Current obstetric outcomes in Jamaican women with sickle hemoglobinopathy - a balance of risks for aspirin?

OBJECTIVES: Sickle cell disease (SCD) occurs in 2.8 % of our Jamaican antenatal population with homozygous HbSS being most associated with adverse maternal and perinatal outcomes. METHODS: A retrospective comparative analysis of HbSS, HbSC and HbSßThal pregnancy outcomes at the University Hospital of the West Indies (UHWI) between January 2012 and December 2022 was conducted. RESULTS: Of 120 patients (138 pregnancies), obesity occurred in 36 % (20/56) of the 'non-HbSS' group, i.e. HbSßThal (55 %, 5/9) and HbSC (32 %, 15/47) combined vs. 9.7 % of the HbSS (8/82). HbSS patients had more crises requiring transfusions, acute chest syndrome (ACS), maternal 'near-misses' (OR=10.7, 95 % 3.5-32.3; p<0.001), hospitalizations (OR 7.6, 95 % CI 3.4-16.9; p<0.001), low birth weight (LBW) neonates (OR 3.1, 1.1-8.9; p=0.037) and preterm birth (OR=2.6, 1.2-5.8; p=0.018) compared to HbSC and HbSßThal. Low dose aspirin was prescribed in 43 %. Logistic regression showed those NOT on aspirin (n=76) had more miscarriages (22 v. 2 %), were LESS likely to have a live birth (75 v. 95 % (0.2, 0.04-0.57, p=0.005)), but surprisingly had fewer painful crises (28 v. 46 % (0.5, 0.03-0.9, p=0.03)). CONCLUSIONS: HbSS women had a 10-fold excess of maternal near-misses. Additional research may further clarify the effects of aspirin on pregnancy outcomes as related to SCD genotypes.

A Quality Improvement Evaluation of a Primary As-Needed Light Sedation Protocol in Mechanically Ventilated Adults.

OBJECTIVES: First, to implement successfully a light-sedation protocol, favoring initial as-needed (prioritizing as-needed) boluses over continuous infusion sedation, and second, to evaluate if this protocol was associated with differences in patient-level sedative requirements, clinical outcomes, and unit-level longitudinal changes in pharmacy charges for sedative medications. DESIGN: Retrospective review comparing patients who received the prioritizing as-needed sedation protocol to similar patients eligible for the prioritizing as-needed protocol but treated initially with continuous infusion sedation. SETTING: Thirty-two bed medical ICUs in a large academic medical center. PATIENTS: A total of 254 mechanical ventilated patients with a target Riker Sedation-Agitation Scale goal of 3 or 4 were evaluated over a 2-year period. Of the evaluable patients, 114 received the prioritizing as-needed sedation protocol and 140 received a primary continuous infusion approach. INTERVENTIONS: A multidisciplinary leadership team created and implemented a light-sedation protocol, focusing on avoiding initiation of continuous sedative infusions and prioritizing prioritizing as-needed sedation. MEASUREMENTS AND MAIN RESULTS: Overall, 42% of patients in the prioritizing as-needed group never received continuous infusion sedation. Compared with the continuous infusion sedation group, patients treated with the prioritizing as-needed protocol received significantly less opioid, propofol, and benzodiazepine. Patients in the prioritizing as-needed group experienced less delirium, shorter duration of mechanical ventilation, and shorter ICU length of stay. Adverse events were similar between the two groups. At the unit level, protocol implementation was associated with reductions in the use of continuous infusion sedative medications. CONCLUSIONS: Implementation and use of a prioritizing as-needed protocol targeting light sedation appear to be safe and effective. These single-ICU retrospective findings require wider, prospective validation.

Effects of propofol on ischemia-reperfusion and traumatic brain injury.

