Peripheral neuropathy, an independent risk factor for falls in the elderly, impairs stepping as a postural control mechanism: A case-cohort study.

BACKGROUND/AIMS: Peripheral neuropathies perturbate the sensorimotor system, causing difficulties in walking-related motor tasks and, eventually, falls. Falls result in functional dependency and reliance on healthcare, especially in older persons. We investigated if peripheral neuropathy is a genuine risk factor for falls in the elderly and if quantification of postural control via posturography is helpful in identifying subjects at risk of falls. METHODS: Seventeen older persons with a clinical polyneuropathic syndrome of the lower limbs and converging electrophysiology were compared with 14 older persons without polyneuropathy. All participants were characterized via quantitative motor and sensory testing, neuropsychological assessment, and self-questionnaires. Video-nystagmography and caloric test excluded vestibulocochlear dysfunction. For further analysis, all subjects were stratified into fallers and non-fallers. Overall, 28 patients underwent computerized dynamic posturography for individual fall risk assessment. Regression analyses were performed to identify risk factors and predictive posturography parameters. RESULTS: Neuropathy is an independent risk factor for falls in the elderly, while no differences were observed for age, gender, weight, frailty, DemTect test, timed "Up & Go" test, and dizziness-related handicap score. In computerized dynamic posturography, fallers stepped more often to regain postural control in challenging conditions, while the Rhythmic Weight Shift test showed a lack of anterior-posterior bidirectional voluntary control. INTERPRETATION: Our study confirms peripheral neuropathy as a risk factor for older persons' falls. Fallers frequently used stepping to regain postural control. The voluntary control of this coping movement was impaired. Further investigations into these parameters' value in predicting the risk of falls in the elderly are warranted.

Biotransformation modulates the penetration of metallic nanomaterials across an artificial blood-brain barrier model.

Understanding the potential of nanomaterials (NMs) to cross the blood-brain barrier (BBB), as a function of their physicochemical properties and subsequent behavior, fate, and adverse effect beyond that point, is vital for evaluating the neurological effects arising from their unintentional entry into the brain, which is yet to be fully explored. This is not only due to the complex nature of the brain but also the existing analytical limitations for characterization and quantification of NMs in the complex brain environment. By using a fit-for-purpose analytical workflow and an in vitro BBB model, we show that the physiochemical properties of metallic NMs influence their biotransformation in biological matrices, which in turn modulates the transport form, efficiency, amounts, and pathways of NMs through the BBB and, consequently, their neurotoxicity. The data presented here will support in silico modeling and prediction of the neurotoxicity of NMs and facilitate the tailored design of safe NMs.

Association of Early Life Prescriptions for Antibiotics and Acid Suppressants with Childhood Psychotropic Prescriptions.

OBJECTIVE: To examine the association between antibiotic and acid suppressant prescriptions in the first 2 years of life and subsequent treatment for childhood psychiatric disorders. STUDY DESIGN: This was a retrospective cohort study of children born between October 2001 and September 2012 in the Military Health System enrolled in TRICARE past age 2 years and within 35 days of birth, with an initial hospital stay <7 days, and without psychotropic agents dispensed during the first 2 years of life. Exposure was defined as a filled prescription for an antibiotic or acid suppressant before age 2 years, and the outcome was defined as a filled prescription for a psychotropic agent after age 2 years. RESULTS: For the 804 920 patients (51% males and 49% female) composing the study population, the mean age at first psychotropic prescription was 6.8 years. A total of 24 176 children (3%) were prescribed a proton pump inhibitor (PPI), 79 243 (10%) were prescribed a histamine-2 receptor antagonist (H2RA), and 607 348 (76%) were prescribed an antibiotic during the first 2 years of life. The adjusted hazard ratio (aHR) of a psychotropic prescription was significantly increased in children prescribed any H2RA (1.79; 95% CI, 1.63-1.96), PPI (1.47; 95% CI, 1.26-1.71), or antibiotic (1.71; 95% CI, 1.59-1.84). The aHR of psychotropic prescriptions increased commensurately with each additional antibiotic class added and with each additional class of medication (H2RA, PPI, or antibiotics) prescribed. CONCLUSIONS: Children prescribed antibiotic and acid suppressants in the first 2 years of life have a significant increase in future prescriptions for psychotropics, with a dose-related effect observed. This association represents a potential risk of early exposure to antibiotics and acid suppressants.

