities for the use of agro-industrial residues for sustainable synthesis of catalytic nanomaterials, and the role of the interaction of iron-based catalysts with organic matter in heterogeneous Fenton-based processes.

Safety and effectiveness of meropenem in infants with suspected or complicated intra-abdominal infections.

BACKGROUND: Intra-abdominal infections are common in young infants and lead to significant morbidity and mortality. Meropenem is a broad-spectrum antimicrobial with excellent activity against pathogens associated with intra-abdominal infections. The purpose of this study was to determine the safety and effectiveness of meropenem in young infants with suspected or complicated intra-abdominal infections. METHODS: Preterm and term infants <91 days of age with suspected or confirmed intra-abdominal infections hospitalized in 24 neonatal intensive care units were studied in an open-label, multiple-dose study. Adverse events and serious adverse events were collected through 3 and 30 days following the last meropenem dose, respectively. Effectiveness was assessed by 3 criteria: death, bacterial cultures, and presumptive clinical cure score. RESULTS: Of 200 subjects enrolled in the study, 99 (50%) experienced an adverse event, and 34 (17%) had serious adverse events; no adverse events were probably or definitely related to meropenem. The most commonly reported adverse events were sepsis (6%), seizures (5%), elevated conjugated bilirubin (5%), and hypokalemia (5%). Only 2 of the serious adverse events were determined to be possibly related to meropenem (isolated ileal perforation and an episode of fungal sepsis). Effectiveness was evaluable in 192 (96%) subjects, and overall treatment success was 84%. CONCLUSIONS: Meropenem was well tolerated in this cohort of critically ill infants, and the majority of infants treated with meropenem met the definition of therapeutic success. CLINICAL TRIALS REGISTRATION: NCT00621192.

Iron oxide nanoparticles embedded in organic microparticles from Yerba Mate useful for remediation of textile wastewater through a photo-Fenton treatment: Ilex paraguariensis as a platform of environmental interest - Part 1.

Seven composites of iron oxide nanoparticles embedded in organic microparticles mediated by Cu(II) were synthesized using yerba mate (Ilex paraguariensis) dry leaf extract as precipitant, capping agent, and dispersant medium, using different Cu/Fe molar ratios. A thorough characterization of the particles by transmission electron microscopy (TEM), X-ray diffraction (XRD), thermogravimetric analysis-mass spectrometry (TGA-MS), Fourier transform infrared spectrometer (FTIR), and atomic absorption-spectrometry (AA) indicates that all materials have spheric-like morphology with nanoparticles composed by metal oxide phases embedded into organic microparticles. Interestingly, this organic matter is proposed to play an important role in the solids' photocatalytic activity in a photo-Fenton reaction, in which iron photo-leaching was elucidated, and a mechanism through ligand-to-metal charge transfer processes was proposed. All materials showed catalytic activity in the methyl orange elimination, achieving discolorations up to 96% in 2 h under UV irradiation at 375 nm. An experimental correlation between all samples' UV/Vis spectra and their performances for methyl orange discoloration was observed. This process opens a landscape very interesting for the use of agroindustrial residues for green synthesis of metal oxide nanomaterials and their use and understanding of organo-metallic systems participation in Fenton-based processes.

Measurement of stigma and associated characteristics in people with tuberculosis in Medellín, Colombia: a cross-sectional study.

BACKGROUND: Stigma towards tuberculosis (TB) delays diagnosis and compromises adherence to treatment. We measured the degree of stigma and identified the sociodemographic and clinical characteristics that were associated with a higher degree of stigma in patients with pulmonary and extrapulmonary TB in Colombia. METHODS: We conducted a cross-sectional study with 232 participants included in the TB control program in 2017. Sociodemographic and clinical variables were measured. The stigma component was measured through a validated scale and a multiple linear regression was used. RESULTS: The study analysed 232 patients, of which 52.2% were men, 53.5% were between 27 and 59 y of age and 66.8% had a basic-medium education level. Two characteristics were significantly related to a higher stigma score: the basic-medium education level and homeless status. Homeless status increased the stigma score by 0.27. In contrast, the adjusted stigma score decreased by 0.07 if the patient's health status was perceived as 'healthy'. CONCLUSION: Stigma is maximized in homeless patients and patients with a low education level. It is minimized in patients who perceive their state of health as 'healthy'.

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.

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.

Comparative effects of probiotics, prebiotics, and synbiotics on growth factors in the large bowel in a rat model of formula-induced bowel inflammation.