Oxidative stress exacerbates brain damage following ischemia-reperfusion and traumatic brain injury (TBI). Management of TBI and critically ill patients commonly involves use of propofol, a sedation medication that acts as a general anesthetic with inherent antioxidant properties. Here we review available evidence from animal model systems and clinical studies that propofol protects against ischemia-reperfusion injury. However, evidence of propofol toxicity in humans exists and manifests as a rare complication, "propofol infusion syndrome" (PRIS). Evidence in animal models suggests that brain injury induces expression of the p75 neurotrophin receptor (p75NTR), which is associated with proapoptotic signaling. p75NTR-mediated apoptosis of neurons is further exacerbated by propofol's superinduction of p75NTR and concomitant inhibition of neurotrophin processing. Propofol is toxic to neurons but not astrocytes, a type of glial cell. Evidence suggests that propofol protects astrocytes from oxidative stress and stimulates astroglial-mediated protection of neurons. One may speculate that in brain injury patients under sedation/anesthesia, propofol provides brain tissue protection or aids in recovery by enhancing astrocyte function. Nevertheless, our understanding of neurologic recovery versus long-term neurological sequelae leading to neurodegeneration is poor, and it is also conceivable that propofol plays a partial as yet unrecognized role in long-term impairment of the injured brain.

Universal Anesthesia Machine: Clinical Application in an Austere, Resource-Limited Environment.

INTRODUCTION: In austere environments, the safe administration of anesthesia becomes challenging because of unreliable electrical sources, limited amounts of compressed gas, and insufficient machine maintenance capabilities. Such austere environments exist in battlefield medicine, in low- and middle-income countries (LMICs), and in areas struck by natural disasters. Whether in military operations or civilian settings, the Universal Anesthesia Machine (UAM) (Gradian Health Systems, New York, New York) is a draw-over device capable of providing safe and effective general anesthesia when external oxygen supplies or reliable electrical sources are limited. This brief report discusses a proof-of-concept observational study demonstrating the clinical utility of the UAM in a resource-limited area. MATERIALS AND METHODS: This observational study of 20 patients in Haiti who underwent general anesthesia using the UAM highlights the device's capability to deliver anesthesia intraoperatively in a resource-limited LMIC clinical setting. Preoxygenation was achieved with the UAM's draw-over oxygen supply. Patients received acetaminophen for analgesia, dexmedetomidine for preinduction anesthesia, and succinylcholine for paralysis. After induction, the UAM provided a mixture of oxygen and isoflurane for maintenance of anesthesia. Manual ventilation was performed using draw-over bellows until spontaneous ventilation recurred, when clinically appropriate, artificial airways were removed. Intraoperative medication was administered at the anesthesiologist's discretion. The institutional review board at the U.S. anesthesiologists' affiliated institution and the Haitian hospital approved this study; patients were consented in their native language. RESULTS: Two anesthesiologists used the UAM to deliver general anesthesia to 20 patients in a Haitian hospital without access to an external oxygen supply, reliable power grid, or opioids. The patients' average age was ~40 years, and 90% of them were male. Most of the cases were herniorrhaphy (50%) and hydrocelectomy (25%) surgeries. The median American Society of Anesthesiologists (ASA) score was 2; 45% of the patients had an ASA score of 1, and none had an ASA score >3. Of the 20 cases, 55% of patients received an endotracheal tube, and 40% received a laryngeal mask airway; for one patient, only a masked airway was used. Every patient was discharged on the day of the surgery. No complications occurred in the perioperative or 1-month follow-up period. CONCLUSION: The UAM can be used where a lack of resources and training exist because of its simple design, built-in oxygen concentrator, and capacity to revert from continuous-flow to draw-over anesthesia in the event of a power failure or if external oxygen supplies are unavailable. We believe the UAM addresses some of the shortcomings of modern anesthesia machines and has the potential to improve the delivery of safe general anesthesia in combat and austere scenarios. Further studies could consider different types of surgeries than those reported here and involve more complex patients. Studies involving alternative anesthetic agents and non-anesthesiologist personnel are also needed. Overall, this brief report detailing the use of the UAM following a natural disaster in a LMIC is proof of concept that the machine can provide reliable anesthesia for surgical procedures in austere and resource-limited environments, including disaster areas and modern combat zones.

