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Mercapto acetyl tri‐glycine renogram (MAG3) scan has been the gold standard assessment of pediatric ureteropelvic junction obstruction (UPJO) but requires intravenous access and radiation exposure. While Doppler ultrasound measurements of resistive indices (RI) of the arcuate arteries have been proposed as an alternative assessment of obstruction, they have not been widely adopted in the pediatric population. We hypothesized that RI of the main renal artery (RA) is more strongly correlated with MAG3 findings than arcuate RI. Pediatric patients with unilateral Society for Fetal Urology grade 3–4 hydronephrosis undergoing concomitant RUS and MAG3 were recruited. Doppler ultrasound peak systolic velocity (PSV); RI of bilateral RA at the origin, middle, and hilum; and RI of the superior, middle, and lower pole arcuate arteries were obtained. MAG3 differential renal function (DRF) and T½ were recorded. Differences in RI measurements (DRI) between the affected and normal kidney were calculated and compared with DRF and T½. 31 patients (median 4.6‐month‐old) were enrolled. Only RA RI at the origin differed between affected and normal kidneys (p< .001). DRI RA at the origin showed weak evidence for an association with MAG3 DRF < 40% (p.07). DRI was not associated with T½ > 20 minutes. There was weak evidence for an association between RA DRI at the origin and DRF but not with T½. These findings suggest that RA DRI may provide additional data in the evaluation of patients with UPJO to tailor the use of MAG3 and associated risk of radiation exposure to those patients most at risk for concomitant renal function impairment.

Background This study aims to assess the association of postoperative stroke with intraoperative hemodynamic variability and transfusion management.Methods In this case-control study, adult patients (≥ 18 years) who had a stroke within 72 hours of a surgical procedure were matched to 2 control patients according to age, sex, and procedure type. Primary risk factors assessed were intraoperative fluid administration, blood product transfusion, vasopressor use, and measures of variability in systolic and diastolic blood pressure and heart rate: maximum, minimum, range, SD, and average real variability. The variables were analyzed with conditional logistic regression, which accounted for the 1:2 matched case-control study design.Results Among 687 581 procedures, we identified 64 postoperative strokes (incidence, 9.3 [95% CI, 7.2-11.9] strokes per 100 000 procedures). These cases were matched with 128 controls. Stroke cases had higher Charlson cmorbidity index scores than did controls (P = .046). Blood pressure and heart rate variability measures were not associated with stroke. The risk of stroke was increased with red blood cell (RBC) transfusion (odds ratio [OR], 14.82; 95% CI, 3.40-64.66; P < .001), vasopressor use (OR, 3.91; 95% CI, 1.59-9.60; P = .003), and longer procedure duration (OR, 1.23/h; 95% CI, 1.01-1.51; P = .04). Multivariable analysis of procedure duration, RBC transfusion, and vasopressor use showed that only RBC transfusion was independently associated with an increased risk of stroke (OR, 10.10; 95% CI, 2.14-47.72; P = .004).Conclusions Blood pressure variability was not associated with an increased risk of postoperative stroke; however, RBC transfusion was an independent risk factor.

Metal–organic frameworks have developed into a formidable heterogeneous catalysis platform in recent years. It is well established that thermolysis of coordinated solvents from MOF nodes can render highly reactive, coordinatively unsaturated metal complexes which are stabilized via site isolation and serve as active sites in catalysis. Such approaches are limited to frameworks featuring solvated transition-metal complexes and must be stable toward the formation of “permanent” open metal sites. Herein, we exploit the hemilability of metal–carboxylate bonds to generate transient open metal sites in an In(III) MOF, pertinent to In-centered catalysis. The transient open metal sites catalyze the Strecker reaction over multiple cycles without loss of activity or crystallinity. We employ computational and spectroscopic methods to confirm the formation of open metal sites via transient dissociation of In(III)–carboxylate bonds. Furthermore, the amount of transient open metal sites within the material and thus the catalytic performance can be temperature-modulated.