OBJECTIVES: Supplementation with probiotics has been shown to prevent gastrointestinal damage possibly through preservation of growth factors. We tested the hypothesis that probiotics, prebiotics, or synbiotics supplementation preserves intestinal insulin-like growth factors (IGFs) and epidermal growth factors (EGFs) in formula-fed neonatal rats. MATERIALS AND METHODS: At birth (postnatal day 0 [P0]), neonatal rat pups (n = 18 pups/group) were either maternally fed or hand-gavaged with formula supplemented with probiotics (Pro-Fed), prebiotics, or synbiotics from P0 to P3. A formula-fed control group received formula without supplementation. At P4, large bowel samples were assessed histologically and assayed for vascular endothelial growth factor (VEGF), soluble VEGF receptor-1, IGF-I, IGF-II, and EGF. RESULTS: All formula-fed groups were severely growth suppressed with comparable mortalities. Moderate preservation of bowel integrity was noted in the Pro-Fed group. In contrast, severe inflammation was seen in all of the other formula groups. This was associated with significant increases in VEGF levels in all of the formula groups (P < 0.05) except the Pre-Fed group. Similar elevations in soluble VEGF receptor-1 (P < 0.05), IGF-I (P < 0.05), and EGF (P < 0.05) were noted, but statistical significance was achieved only in the Pro-Fed group. CONCLUSIONS: Induction of IGF-I and EGF with moderate bowel integrity may represent a protective effect of probiotics against formula-induced inflammation. These data, taken collectively, suggest that probiotics may provide more beneficial effects on the developing large bowel than prebiotics and synbiotics.

Pharmacologic interventions for the prevention and treatment of retinopathy of prematurity.

Retinopathy of Prematurity (ROP) is a preventable neovascular retinal disease with a lifetime impact on vision and ocular morbidities. Retinal vessel immaturity and oxygen therapy, influenced or modulated by several risk factors including oxidative stress, intermittent hypoxia and desaturations, inflammation, infection, malnutrition, retinal growth factor deficiencies or excesses, and others are determinant factors of pathologic retinal angiogenesis and ROP. These factors are pharmacologic targets for prevention and/or rescue therapy. These drugs, include intravitreal anti-vascular endothelial growth factor drugs, erythropoietin, ocular propranolol, caffeine, antioxidants, insulin-like growth factor-I, and omega 3 poly-unsaturated fatty acids, and are promising therapies to prevent ROP, but require further studies. Topical ocular non-steroidal anti-inflammatory drugs (NSAIDs) target inflammatory cascade but the best, safest, and most effective ocular NSAID and formulation remain to be developed. Timing of drug intervention appears critical. Moreover, the complex interactions of the various pathophysiologic mechanisms resulting in aberrant angiogenesis thence ROP strongly suggest that drug combinations and synergisms may be required for effective prevention of ROP and a lifetime of blindness.

Impact of Low-Level Blast Exposure on Brain Function after a One-Day Tactile Training and the Ameliorating Effect of a Jugular Vein Compression Neck Collar Device.

Special Weapons and Tactics (SWAT) personnel who conduct breacher exercises are at risk for blast-related head trauma. We aimed to investigate the potential impact of low-level blast exposure during breacher training on the neural functioning of working memory and auditory network connectivity. We also aimed to evaluate the effects of a jugular vein compression collar, designed to internally mitigate slosh energy absorption, preserving neural functioning and connectivity, following blast exposure. A total of 23 SWAT personnel were recruited and randomly assigned to a non-collar (n = 11) and collar group (n = 12). All participants completed a 1-day breacher training with multiple blast exposure. Prior to and following training, 18 participants (non-collar, n = 8; collar, n = 10) completed functional magnetic resonance imaging (fMRI) of working memory using N-Back task; 20 participants (non-collar, n = 10; collar, n = 12) completed resting-state fMRI. Key findings from the working memory analysis include significantly increased fMRI brain activation in the right insular, right superior temporal pole, right inferior frontal gyrus, and pars orbitalis post-training for the non-collar group (p < 0.05, threshold-free cluster enhancement corrected), but no changes were noted for the collar group. The elevation in fMRI activation in the non-collar group was found to correlate significantly (n = 7, r = 0.943, p = 0.001) with average peak impulse amplitude experienced during the training. In the resting-state fMRI analysis, significant pre- to post-training increase in connectivity between the auditory network and two discrete regions (left middle frontal gyrus and left superior lateral occipital/angular gyri) was found in the non-collar group, while no change was observed in the collar group. These data provided initial evidence of the impact of low-level blast on working memory and auditory network connectivity as well as the protective effect of collar on brain function following blast exposure, and is congruent with previous collar findings in sport-related traumatic brain injury.

Impact of Chronic Neonatal Intermittent Hypoxia on Severity of Retinal Damage in a Rat Model of Oxygen-Induced Retinopathy.

Neonatal intermittent hypoxia (IH) followed by re-oxygenation in normoxia or supplemental oxygen (IHR) increases the risk for severe retinopathy of prematurity (ROP). The exact timing for the onset of retinal damage which may guide strategic interventions during retinal development, is unknown. We tested the hypothesis that chronic exposure of the immature retina to neonatal IH induces early manifestations of retinal damage that can be utilized as key time points for strategic pharmacologic intervention. Newborn rats were exposed to IH within 2 hours of birth (P0) until P14, or allowed to recover in room air (RA) from P14 to P21 (IHR). Retinal integrity and angiogenesis biomarkers were progressively assessed before (P0), during IH, and post IH (recovery in RA), or IHR, and compared to normoxic age-matched controls. Retinal damage occurred as early as day 3 of neonatal IH, consistent with vascular abnormalities and disturbances in the astrocytic template. These abnormalities worsened during IHR. Pharmacologic and non-pharmacologic interventions to identify, prevent, or minimize neonatal IH should be implemented shortly after birth in high risk preterm newborns. This strategy may lead to a reduction in the outcome of severe ROP requiring later invasive treatments.