Frequency of kdr and kdr-his Alleles in Stable Fly (Diptera: Muscidae) Populations From the United States, Costa Rica, France, and Thailand.

Anecdotal evidence of pyrethroid insecticide product failure for the control of stable fly [Stomoxys calcitrans (L.)] populations in the United States and worldwide prompted us to evaluate the frequency of knockdown resistance (kdr)-type polymorphisms within the voltage-sensitive sodium channel (Vssc) gene of field collected specimens from the United States, France, Costa Rica, and Thailand. The kdr-his allele (L1014H), associated with permethrin resistance, was detected in stable flies from the 10 states sampled in the United States, as well as from Costa Rica and France (Toulouse). Field collections of stable flies from California (Modesto) and New York (Cliffton Springs) exhibited reduced susceptibility upon exposure to a diagnostic permethrin concentration of 10× LC99, but survival did not appear to strictly associate with frequency of the kdr-his allele. This suggests that there are additional resistance mechanisms contributing to the phenotype in these states. The kdr allele (L1014F) was detected for the first time in stable flies originating in France and Thailand, and an improved, DNA-based diagnostic assay was developed and validated for use in future screens for kdr and kdr-his allele frequencies from field collections. The absence of kdr in United States and Costa Rica populations suggests that the allele is currently restricted to Europe and Asia.

A rapid method for assessing the accumulation of microplastics in the sea surface microlayer (SML) of estuarine systems.

Microplastics are an increasingly important contaminant in the marine environment. Depending on their composition and degree of biofouling, many common microplastics are less dense than seawater and so tend to float at or near the ocean surface. As such, they may exhibit high concentrations in the sea surface microlayer (SML - the upper 1-1000 µm of the ocean) relative to deeper water. This paper examines the accumulation of microplastics, in particular microfibres, in the SML in two contrasting estuarine systems - the Hamble estuary and the Beaulieu estuary, southern U.K., via a novel and rapid SML-selective sampling method using a dipped glass plate. Microplastic concentrations (for identified fibres, of 0.05 to 4.5 mm length) were highest in the SML-selective samples (with a mean concentration of 43 ± 36 fibres/L), compared to <5 fibres/L for surface and sub-surface bulk water samples. Data collected show the usefulness of the dipped glass plate method as a rapid and inexpensive tool for sampling SML-associated microplastics in estuaries, and indicate that microplastics preferentially accumulate at the SML in estuarine conditions (providing a potential transfer mechanism for incorporation into upper intertidal sinks). Fibres are present (and readily sampled) in both developed and more pristine estuarine systems.

TonB-Dependent Heme/Hemoglobin Utilization by Caulobacter crescentus HutA.