Background Postoperative falls are preventable complications. The study aims were to describe the rate and circumstances surrounding postoperative falls and explore potential associations with patient and procedural characteristics with emphasis on the use of sedative medications.Methods Medical records of hospitalized patients undergoing non-lower extremity surgery under general anesthesia from January 1, 2010, through April 30, 2018 were reviewed for falls within 72 postoperative hours. Perioperative use of sedatives, sleep aids, gabapentinoids, and opioids were abstracted. Each fall case was matched with two controls on age, sex, and procedure type. Descriptive statistics and multivariable analysis accounting for the matched design were performed.Results There were 343 falls among 200 186 hospitalized surgical patients (incidence of 17.1 [95% CI: 15.4, 19.0] falls per10 000 procedures) with largest proportion of falls occurring on postoperative day 2 (n = 134, 39.1%). Most falls occurred in the general hospital wards (n = 304, 88.6%) and were unwitnessed (n = 186, 55.9%). The incidence of major injuries was 1.0 (95% CI: .1 – 3.6) per100 000 procedures. Home use of non-benzodiazepine hypnotics (odds ratio 2.68, 95% CI: 1.47, 4.88, P=.001) and blood transfusions were associated with increased fall risk. Hospital stay was longer in patients who fall (7 [4, 15] vs. 5 [3, 9] days, P < .001).Conclusions The rate of postoperative falls in our institution was low and frequently unwitnessed. The use of non-benzodiazepine hypnotics is a modifiable risk factor associated with postoperative falls. Serious complications after falls were rare.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive pediatric cancer. Amongst the wide array of driver mutations, 10% of T-ALL patients display gain-of-function mutations in the IL-7 receptor α chain (IL-7Rα, encoded by IL7R), which occur in different molecular subtypes of this disease. However, it is still unclear whether IL-7R mutational activation is sufficient to transform T-cell precursors. Also, which genes cooperate with IL7Rto drive leukemogenesis remain poorly defined. Here, we demonstrate that mutant IL7Ralone is capable of inducing T-ALL with long-latency in stable transgenic zebrafish and transformation is associated with MYCtranscriptional activation. Additionally, we find that mutant IL7Rcollaborates with Myc to induce early onset T-ALL in transgenic zebrafish, supporting a model where these pathways collaborate to drive leukemogenesis. T-ALLs co-expressing mutant IL7Rand Mycactivate STAT5 and AKT pathways, harbor reduced numbers of apoptotic cells and remake tumors in transplanted zebrafish faster than T-ALLs expressing Myc alone. Moreover, limiting-dilution cell transplantation experiments reveal that activated IL-7R signaling increases the overall frequency of leukemia propagating cells. Our work highlights a synergy between mutant IL7Rand Myc in inducing T-ALL and demonstrates that mutant IL7Renriches for leukemia propagating potential.

The molecular bases for the symbiosis of the amphibian skin microbiome with its host are poorly understood. Here, we used the odor-producer Pseudomonassp. MPFS and the treefrog Boana prasinaas a model to explore bacterial genome determinants and the resulting mechanisms facilitating symbiosis. Pseudomonassp. MPFS and its closest relatives, within a new clade of the P. fluoresensGroup, have large genomes and were isolated from fishes and plants, suggesting environmental plasticity. We annotated 16 biosynthetic gene clusters from the complete genome sequence of this strain, including those encoding the synthesis of compounds with known antifungal activity and of odorous methoxypyrazines that likely mediate sexual interactions in Boana prasina. Comparative genomics of Pseudomonasalso revealed that Pseudomonassp. MPFS and its closest relatives have acquired specific resistance mechanisms against host antimicrobial peptides (AMPs), specifically two extra copies of a multidrug efflux pump and the same two-component regulatory systems known to trigger adaptive resistance to AMPs in P. aeruginosa. Subsequent molecular modeling indicated that these regulatory systems interact with an AMP identified in Boana prasinathrough the highly acidic surfaces of the proteins comprising their sensory domains. In agreement with a symbiotic relationship and a highly selective antibacterial function, this AMP did not inhibit the growth of Pseudomonassp. MPFS but inhibited the growth of another Pseudomonasspecies and Escherichia coliin laboratory tests. This study provides deeper insights into the molecular interaction of the bacteria-amphibian symbiosis and highlights the role of specific adaptive resistance toward AMPs of the hosts.

Background Postoperative in-hospital pneumonia is a serious complication. This study aims to investigate the association between 3 preoperative stratification tools (American Society of Anesthesiologists Physical Status [ASA-PS] score, Charlson Comorbidity Index [CCI], and Rockwood Frailty Deficit Index [FI]) and risk for postoperative pneumonia.Methods We identified adult patients who developed postoperative pneumonia following noncardiothoracic surgery under general anesthesia, between January 1, 2016 and December 31, 2017. Patients with postoperative pneumonia were 1:1 matched to control subjects based on age, sex, and the exact type of operations. Medical records were reviewed to identify variables that may be associated with risk for developing postoperative pneumonia. Analyses adjusted for clinical characteristics were performed using the conditional logistic regression, taking into account 1:1 matched set case-control study design.Results We identified 211 cases of postoperative pneumonia, and all 3 tested stratification tools were associated with increased risk: ASA-PS (after all adjustments of American Society of Anesthesiologists (ASA) III, odds ratio 4.17 [95% confidence interval 1.74-10.01]; ASA > III 24.03 [6.54-88.32]), CCI (CCI values > 3, 1.29 [1.02-1.63] per unit CCI score), and frail FI score 3.25 (1.45-7.27). Because of incomplete intake documentation, the FI could not be calculated in 57 (13.5%) patients, but these “unknown frailty” patients were also at increased risk for postoperative pneumonia, 3.15 (1.29-7.72).Discussion Three commonly used stratification indices (ASA-PS score, CCI, and FI) were associated with increased risk for postoperative pneumonia. Patients unable to complete intake form to calculate the FI were also at increased risk.

To investigate the association between episodes of critical care hospitalizations and delirium with structural brain changes in older adults.