An Untargeted Thermogravimetric Analysis-Fourier Transform Infrared-Gas Chromatography-Mass Spectrometry Approach for Plastic Polymer Identification.

Reliable chemical identification of specific polymers in environmental samples represents a major challenge in plastic research, especially with the wide range of commercial polymers available, along with variable additive mixtures. Thermogravimetric analysis-Fourier transform infrared-gas chromatography-mass spectrometry (TGA-FTIR-GC-MS) offers a unique characterization platform that provides both physical and chemical properties of the analyzed polymers. This study presents a library of 11 polymers generated using virgin plastics and post-consumer products. TGA inflection points and mass of remaining residues following pyrolysis, in some cases, proved to be indicative of the polymer type. FTIR analysis of the evolved gas was able to differentiate between all but polypropylene (PP) and polyethylene (PE). Finally, GC-MS was able to differentiate between the unique chemical fingerprints of all but one polymer in the library. This library was then used to characterize real environmental samples of mesoplastics collected from beaches in the U.K. and South Africa. Unambiguous identification of the polymer types was achieved, with PE being the most frequently detected polymer and with South African samples indicating variations that potentially resulted from aging and weathering.

Antibiotic and acid-suppression medications during early childhood are associated with obesity.

OBJECTIVE: Gut microbiota alterations are associated with obesity. Early exposure to medications, including acid suppressants and antibiotics, can alter gut biota and may increase the likelihood of developing obesity. We investigated the association of antibiotic, histamine-2 receptor antagonist (H2RA) and proton pump inhibitor (PPI) prescriptions during early childhood with a diagnosis of obesity. DESIGN: We performed a cohort study of US Department of Defense TRICARE beneficiaries born from October 2006 to September 2013. Exposures were defined as having any dispensed prescription for antibiotic, H2RA or PPI medications in the first 2 years of life. A single event analysis of obesity was performed using Cox proportional hazards regression. RESULTS: 333 353 children met inclusion criteria, with 241 502 (72.4%) children prescribed an antibiotic, 39 488 (11.8%) an H2RA and 11 089 (3.3%) a PPI. Antibiotic prescriptions were associated with obesity (HR 1.26; 95% CI 1.23 to 1.28). This association persisted regardless of antibiotic class and strengthened with each additional class of antibiotic prescribed. H2RA and PPI prescriptions were also associated with obesity, with a stronger association for each 30-day supply prescribed. The HR increased commensurately with exposure to each additional medication group prescribed. CONCLUSIONS: Antibiotics, acid suppressants and the combination of multiple medications in the first 2 years of life are associated with a diagnosis of childhood obesity. Microbiota-altering medications administered in early childhood may influence weight gain.

Using Variable Ionization Energy Time-of-Flight Mass Spectrometry with Comprehensive GC×GC To Identify Isomeric Species.

Although GC×GC-ToF-MS allows the separation of thousands of peaks, many of these peaks are not positively identified owing to the lack of mass spectral library data and/or standard materials, leading to a substantial amount of information being inaccessible. The fragmentation patterns of molecules in mass spectrometers using electron impact ionization at 70 eV can be useful for molecule identification, provided a match is available in a published EI MS library, but are indistinguishable for many isomeric organic compounds (for example, linear and branched alkanes). Lower ionization energies have been exploited leading to organic compounds being ionized with lower excess internal energy and less fragmentation, retaining the molecular ion and maximizing its relative signal. This has enabled the identification of a large number of isomeric organic compounds, both aliphatic and aromatic, between C12-C36, in the previously unresolved complex mixture (UCM) of two motor oil samples. This technique also demonstrates problems associated with separation of coeluting isomers, particularly for the n-alkanes, which are routinely measured by 1D GC/MS and may be overestimated, due to coelution. As a consequence retention times in 2 dimensions and mass spectra at variable ionization energies are shown to give unparalleled power to identify specific isomers.

The characterisation of diesel exhaust particles - composition, size distribution and partitioning.