Siderophore nutrition tests with Caulobacter crescentus strain NA1000 revealed that it utilized a variety of ferric hydroxamate siderophores, including asperchromes, ferrichromes, ferrichrome A, malonichrome, and ferric aerobactin, as well as hemin and hemoglobin. C. crescentus did not transport ferrioxamine B or ferric catecholates. Because it did not use ferric enterobactin, the catecholate aposiderophore was an effective agent for iron deprivation. We determined the kinetics and thermodynamics of [59Fe]apoferrichrome and 59Fe-citrate binding and transport by NA1000. Its affinity and uptake rate for ferrichrome (equilibrium dissociation constant [Kd ], 1 nM; Michaelis-Menten constant [KM ], 0.1 nM; Vmax, 19 pMol/109 cells/min) were similar to those of Escherichia coli FhuA. Transport properties for 59Fe-citrate were similar to those of E. coli FecA (KM , 5.3 nM; Vmax, 29 pMol/109 cells/min). Bioinformatic analyses implicated Fur-regulated loci 00028, 00138, 02277, and 03023 as TonB-dependent transporters (TBDT) that participate in iron acquisition. We resolved TBDT with elevated expression under high- or low-iron conditions by SDS-PAGE of sodium sarcosinate cell envelope extracts, excised bands of interest, and analyzed them by mass spectrometry. These data identified five TBDT: three were overexpressed during iron deficiency (00028, 02277, and 03023), and 2 were overexpressed during iron repletion (00210 and 01196). CLUSTALW analyses revealed homology of putative TBDT 02277 to Escherichia coli FepA and BtuB. A Δ02277 mutant did not transport hemin or hemoglobin in nutrition tests, leading us to designate the 02277 structural gene as hutA (for heme/hemoglobin utilization).IMPORTANCE The physiological roles of the 62 putative TBDT of C. crescentus are mostly unknown, as are their evolutionary relationships to TBDT of other bacteria. We biochemically studied the iron uptake systems of C. crescentus, identified potential iron transporters, and clarified the phylogenetic relationships among its numerous TBDT. Our findings identified the first outer membrane protein involved in iron acquisition by C. crescentus, its heme/hemoglobin transporter (HutA).

Effect of recent historical events on migration and isonymic stratification among the Rama Amerindians from Nicaragua.

The Rama Amerindians from southern Nicaragua are one of few indigenous populations inhabiting the east coast and lowlands of southern Central America. Early-eighteenth-century ethnohistorical accounts depicted the Rama as a mobile hunter-gatherer and horticulturalist group dispersed in household units along southern Nicaraguan rivers. However, during the nineteenth and twentieth centuries, Rama settlement patterns changed to aggregated communities because of increased competition for local resources resulting from nonindigenous immigration. The objective of this study was to discern the degree of relatedness between and within subdivisions of seven of these communities based on patterns of surname variation and genealogical data. We applied surname analyses (n = 592) to evaluate inter- and intrapopulation variation, consanguinity and substructure estimates, and isolation by distance and used a genealogically based marital migration matrix obtained during fieldwork in 2007 and 2009 to better understand internal migration. Our evaluation indicates a pattern of geographic distribution linking kinships in major subpopulations to nearby family-based villages. Mantel tests provide a correlation (r = 0.4; p < 0.05) between distance matrices derived from surname and geography among Rama communities. Genealogical analysis reveals a pattern of kin networks within both peripheral and central populations, consistent with previous genetic investigations, where the Amerindian mitochondrial DNA haplogroup B2 is commonly found among peripheral communities and A2 is frequent in central subpopulations. Marital migration and genealogies provide additional information regarding the influx of non-Ramas to communities near populated villages. These results indicate that the disruption of the Rama's traditional way of life has had significant consequences on their population structure consistent with population fissions and aggregations since the eighteenth century.

A reference genome for common bean and genome-wide analysis of dual domestications.

Common bean (Phaseolus vulgaris L.) is the most important grain legume for human consumption and has a role in sustainable agriculture owing to its ability to fix atmospheric nitrogen. We assembled 473 Mb of the 587-Mb genome and genetically anchored 98% of this sequence in 11 chromosome-scale pseudomolecules. We compared the genome for the common bean against the soybean genome to find changes in soybean resulting from polyploidy. Using resequencing of 60 wild individuals and 100 landraces from the genetically differentiated Mesoamerican and Andean gene pools, we confirmed 2 independent domestications from genetic pools that diverged before human colonization. Less than 10% of the 74 Mb of sequence putatively involved in domestication was shared by the two domestication events. We identified a set of genes linked with increased leaf and seed size and combined these results with quantitative trait locus data from Mesoamerican cultivars. Genes affected by domestication may be useful for genomics-enabled crop improvement.

Microevolution, migration, and the population structure of five Amerindian populations from Nicaragua and Costa Rica.