Purpose: This series of meta-analyses were aimed to elucidate the impact of hypothyroidism on low-grade systemic inflammation and oxidative stress assessed by C-reactive protein (CRP) and malondialdehyde (MDA) respectively; and to evaluate the effect of levothyroxine replacement therapy (LRT) on those outcomes. Methods: PubMed database and the key studies references were searched prior to March 3, 2020. Data on serum or plasma CRP and MDA levels in SHT (subclinical) and/or OHT (overt) hypothyroid patients and controls were extracted to compute overall standardized mean differences (SMD) by the random-effects model. Results: A total of 93 studies were entered into analyses and ten main meta-analyses were performed. OHT (SMD = 0.72 [0.39; 1.04], k= 35), SHT (SMD = 1.58 [0.78; 2.38], k= 56) and even mild SHT (TSH &lt; 10 mU/L, SMD = 2.19 [0.02; 4.37], k= 13) proved to have a detrimental effect on CRP levels. LRT showed a favorable effect on CRP levels, particularly in OHT (SMD = −0.30 [−0.57; −0.02], k= 17). Increased levels of MDA were also found, especially in OHT (SMD = 2.49 [0.66; 4.31], k= 13). LRT may also improve MDA levels; however future studies would further validate the advantageous effect of LRT in hypothyroidism. Heterogeneity primarily originated from different study designs and geographic locations. Conclusion: Overall, these meta-analyses reveal that screening for hs-CRP and MDA in hypothyroid patients as simple biomarkers of low-grade systemic inflammation and oxidative stress may become a useful tool to identify those at increased risk who may benefit most from early interventions.

Anthropogenic climate warming affects many biological systems, ranging in scale from microbiomes to biomes. In many animals, warming-related fitness depression appears more closely linked to changes in ecological community interactions than to direct thermal stress. This biotic community framework is commonly applied to warming studies at the scale of ecosystems but is rarely applied at the scale of microbiomes. Here, we used replicated bromeliad microecosystems to show warming effects on tadpole gut microbiome dysbiosis mediated through biotic community interactions. Warming shifted environmental bacteria and arthropod community composition, with linkages to changes in microbial recruitment that promoted dysbiosis and stunted tadpole growth. Tadpole growth was more strongly associated with cascading effects of warming on gut dysbiosis than with direct warming effects or indirect effects on food resources. These results suggest that assessing warming effects on animal health requires an ecological community perspective on microbiome structure and function.

A new material, MOF-type [Ir]@NU-1000, was accessed from the incorporation of the iridium organometallic fragment [Ir{κ3(P,Si,Si)PhP(o-C6H4CH2SiiPr2)2}] into NU-1000. The new material incorporates less than 1 wt % of Ir(III) (molar ratio Ir to NU-1000, 1:11), but the heat of adsorption for SO2is significantly enhanced with respect to that of NU-1000. Being a highly promising adsorbent for SO2capture, [Ir]@NU-1000 combines exceptional SO2uptake at room temperature and outstanding cyclability. Additionally, it is stable and can be regenerated after SO2desorption at low temperature.

A virtual screening conducted with nearly 4 000 000 compounds from lead-like and fragment-like subsets enabled the identification of a small-molecule inhibitor (1) of the Trypanosoma cruzicruzain enzyme, a validated drug target for Chagas disease. Subsequent comprehensive structure-based drug design and structure–activity relationship studies led to the discovery of carbamoyl imidazoles as potent, reversible, and competitive cruzain inhibitors. The most potent carbamoyl imidazole inhibitor (45) exhibited high affinity with a Kivalue of 20 nM, presenting both in vitroand in vivoactivity against T. cruzi. Furthermore, the most promising compounds reduced parasite burden in vivoand showed no toxicity at a dose of 100 mg/kg. These carbamoyl imidazoles are structurally attractive, nonpeptidic, and easy to prepare and synthetically modify. Finally, these results further advance our understanding of the noncovalent mode of inhibition of this pharmaceutically relevant enzyme, building strong foundations for drug discovery efforts.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with a dismal prognosis in patients with resistant or relapsed disease. Although NOTCH is a known driver in T-ALL, its clinical inhibition has significant limitations. Our previous studies suggested that NRARP, a negative regulator of Notch signaling, could have a suppressive role in T-ALL. Here, we report that NRARP levels are significantly increased in primary T-ALL cells suggesting that NRARP is not sufficient to block NOTCH oncogenic signals. Interestingly, although NRARP overexpression blocks NOTCH1 signaling and delays the proliferation of T-ALL cells that display high levels of Notch1 signaling, it promotes the expansion of T-ALL cells with lower levels of Notch1 activity. We found that NRARP interacts with lymphoid enhancer-binding factor 1 (LEF1) and potentiates Wnt signaling in T-ALL cells with low levels of Notch. Together these results indicate that NRARP plays a dual role in T-ALL pathogenesis, regulating both Notch and Wnt pathways, with opposite functional effects depending on Notch activity. Consistent with this hypothesis, mice transplanted with T-cells co-expressing NOTCH1 and NRARP develop leukemia later than mice transplanted with T-NOTCH1 cells. Importantly, mice transplanted with T-cells overexpressing NRARP alone developed leukemia with similar kinetics to those transplanted with T-NOTCH1 cells. Our findings uncover a role for NRARP in T-ALL pathogenesis and indicate that Notch inhibition may be detrimental for patients with low levels of Notch signaling, which would likely benefit from the use of Wnt signaling inhibitors. Importantly, our findings may extend to other cancers where Notch and Wnt play a role.