A number of major research questions remain concerning the sources and properties of road traffic generated particulate matter. A full understanding of the composition of primary vehicle exhaust aerosol and its contribution to secondary organic aerosol (SOA) formation still remains elusive, and many uncertainties exist relating to the semi-volatile component of the particles. Semi-Volatile Organic Compounds (SVOCs) are compounds which partition directly between the gas and aerosol phases under ambient conditions. The SVOCs in engine exhaust are typically hydrocarbons in the C15-C35 range, and are largely uncharacterised because they are unresolved by traditional gas chromatography, forming a large hump in the chromatogram referred to as Unresolved Complex Mixture (UCM). In this study, thermal desorption coupled to comprehensive Two Dimensional Gas-Chromatography Time-of-Flight Mass-Spectrometry (TD-GC × GC-ToF-MS) was exploited to characterise and quantify the composition of SVOCs from the exhaust emission. Samples were collected from the exhaust of a diesel engine, sampling before and after a diesel oxidation catalyst (DOC), while testing at steady state conditions. Engine exhaust was diluted with air and collected using both filter and impaction (nano-MOUDI), to resolve total mass and size resolved mass respectively. Adsorption tubes were utilised to collect SVOCs in the gas phase and they were then analysed using thermal desorption, while particle size distribution was evaluated by sampling with a DMS500. The SVOCs were observed to contain predominantly n-alkanes, branched alkanes, alkyl-cycloalkanes, alkyl-benzenes, PAHs and various cyclic aromatics. Particle phase compounds identified were similar to those observed in engine lubricants, while vapour phase constituents were similar to those measured in fuels. Preliminary results are presented illustrating differences in the particle size distribution and SVOCs composition when collecting samples with and without a DOC. The results indicate that the DOC tested is of very limited efficiency, under the studied engine operating conditions, for removal of SVOCs, especially at the upper end of the molecular weight range.

Altered leukotriene B4 metabolism in CYP4F18-deficient mice does not impact inflammation following renal ischemia.

Inflammatory responses to infection and injury must be restrained and negatively regulated to minimize damage to host tissue. One proposed mechanism involves enzymatic inactivation of the pro-inflammatory mediator leukotriene B4, but it is difficult to dissect the roles of various metabolic enzymes and pathways. A primary candidate for a regulatory pathway is omega oxidation of leukotriene B4 in neutrophils, presumptively by CYP4F3A in humans and CYP4F18 in mice. This pathway generates ω, ω-1, and ω-2 hydroxylated products of leukotriene B4, depending on species. We created mouse models targeting exons 8 and 9 of the Cyp4f18 allele that allows both conventional and conditional knockouts of Cyp4f18. Neutrophils from wild-type mice convert leukotriene B4 to 19-hydroxy leukotriene B4, and to a lesser extent 18-hydroxy leukotriene B4, whereas these products were not detected in neutrophils from conventional Cyp4f18 knockouts. A mouse model of renal ischemia-reperfusion injury was used to investigate the consequences of loss of CYP4F18 in vivo. There were no significant changes in infiltration of neutrophils and other leukocytes into kidney tissue as determined by flow cytometry and immunohistochemistry, or renal injury as assessed by histological scoring and measurement of blood urea nitrogen. It is concluded that CYP4F18 is necessary for omega oxidation of leukotriene B4 in neutrophils, and is not compensated by other CYP enzymes, but loss of this metabolic pathway is not sufficient to impact inflammation and injury following renal ischemia-reperfusion in mice.

Association of prematurity with the development of infantile hypertrophic pyloric stenosis.

BACKGROUND: Infantile hypertrophic pyloric stenosis (IHPS) has several known risk factors. The association between prematurity and IHPS and the timeline of presentation are poorly defined. Our aim was to evaluate the associations between IHPS and prematurity. METHODS: We performed a retrospective cohort study of 1,074,236 children born between June 2001 and April 2012 in the US Military Health System. IHPS cases and gestational ages (GA) were identified using billing codes. Additional risk factors for IHPS were controlled for in a multivariable logistic regression model. RESULTS: The incidence of IHPS was 2.99 per 1,000 in preterm infants and 2.25 per 1,000 in full term (relative risk (RR) = 1.33, 95% confidence interval (CI) 1.16-1.54). The adjusted odds ratio for prematurity was 1.26 (95% CI 1.08-1.46). The median (interquartile range (IQR)) chronological age at presentation was 40 d (30-56) in preterm infants vs. 33 d (26-45) in full term (P < 0.001). Median postmenstrual age at presentation was 42 wk in preterm infants (40-42) vs. 45 wk (44-46) in full term (P < 0.001). CONCLUSION: Prematurity is associated with IHPS. Premature infants develop IHPS at a later chronological age, but earlier postmenstrual age, than term infants. Providers should have an increased concern for IHPS development in premature infants.