OBJECTIVE: This research examines the coevolution of languages and uniparental genetic marker (mitochondrial DNA [mtDNA] and nonrecombining Y-chromosome [NRY]) variation within five Lower Central American (Rama, Chorotega, Maléku, Zapatón-Huetar, and Abrojo-Guaymí) Amerindian groups. This pattern occurred since European contact. METHODS: We examined mtDNA sequence variation from the hypervariable region 1 (HVS-1) and NRY genetic variation using short tandem repeat (STR) loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, and DYS439) and NRY haplogroups (Q1a3a, Q1a3*, C3b, R1b1b2, E1b1, G2a2, and I) identified through single-nucleotide polymorphisms. Phylogenetic analysis included multidimensional scaling (MDS), heterozygosity versus rii , and analysis of molecular variance (AMOVA). RESULTS: Eighteen mtDNA haplotypes were characterized in 131 participants with 94.6% of these assigned to the Amerindian mtDNA subclades, A2 and B2. The Amerindian NRY haplogroup, Q1a3a, was present in all five groups and ranged from 85% (Zapatón-Huetar) to 35% (Chorotega). Four populations (Rama, Chorotega, Zapatón-Huetar, and Abrojo-Guaymí) were also characterized by the presence of NRY haplogroup R1b1b2 indicative of western European admixture. Seventy NRY STR haplotypes were identified of which 69 (97%) were population specific. MDS plots demonstrated genetic similarities between Mesoamericans and northern Chibchan Amerindian populations, absent in mtDNA analyses, which is further supported by heterozygosity versus rii results. CONCLUSIONS: We conclude that although these linguistically related populations in geographic proximity demonstrate a high degree of paternal genetic differentiation, recent demographic events have dramatically altered the paternal genetic structure of the regions Amerindian populations.

Genetic architecture of carotid artery intima-media thickness in Mexican Americans.

BACKGROUND- Intima-media thickness (IMT) of the common and internal carotid arteries is an established surrogate for atherosclerosis and predicts risk of stroke and myocardial infarction. Often IMT is measured as the average of these 2 arteries; yet, they are believed to result from separate biological mechanisms. The aim of this study was to conduct a family-based genome-wide association study (GWAS) for IMT to identify polymorphisms influencing IMT and to determine if distinct carotid artery segments are influenced by different genetic components. METHODS AND RESULTS- IMT for the common and internal carotid arteries was determined through B-mode ultrasound in 772 Mexican Americans from the San Antonio Family Heart Study. A GWAS using 931219 single-nucleotide polymorphisms was undertaken with 6 internal and common carotid artery IMT phenotypes using an additive measured genotype model. The most robust association detected was for 2 single-nucleotide polymorphisms (rs16983261, rs6113474; P=1.60e(-7)) in complete linkage disequilibrium on chromosome 20p11 for the internal carotid artery near wall, next to the gene PAX1. We also replicated previously reported GWAS regions on chromosomes 19q13 and 7q22. We found no overlapping associations between internal and common carotid artery phenotypes at P<5.0e(-6). The genetic correlation between the 2 carotid IMT arterial segments was 0.51. CONCLUSIONS- This study represents the first large-scale GWAS of carotid IMT in a non-European population and identified several novel loci. We do not detect any shared GWAS signals between common and internal carotid arterial segments, but the moderate genetic correlation implies both common and unique genetic components.

Hexa-kis-(dimethyl sulfoxide-κO)zinc(II) poly-iodide.

The title compound, [Zn{(CH3)2SO}6]I4, is a one-dimensional supra-molecular polymer along a threefold rotation axis of the space group. It is built up from discrete [Zn{(CH3)2SO}6](2+) units connected through non-classical hydrogen bonds to linear I4 (2-) polyiodide anions (C-H⋯I = 3.168 Å). The Zn(II) ion in the cation has an octa-hedral coordination geometry, with all six Zn-O bond lengths being equivalent, at 2.111 (4) Å. The linear polyiodide anion contains a neutral I2 mol-ecule weakly coordinated to two iodide ions.