Genetic factors have been implicated in suicidal behavior. It has been suggested that one of the roles of genetic factors in suicide could be represented by the effect of genetic variants on gene expression regulation. Alteration in the expression of genes participating in multiple biological systems in the suicidal brain has been demonstrated, so it is imperative to identify genetic variants that could influence gene expression or its regulatory mechanisms. In this study, we integrated DNA methylation, gene expression, and genotype data from the prefrontal cortex of suicides to identify genetic variants that could be factors in the regulation of gene expression, generally called quantitative trait locus (xQTLs). We identify 6,224 methylation quantitative trait loci and 2,239 expression quantitative trait loci (eQTLs) in the prefrontal cortex of suicide completers. The xQTLs identified influence the expression of genes involved in neurodevelopment and cell organization. Two of the eQTLs identified (rs8065311 and rs1019238) were previously associated with cannabis dependence, highlighting a candidate genetic variant for the increased suicide risk in subjects with substance use disorders. Our findings suggest that genetic variants may regulate gene expression in the prefrontal cortex of suicides through the modulation of promoter and enhancer activity, and to a lesser extent, binding transcription factors.

Insects in the order Hymenoptera are considered useful indicators of environmental changes, and yellow pan-traps constitute one of the most used sampling methods to collect them. Here, we analyze the influence of microsite features on the flying Hymenoptera communities obtained using yellow pan-traps, through a short time of exposure in three microsites of fragmented forest: interior (I), north (NB) and south facing (SB) borders. We compared values of richness and abundance of total Hymenoptera, as well as parasitoids, predators and pollinators among microsites using rarefaction and extrapolation curves and Generalized Linear Mixed Models. Number of individuals obtained in NB were two-fold and 74% greater than the ones obtained in SB and in I respectively, whereas estimated total species richness was higher in the forest interior, followed by SB and ultimately by NB. Parasitoids and predators were more frequently trapped in NB. Even when data were obtained through a short period of sampling in five sampling sites, our results emphasize the need to consider the influence of the location (border vs interior) and the geographic orientation of edges in which pan-traps are placed in order to correctly assess the abundance of flying Hymenoptera in fragmented forest landscapes.

-TNF via NFκB pathway is induced in response to anti-CD3 immunotherapy in T-ALL PDXs-TNF neutralization and the SMAC mimetic Birinapant synergize with anti-CD3-induced cell death and anti-leukemic properties

•SARS-CoV-2 Spike protein (Spk) induces intestinal chloride secretion in mice;•Spk causes lysozymes depletion by Paneth cells degranulation;•Spk diminishes mucus blanket associated with mucin 2 reduction;•Mucosal intestinal barrier is impaired by Spk inoculation on the gut;•Spk triggers local inflammation and dysmotility on the gut.

Presenting a succinct literature review, 'MRI of Placenta Accreta Spectrum - A Comprehensive Literature Review of the Most Recent Advancements' delves into the latest MRI developments dedicated to diagnosing Placenta Accreta Spectrum (PAS). PAS, characterized by abnormal placental adherence to the uterine wall, is of paramount concern due to its association with maternal morbidity and mortality, particularly in high-risk pregnancies featuring placenta previa and prior cesarean sections.

Metal–organic frameworks (MOFs), a sort of crystalline porous coordination polymers composed of metal ions and organic linkers, have been intensively studied for their ability to take up nonpolar gas-phase molecules such as ethane and ethylene. In this context, interpenetrated MOFs, where multiple framework nets are entwined, have been considered promising materials for capturing nonpolar molecules due to their relatively higher stability and smaller micropores. This study explores a solvent-assisted reversible strategy to interpenetrate and deinterpenetrate a Cu(II)-based MOF, namely, MOF-143 (noninterpenetrated form) and MOF-14 (doubly interpenetrated forms). Interpenetration was achieved using protic solvents with small molecular sizes such as water, methanol, and ethanol, while deinterpenetration was accomplished with a Lewis-basic solvent, pyridine. Additionally, this study investigates the adsorptive separation of ethane and ethylene, which is a significant application in the chemical industry. The results showed that interpenetrated MOF-14 exhibited higher ethane and ethylene uptakes compared to the noninterpenetrated MOF-143 due to narrower micropores. Furthermore, we demonstrate that pristine MOF-14 displayed higher ethane selectivity than transformed MOF-14 from MOF-143 by identifying the “fraction of micropore volume” as a key factor influencing ethane uptake. These findings highlight the potential of controlled transformations between interpenetrated and noninterpenetrated MOFs, anticipating that larger MOF crystals with narrower micropores and higher crystallinity will be more suitable for selective gas capture and separation applications.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological cancer for which treatment options often result in incomplete therapeutic efficacy and long-term side-effects. Interleukin 7 (IL-7) and its receptor IL-7Rα promote T-ALL development and mutational activation of IL-7Rα associates with very high risk in relapsed disease. Using combinatorial phage-display libraries and antibody reformatting, we generated a fully human IgG1 monoclonal antibody (named B12) against both wild-type and mutant human IL-7Rα, predicted to form a stable complex with IL-7Rα at a different site from IL-7. B12 impairs IL-7/IL-7R-mediated signaling, sensitizes T-ALL cells to treatment with dexamethasone and can induce cell death per se. The antibody also promotes antibody-dependent natural killer-mediated leukemia cytotoxicity in vitro and delays T-cell leukemia development in vivo, reducing tumor burden and promoting mouse survival. B12 is rapidly internalized and traffics to the lysosome, rendering it an attractive vehicle for targeted intracellular delivery of cytotoxic cargo. Consequently, we engineered a B12–MMAE antibody–drug conjugate and provide proof-of-concept evidence that it has increased leukemia cell killing abilities as compared with the naked antibody. Our studies serve as a stepping stone for the development of novel targeted therapies in T-ALL and other diseases where IL-7Rα has a pathological role.