Urinary metabolites of polycyclic aromatic hydrocarbons in Saudi Arabian schoolchildren in relation to sources of exposure.

Polycyclic aromatic hydrocarbons contain a number of known carcinogenic compounds, and urinary biomarkers have been widely used as a measure of exposure but quantitative relationships with exposure variables have proved elusive. This study aimed to quantify the relationship between exposures to phenanthrene and pyrene from atmospheric and dietary sources with the excretion of 1-hydroxypyrene and hydroxyphenanthrenes in urine as biomarkers of exposure. The study population consisted of 204 male schoolchildren attending three schools in different parts of Jeddah, Saudi Arabia who provided urine samples on each of three consecutive days. Outdoor air measurements of polycyclic aromatic hydrocarbons were made at the schools and the children provided information on diet, exposure to environmental tobacco smoke and incense, and various lifestyle factors through a questionnaire. Mixed models with random effects for subjects nested within site were fitted in order to examine the relationship between exposure variables and urinary PAH metabolites. A unit increase (1 ng m(-3)) in ambient pyrene (particulate plus gaseous phase) was associated with a 3.5% (95% CI: 1.01%, 5.13%) increase in urinary 1-hydroxypyrene concentration. A unit increase in ambient phenanthrene was associated with a 1.01% (95% CI: 0.03%, 2.02%) increase in total hydroxyphenanthrene concentrations. Consumption of chargrilled food increased the 1-hydroxypyrene and hydroxyphenanthrene concentrations by 24% (95% CI: 11%, 37%) and 17% (95% CI: 8%, 26%) respectively. We did not find evidence of association for environmental tobacco smoke exposure or incense burning. It is concluded that both respiratory exposure and consumption of chargrilled food are considerable sources of PAH exposure in this population as reflected by concentrations of urinary biomarkers.

Use of a versatile high efficiency multiparallel denuder for the sampling of PAHs in ambient air: gas and particle phase concentrations, particle size distribution and artifact formation.

The design and performance of a multiparallel plate denuder able to operate at low and high-flow (3-30 L/min) for the collection of polycyclic aromatic hydrocarbon (PAH) vapor is described. The denuder, in combination with a micro orifice uniform deposit impactor (MOUDI) was used to assess processes of artifact formation in MOUDIs used with and without an upstream denuder. Duplicate sampling trains with an upstream denuder showed good repeatability of the measured gas and particle-phase concentrations and low breakthrough in the denuder (3.5-15%). The PAH size distributions within undenuded and denuded MOUDIs were studied. Use of the denuder altered the measured size distribution of PAHs toward smaller sizes, but both denuded and undenuded systems are subject to sampling artifacts.

Maternal and Fetal Health Risks Among Female Military Aviation Officers.

INTRODUCTION: Military aviation poses unique occupational risks, including exposures to intermittent hypoxia, high gravitational force, and toxic materials, in addition to circadian disruption, cosmic radiation, and ergonomic stressors also present in commercial flight. We sought to investigate whether a military aviation officer's career is associated with adverse maternal or fetal health outcomes.METHODS: We conducted a retrospective cohort study of female aviation and nonaviation officers in the Military Health System from October 2002 to December 2019. Exposure was identified as assignment of an aviation occupation code. Maternal and fetal health outcomes were identified by International Classification of Diseases codes from medical records. Regression analysis was used to estimate adjusted relative risks (aRR).RESULTS: Included in the study were 25,929 active-duty female officers, with 46,323 recorded pregnancies and 32,853 recorded deliveries; 2131 pregnancies were diagnosed in aviation officers. Pregnant aviation officers had a decreased risk of composite adverse pregnancy outcomes [aRR 0.82 (0.73-0.92)], including gestational diabetes [aRR 0.69 (0.57-0.85)] and gestational hypertension [aRR 0.84 (0.71-0.99)]. Pregnant aviation officers had a decreased risk of depression prior to delivery [aRR 0.43 (0.35-0.53)] and hyperemesis gravidarum [aRR 0.74 (0.57-0.96)], but an increased risk of placental complications [aRR 1.15 (1.02-1.30)] and fetal growth restriction [aRR 1.36 (1.16-1.60)].DISCUSSION: Pregnant military aviation officers have an increased risk of placental complications and fetal growth restriction in spite of a lower risk of gestational diabetes and gestational hypertension. Further research is needed to determine how flight-related occupations impact pregnancy.Stark CM, Sorensen IS, Royall M, Dorr M, Brown J, Dobson N, Salzman S, Susi A, Hisle-Gorman E, Huggins BH, Nylund CM. Maternal and fetal health risks among female military aviation officers. Aerosp Med Hum Perform. 2024; 95(9):675-682.