Genetic structure of Tribolium castaneum (Coleoptera: Tenebrionidae) populations in mills.

The red flour beetle, Tribolium castaneum (Herbst), is primarily found associated with human structures such as wheat and rice mills. Such structures are predicted to be spatially isolated resource patches with frequent population bottlenecks that should influence their genetic structure. Genetic diversity and differentiation among nine populations of T. castaneum collected from wheat and rice mills (ranging from <1-5,700 km apart) were investigated using eight polymorphic loci (microsatellites and other insertion-deletion polymorphisms, each with 3-14 alleles). Seventy-two locus-by-population combinations were evaluated, of which 31 deviated significantly from Hardy-Weinberg equilibrium, all because of a deficiency of heterozygotes. AMOVA analysis indicated significant differences among populations, with 8.3% of the variation in allele frequency resulting from comparisons among populations, and commodity type and geographic region not significant factors. Although there were significant differences in genetic differentiation among populations (F(ST) values = 0.018-0.149), genetic distance was not significantly correlated with geographic distance. Correct assignment to the source population was successful for only 56% of individuals collected. Further analyses confirmed the occurrence of recent genetic bottlenecks in five out of nine populations. These results provide evidence that populations of T. castaneum collected from mills show spatial genetic structure, but the poor ability to assign individuals to source populations and lack of isolation by distance suggest greater levels of gene flow than predicted originally.

Large scale mitochondrial sequencing in Mexican Americans suggests a reappraisal of Native American origins.

BACKGROUND: The Asian origin of Native Americans is largely accepted. However uncertainties persist regarding the source population(s) within Asia, the divergence and arrival time(s) of the founder groups, the number of expansion events, and migration routes into the New World. mtDNA data, presented over the past two decades, have been used to suggest a single-migration model for which the Beringian land mass plays an important role. RESULTS: In our analysis of 568 mitochondrial genomes, the coalescent age estimates of shared roots between Native American and Siberian-Asian lineages, calculated using two different mutation rates, are A4 (27.5 ± 6.8 kya/22.7 ± 7.4 kya), C1 (21.4 ± 2.7 kya/16.4 ± 1.5 kya), C4 (21.0 ± 4.6 kya/20.0 ± 6.4 kya), and D4e1 (24.1 ± 9.0 kya/17.9 ± 10.0 kya). The coalescent age estimates of pan-American haplogroups calculated using the same two mutation rates (A2:19.5 ± 1.3 kya/16.1 ± 1.5 kya, B2:20.8 ± 2.0 kya/18.1 ± 2.4 kya, C1:21.4 ± 2.7 kya/16.4 ± 1.5 kya and D1:17.2 ± 2.0 kya/14.9 ± 2.2 kya) and estimates of population expansions within America (~21-16 kya), support the pre-Clovis occupation of the New World. The phylogeography of sublineages within American haplogroups A2, B2, D1 and the C1b, C1c and C1d subhaplogroups of C1 are complex and largely specific to geographical North, Central and South America. However some sub-branches (B2b, C1b, C1c, C1d and D1f) already existed in American founder haplogroups before expansion into the America. CONCLUSIONS: Our results suggest that Native American founders diverged from their Siberian-Asian progenitors sometime during the last glacial maximum (LGM) and expanded into America soon after the LGM peak (~20-16 kya). The phylogeography of haplogroup C1 suggest that this American founder haplogroup differentiated in Siberia-Asia. The situation is less clear for haplogroup B2, however haplogroups A2 and D1 may have differentiated soon after the Native American founders divergence. A moderate population bottle neck in American founder populations just before the expansion most plausibly resulted in few founder types in America. The similar estimates of the diversity indices and Bayesian skyline analysis in North America, Central America and South America suggest almost simultaneous (~ 2.0 ky from South to North America) colonization of these geographical regions with rapid population expansion differentiating into more or less regional branches across the pan-American haplogroups.