The New World screwworm fly Cochliomyia hominivorax(Coquerel, 1858) (Diptera: Calliphoridae) is an important livestock pest endemic to the Americas that has been eradicated from North and continental Central America with a control program based on the Sterile Insect Technique (SIT). The establishment of target management units is a strategic step in the implementation of new control programs, which can be achieved using genetic studies of natural populations. Previous studies of New World screwworm fly populations were conducted on the continental scale and identified four main groups: two in South America and two in the Caribbean. However, studies within these groups are needed to determine which smaller geographic areas can be treated as management units. Here, we analyze the genetic variability distribution and the population demographic signals of the New World screwworm fly in a 6,000 km2area located along the border of Brazil and Uruguay. This area was the subject of the first control pilot program conducted in South America. We studied eight microsatellite loci and sequences from two mitochondrial DNA regions in individuals sampled at 20–25 livestock breeding farms. We observed no population structure and found high genetic variability on the geographical scale sampled for both molecular markers. Our microsatellite data suggest that these populations are not in equilibrium, and demographic analyses based on mitochondrial data indicate population expansion. These results suggest that this geographic scale is not adequate for future New World screwworm fly management in South America.

The biological activity of tellurium compounds is closely related to the tellurium oxidation state or some of their structural features. Hypervalent dihalogenated organotelluranes 1-[butyl(dichloro)-λ4-tellanyl]-2-(methoxymethyl)benzene (1a) and 1-[butyl(dibromide)-λ4-tellanyl]-2-(methoxymethyl)benzene (1b) have been described as inhibitors of proteases (cysteine and threonine) and tyrosine phosphatases. However, poor attention has been given to their physicochemical properties. Here, a detailed investigation of the stability in water of these organotelluranes is reported using 125Te NMR analysis. Dihalogenated organotelluranes 1aand 1bwere both stable in DMSO-d6(from 25 to 75 °C), demonstrating their thermal stability. However, the addition of a phosphate buffer solution (pH 2–8) to 1aor 1bresulted in an immediate conversion to a new Te species, assumed to be the corresponding telluroxide. Similar behavior was observed in pure water, demonstrating the low chemical stability of these dihalogenated species in the presence of water. These results allow concluding that previous biological activity reported for dihalogenated organotelluranes 1aand 1bcould be attributed to the corresponding derivatives from the reaction with water. In the same way as for AS-101, we demonstrated that organotelluranes 1aand 1bare not stable in aqueous solution. It suggests a proactive role of these organotelluranes in previously reported biological activity.

Neonatal intestinal obstruction is caused by an anatomical abnormality that produces bowel movement failure. Intestinal obstruction presents with three classic clinical signs: vomiting, abdominal distention, and failure to pass meconium. Intestinal obstruction is one of the most common causes for admitting a pediatric patient to the pediatric surgery unit in his or her first weeks of postnatal life. Congenital obstruction of the digestive tract in neonates is a common problem, with the most frequent cause being anorectal malformations (41%), followed by esophageal obstruction (24%), and duodenal obstruction (20%). Neonatal intestinal obstruction is caused by an anatomical abnormality that produces bowel movement failure. Intestinal obstruction presents with three classic clinical signs: vomiting, abdominal distention, and failure to pass meconium. Intestinal obstruction is one of the most common causes for admitting a pediatric patient to the pediatric surgery unit in his or her first weeks of postnatal life. Congenital obstruction of the digestive tract in neonates is a common problem, with the most frequent cause being anorectal malformations (41%), followed by esophageal obstruction (24%), and duodenal obstruction (20%). [[Pediatr Ann.2018;47(5):e220–e225.]