New frontiers in neonatal red blood cell transfusion research.

Red blood cell (RBC) transfusions are common in neonates requiring intensive care. Recent studies have compared restricted versus liberal transfusion guidelines, but limitations exist on evaluations of outcomes in populations that never required a transfusion compared to those receiving any transfusion. Although there are well-established risks associated with RBC transfusions, new data has emerged that suggests additional clinically relevant associations, including adverse neurodevelopmental outcomes, donor sex differences, and inflammation or immunosuppression. Further research is needed to delineate the magnitude of these risks and to further improve the safety of transfusions. The goal of this review is to highlight underappreciated, yet clinically important risks associated with neonatal RBC transfusions and to introduce several areas in which neonates may uniquely benefit from alterations in practice.

Massive fetomaternal haemorrhage warranting novel use of tandem isovolumetric partial exchange transfusion and therapeutic hypothermia.

A newborn male infant was pale, hypotonic, and had respiratory distress after delivery. Venous cord blood gas revealed a severe metabolic acidosis. His initial examination was consistent with moderate encephalopathy and laboratory testing uncovered severe congenital anaemia (haematocrit 0.127 L/L). He met the clinical criteria for therapeutic hypothermia (TH) and required red blood cell transfusions, but due to the severity of his anaemia, an exchange transfusion was favoured to prevent transfusion-associated circulatory overload. There are no previous reports of these procedures completed in tandem, but the benefits were perceived to outweigh the risks. During the 72 hours of TH, the infant received an isovolumetric partial exchange transfusion and tolerated both treatments without any adverse clinical events.Kleihauer-Betke testing detected a massive chronic fetomaternal haemorrhage with 475 mL (164 mL/kg) of blood. A brain MRI completed prior to discharge was normal. At 6 months of age, he is growing and developing normally.

Validation of an optimised microwave-assisted acid digestion method for trace and ultra-trace elements in indoor PM2.5 by ICP-MS analysis.

Three microwave-assisted digestion procedures, followed by analysis of digestates employing inductively coupled mass spectrometry (ICP-MS) were evaluated for use in the determination of elements at trace and ultra-trace levels in PM2.5 samples. Digestion procedure 1 used 2.5 mL HNO3 (65%) at 200 °C. Procedure 2, consisted of a two-stage digestion step at 200 °C with 2.5 mL HNO3 (65%) and 3 µL HF (48%) followed by 24 µL H3BO3 (5%). A 10-fold increase in the amounts of HF and H3BO3 was used for procedure 3. The addition of HF/H3BO3 was carried out to aid the dissolution of silicate matrices and refractory compounds. The digestions were carried out using PTFE ultra-trace inserts which increased the sample throughput threefold. The addition of small quantities of HF resulted in the effective solubilisation of Na, Mg, Al, K, Ca, Ti, V, Cr, Mn, Fe, Ni, Cu, Zn, As, Sr, Cd, Sb and Pb. The optimal method using HNO3/HF/H3BO3 digestion as in procedure 3 showed recovery efficiency greater than 70% for all elements. The validated method was applied to quantify the elemental content of indoor and outdoor PM2.5 (with samples <0.5 mg) at an urban background site in Malta.

Chest Pain and Fever in a Healthcare Provider During the Global Coronavirus Pandemic.