The current management paradigm for children with single ventricle heart disease involves a series of palliative surgeries, culminating in the Fontan operation. This physiology results in a high central venous pressure, and in the setting of single ventricle heart disease, results in hepatic injury and fibrosis over time. Fontan‐associated liver disease (FALD) is universally present in this cohort, and the current gold standard for diagnosis remains biopsy. Noninvasive assessments of liver fibrosis, such as ultrasound with elastography or acoustic radiation force impulse (ARFI), has been utilized in this cohort. The effect of poor cardiovascular efficiency, as measured by cardiopulmonary exercise test (CPET), on assessments of liver fibrosis remains poorly understood. Retrospective, cross‐sectional study. Subjects were evaluated in a multidisciplinary clinic setting for patients who have undergone Fontan operation. CPETs, liver ultrasound with elastography (ARFI), and standard laboratory tests were performed as part of routine clinical care pathway. Statistical analysis included linear correlation. There was a poor correlation between mean ARFI velocity and peak oxygen consumption (VO2max) in this cohort (r =.20, P =NS). Similarly, there was poor correlation between ARFI and biomarkers of liver injury, time since Fontan operation and Fontan pressure. ARFI had poor correlation with functional capacity after Fontan, as measured by VO2maxobtained during CPET. While a single measurement of liver elastography was not associated with cardiopulmonary efficiency, longitudinal data may reveal an association.

Congenital heart disease (CHD) is the most common congenital disorder among live births. When associated with extracardiac abnormalities, it is characterized as a syndromic heart disease (syndromic CHD) and corresponds to 25% of all liveborn infants with a heart defect. The etiology in about 65% of the cases still remains unknown, and in about 35% of the patients, it is associated with genetic factors. In the present study, MLPA and SNP-array techniques were used to investigate a group of 47 patients with syndromic CHD. In total, 16 defects (34%) were identified, of which 12 (25.5%) were classified as pathogenic or probably pathogenic. The most frequent abnormalities were 22q11.2 deletion (22q11.2 deletion syndrome) and 7q11.23 deletion (Williams-Beuren syndrome). We also show that rarer malformations may be associated with syndromic CHD, such as 14q32.33 deletion as well as 17q25.3, 15q11.2 (BP1-BP2), 22q13.31, and 12p13.31 (SLC2A3) duplications. The present study demonstrates that CNVs are important causal factors and should be studied in patients with syndromic CHD. Furthermore, the use of MLPA as a first screening test was appropriate, as this less expensive technology detected 11 of the 12 pathogenic abnormalities (91.6%).

Chromosomal changes are frequently observed in patients with syndromic seizures. Understanding the genetic etiology of this pathology is crucial for the guidance and genetic counseling of families as well as for the establishment of appropriate treatment. A combination of MLPA kits was used to identify pathogenic CNVs in a group of 70 syndromic patients with seizures. Initially, a screening was performed for subtelomeric changes (MLPA P036 and P070 kits) and for the regions most frequently related to microdeletion/microduplication syndromes (MLPA P064). Subsequently, the MLPA P343 was used to identify alterations in the 15q11q13, 16p11.2, and 22q13 regions. Screening with MLPA P343 allowed a 10-15.7% increase in the detection rate of CNVs reinforcing the importance of investigating changes in 15q11q13 and 16p11.2 in syndromic patients with seizures. We also demonstrated that the MLPA technique is an alternative with a great diagnostic potential, and we proposed its use as part of the initial assessment of syndromic patients with seizures.

Histones are well-conserved proteins that form the basic structure of chromatin in eukaryotes and undergo several post-translational modifications, which are important for the control of transcription, replication, DNA damage repair, and chromosome condensation. In early branched organisms, histones are less conserved and appear to contain alternative sites for modifications, which could reveal evolutionary unique functions of histone modifications in gene expression and other chromatin-based processes. Here, by using high-resolution mass spectrometry, we identified and quantified histone post-translational modifications in two life cycle stages of Trypanosoma cruzi, the protozoan parasite that causes Chagas disease. We detected 44 new modifications, namely: 18 acetylations, seven monomethylations, seven dimethylations, seven trimethylations, and four phosphorylations. We found that replicative (epimastigote stage) contains more histone modifications than nonreplicative and infective parasites (trypomastigote stage). Acetylations of lysines at the C-terminus of histone H2A and methylations of lysine 23 of histone H3 were found to be enriched in trypomastigotes. In contrast, phosphorylation in serine 23 of H2B and methylations of lysine 76 of histone H3 predominates in proliferative states. The presence of one or two methylations in the lysine 76 was found in cells undergoing mitosis and cytokinesis, typical of proliferating parasites. Our findings provide new insights into the role of histone modifications related to the control of gene expression and cell-cycle regulation in an early divergent organism.