The coronavirus disease 2019 (COVID-19) global pandemic has posed unique challenges to healthcare providers that work in austere environments. Military healthcare providers advise commanders on endemic disease risk, prevention, and management during field training exercises. Healthcare workers are at increased risk of exposure to infectious pathogens. We present a case of a military healthcare provider who presented with fever, cough, and fatigue during the COVID-19 global pandemic that was diagnosed with a primary pulmonary coccidioidal infection. Treatment after appropriate diagnosis consisted of supportive care. Respiratory and pain symptoms resolved by 2 months post-diagnosis. Although COVID-19 must be closely monitored in the field training environment, it is important to maintain a high index of suspicion of endemic infectious diseases as a potential etiology for respiratory illnesses.

Formulation of inherently antimicrobial magnesium oxychloride cement and the effect of supplementation with silver phosphate.

The growing threat of bacterial resistance to antibiotics is driving an increasing need for new antimicrobial strategies. This work demonstrates the potential of magnesium oxychloride cements (MOC) to be used as inorganic antimicrobial biomaterials for bone augmentation. An injectable formulation was identified at a powder to liquid ratio of 1.4 g mL-1, with an initial setting time below 30 mins and compressive strength of 35 ± 9 MPa. Supplementation with Ag3PO4 to enhance the antimicrobial efficacy of MOC was explored, and shown via real time X-ray diffraction to retard the formation of hydrated oxychloride phases by up to 30%. The antimicrobial efficacy of MOC was demonstrated in vitro against Staphylococcus aureus and Pseudomonas aeruginosa, forming zones of inhibition and significantly reducing viability in broth culture. Enhanced efficacy was seen for silver doped formulations, with complete eradication of detectable viable colonies within 3 h, whilst retaining the cytocompatibility of MOC. Investigating the antimicrobial mode of action revealed that Mg and Ag release and elevated pH contributed to MOC efficacy. Sustained silver release was demonstrated over 14 days, suggesting the Ag3PO4 modified formulation offers two mechanisms of infection treatment, combining the inherent antimicrobial properties of MOC with controlled release of inorganic antimicrobials.

Behaviour of traffic emitted semi-volatile and intermediate volatility organic compounds within the urban atmosphere.

Particulate matter originated from traffic has attracted major interest over the last few years. The semi-volatile organic component of the particles may evaporate with dispersion away from the emission source, creating vapour which may oxidise to form secondary organic aerosol. Air samples were collected from a street canyon, the adjacent park and an urban background site during the winter-spring period in central London, UK. Emissions of semi-volatile organic compounds (SVOCs) and intermediate volatility organic compounds (IVOCs) ranging from C10 to C36 in both the gas phase and particle phase were measured by using thermal desorption coupled to comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (TD-GC × GC-ToF-MS). Main compound groups identified and quantified were grouped alkanes (n-alkanes and branched alkanes), monocyclic alkanes, bicyclic alkanes and monocyclic aromatics. The carbon preference index (CPI) of n-alkanes was estimated to distinguish the emission sources. Pearson correlations between I/SVOCs and traffic tracers (black carbon, NOx and benzene) in different locations were compared to analyse the influence of this emission source. The results indicate that while the major emission source at the roadside site is traffic, the lower correlations at background sites are indicative of other source contributions and/or differential reactivity of compounds. Gas-particle phase partitioning of n-alkanes is evaluated and compared between sites. The potential influence of gas phase I/SVOCs upon OH reactivity and secondary organic aerosol (SOA) formation is estimated and found to be relatively small.

Percutaneous Biliary Endoscopy for Stones.

Intraductal biliary stones can result in significant acute and long-term complications. When patients' anatomy precludes more traditional management, the interventional radiologist may be called upon to provide well-established techniques for percutaneous biliary drainage and stone removal. This can be particularly challenging when the patient has excessively mobile, impacted, large or multiple stones. Percutaneous biliary endoscopy with adjunct interventional techniques can successfully treat these patients avoiding the patient dreaded "tube for life" scenario. Direct percutaneous visualization of the biliary tree can also diagnose and provide symptomatic relief for stone-mimicking pathologic conditions such as biliary tumors. This article will review the role, technique, and considerations for percutaneous biliary endoscopy and adjunct interventions in patients with isolated and complex, biliary stone disease and stone-mimicking pathologies.