Introduction:This case identifies vagal tone as a paradoxical cause of coronary artery spasm, coinciding with complete heart block. It will additionally identify proper management in these cases.Clinical Presentation:A 53 year old male with a medical history of HIV not of ART, acute, infectious COVID-19 and late, latent syphilis admitted for malaise, found to have DLBCL. Following a routine blood draw the patient experienced acute chest and abdominal pain. Minutes later, while having a bowel movement he experienced syncope with heart rates in the 30s. EKG showed ST elevations in leads II, III, and aVF. Troponin-T was elevated to 0.15. Echocardiogram showed inferior wall hypokinesis. Coronary angiography showed non-obstructive right coronary disease. Cardiac MRI demonstrated no evidence of infiltrative disease or myocarditis. The patient experienced a similar episode the following morning, during blood draw, EKG and telemetry demonstrated complete heart block with ST elevations (image). This suggested vagal mediated AV block with coronary artery spasm (CAS). He was started on the anticholinergic hyoscyamine and amlodipine for vasodilation. Following initiation of therapy, the patient had no further episodes of chest pain or bradycardia.Discussion:While acetylcholine causes vasodilation via endothelial NO, interestingly, it can also lead to CAS. In the setting of vascular smooth muscle cell (VSMC) hyper-reactivity or high vagal tone, VSMC muscarinic receptors are activated leading to vasoconstriction. Vagal tone can cause both CAS with resulting STEMI as well as AV blockade resulting in high degree heart block (image). When ischemic symptoms are accompanied by AV block in the setting of high vagal tone, consider vagal mediated CAS. Calcium channel blockers such as amlodipine are used to manage CAS. When the suspected mechanism is vagal tone, management includes avoidance of precipitating factors and or anticholinergic premedication.

BackgroundThe Cardiovascular Research Initiative (CVRI) was founded in 2021 by leaders and members of the American College of Cardiology (ACC) Medical Student Member Community (MSMC) to bring together students passionate about conducting cardiovascular research. The group comprises 62 students who worked on 7 review articles since December 2021 under the guidance of physician mentors. The CVRI also aims to develop members’ research knowledge and skills and thus held a webinar on ‘Key Steps in Conducting Systematic Reviews’ in February 2022.MethodsTwo surveys were created and distributed to members of the ACC MSMC. The surveys were used to assess the overall impact of the Research Initiative and Systematic Review Webinar on the career development of medical students and evaluate the diversity of participants and inclusiveness of the projects.ResultsFrom the Research Initiative author survey (n = 12), 92% of respondents identified as being from underrepresented backgrounds, had prior research experience and believe that research is a valuable part of their professional development. All respondents agreed that after participating in these research projects, they are likely to pursue research later in their careers, and 92% strongly believe that participating in the Research Initiative is a valuable experience for their research career development.The Systematic Review Webinar feedback survey (n = 12) was completed by 30% of attendees, most of whom were in their last 2 years of medical school from 8 different countries. A total of 84% of respondents felt that the webinar improved their knowledge of performing a systematic review and 50% felt prepared to conduct a systematic review after attending. Additionally, 84% felt that the virtual nature of the webinar enhanced their research knowledge and would attend and recommend future webinars on research methods and related topics.ConclusionsThe CVRI provides students from various countries and underrepresented backgrounds with opportunities and knowledge to succeed in research through manuscript writing experience and educational webinars. With its growing number of participants, the ACC MSMC continues to cultivate cardiovascular research career development among medical students.

Background:Acupuncture has shown the capability of modulating the immuno‐inflammatory response of the host. This study aims to evaluate the effects of electroacupuncture (EA) on ligature‐induced periodontitis in rats. Methods:Thirty‐two animals were divided into four groups: 1) control; 2) experimental periodontitis (EP); 3) sham‐treated (EP/EA‐sham); and 4) treated with EA (EP/EA). For the EP groups, a ligature was placed around the right mandibular first molars at day 1. Sessions of EA or EA‐sham were assigned every other day. For EA treatment, large intestine meridian points LI4 and LI11 and stomach meridian points ST36 and ST44 were used. EA‐sham was performed in off‐meridian points. Animals were euthanized at day 11. Histomorphometric and microtomographic analyses were performed. Immunolabeling patterns for the receptor activator of nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), and tartrate‐resistant acid phosphatase (TRAP) were assessed. Expressions of interleukin (IL)‐1β, matrix metalloproteinase (MMP)‐8, IL‐6, and cyclooxygenase (COX)‐2 messenger RNAs (mRNAs) were evaluated by quantitative reverse transcription‐polymerase chain reaction. Data were analyzed statistically (P<0.05, analysis of variance). Results:Histomorphometric and microtomographic analyses demonstrated that group EP/EA presented reduced alveolar bone loss when compared to group EP (P<0.05). Reduced RANKL immunolabeling and fewer TRAP‐positive multinucleated cells were observed in the EA‐treated group in relation to group EP. No differences were observed in OPG expression among groups. EA treatment decreased the genic expression of IL‐1β and MMP‐8 (P<0.05), increased the mRNA expression of IL‐6 (P<0.05), and did not modify the genic expression of COX‐2 in animals with EP (P>0.05). Conclusion:It can be concluded that EA reduced periodontal tissue breakdown and the expression of some proinflammatory mediators and a proresorptive factor in EP in rats.

ABSTRACT:This articles provides a close reading of colonial records from the mining region of Minas Gerais, in Brazil, to reveal ways in which women of African origin and descent helped to construct that region’s socio-economic order. It investigates the role slave and free black women played in supporting local economic exchanges, small manufacturing, gold mining, and food production. In this manner, this study rescues these women’s history from its marginal standing in the current narrative of Minas Gerais’s economic trajectory. It demonstrates, moreover, that African and African-descending women were part of the process of economic change that, by the turn of the nineteenth century, transformed the mining region into an important area of food production still supported by the practice of slavery.

The standard therapy for obstructive sleep apnea syndrome (OSAS) is continuous positive airway pressure (CPAP), but its correct and frequent use is essential to control the disease.

Background:Simvastatin is a cholesterol‐lowering drug whose pleiotropic effects may have a therapeutic impact on bone. This study evaluates the effect of simvastatin on rats subjected to experimental periodontal disease. Methods:Periodontitis was induced by ligature placement around the maxillary left second molar of rats for 11 days. Groups of six animals received oral saline or simvastatin (3, 10, and 30 mg/kg/day) until sacrifice on day 11. Alveolar bone loss was determined by macroscopic and histologic examination. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total alkaline phosphatase (TAP) were evaluated. Gingival myeloperoxidase activity and gingival levels of interleukin‐1β (IL‐1β), tumor necrosis factor‐α, IL‐10, reduced glutathione, malonaldehyde, and nitrate/nitrite were analyzed to investigate oxidative stress and inflammation. Expression of inducible nitric oxide synthase (iNOS), matrix metalloproteinases 1 and 8 (MMP‐1 and ‐8), bone morphogenetic protein‐2 (BMP‐2), receptor activator of nuclear factor κB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) were also investigated by immunohistochemistry to assess bone turnover and metabolism. Immunofluorescence microscopy was used to confirm the expression of RANKL in rats’ maxillae. Results:Treatment with simvastatin improved alveolar bone loss within all of the parameters studied, thus demonstrating anti‐inflammatory and antioxidant activity. Simvastatin reduced expression of iNOS, MMP‐1 and ‐8, RANK, and RANKL and increased BMP‐2 and OPG levels in the periodontal tissue. Simvastatin (30 mg/kg) increased TAP activity on day 11 compared with the saline group. No differences were found in the levels of AST and ALT in any of the groups studied. Conclusion:The present data suggest that simvastatin prevents inflammatory bone resorption in experimental periodontitis, which may be mediated by its anti‐inflammatory and antioxidant properties.

Obstructive sleep apnea (OSA) is associated with metabolic syndrome (MS), but it is unclear whether OSA treatment with continuous positive airway pressure (CPAP) can revert MS.

A novel serine hydroxymethyl transferase from Streptococcus thermophilus(SHMT) and a L‐threonine aldolase from Escherichia coli(LTA) were used as stereocomplementary biocatalysts for the aldol addition of glycine to N‐Cbz amino aldehydes and benzyloxyacetaldehyde (Cbz=benzyloxycarbonyl). Both threonine aldolases were classified as low‐specific L‐allo‐threonine aldolases, and by manipulating reaction parameters, such as temperature, glycine concentration, and reaction media, SHMT yielded exclusively L‐erythrodiastereomers in 34–60 % conversion, whereas LTA gave L‐threodiastereomers in 30:70 to 16:84 diastereomeric ratios and with 40–68 % conversion to product. SHMT is among the most stereoselective L‐threonine aldolases described. This is due, among other things, to its activity–temperature dependence: at 4 °C SHMT has high synthetic activity but negligible retroaldol activity on L‐threonine. Thus, the kinetic L‐erythroisomer was largely favored and the reactions were virtually irreversible, highly stereoselective, and in turn, gave excellent conversion. It was also found that treatment of the prepared N‐Cbz‐γ‐amino‐β‐hydroxy‐α‐amino acid derivatives with potassium hydroxide (1m) resulted in the spontaneous formation of 2‐oxazolidinone derivatives of the β‐hydroxyl and γ‐amino groups in quantitative yield. This reaction might be useful for further chemical manipulations of the products.

ABSTRACTIn spite of active measles virus (MV) vaccination strategies, reemergence continues to occur, impairing global eradication programs. The immune status against measles was evaluated in 350 vaccinated healthy Argentine children and teenagers who received a single dose of the MV Schwarz strain Lirugen vaccine (Aventis Pasteur). Sera were assessed for immunoglobulin G (IgG) antibodies by a commercial enzyme immunoassay (EIA) (Enzygnost; Behring), an in-house EIA, and neutralization EIA. Results obtained with these methods showed a marked decline in IgG level with increasing age. At 1 to 4 years of age, 84% of children had IgG antibodies above 200 mIU/ml, conventionally accepted as protective levels, whereas only 32% of older children and teenagers had antibody levels exceeding 200 mIU/ml. Moreover, the MV IgG content in the teenage group was significantly lower than the IgG antibody level of the group of younger children (P< 0.0001). In contrast, screening for IgG antibody levels to inactivated tetanus vaccine showed that, on average, 80% of this population was fully protected and that this high level of protection remained through the teenage years. This study suggests that within this population a considerable proportion of individuals had low measles antibody levels that may be insufficient to protect against reinfections or clinical disease.