bluuebunny/crossref_metadata_2025 huggingface dataset:
CT‐scan of a naturalized turtle (LB6)
Authors: LE FLOCH‐PRIGENT Patrice , Verdeille Stéphane , Gillot Jean‐Bernard
Published: June 2021

One naturalized turtle belonged from 50 years to the scientific library Gillot‐Brieux (Paris 6ème). It was examined by one high resolution CT‐scan (CIMOP‐Bizet, Paris). Several reconstructions were performed. Only the visceral cavity had been emptied; the neck, head and legs had been preserved in their whole. The dorsal shell did not belonged to the naturalized specimen as it was larger than the true one, underneath and laid sligthly desaxed on the highest part of the true specimen which was only preserved. This strange set was discovered just before the CT‐scan with the cut of two iron wires which fixed the apparent dorsal shell. The CT‐scan afforded a lot of morphological data on the remnant natural parts of this chelonian.
Cyclic nucleotides down regulate PAF receptor mediated effects in newborn ovine pulmonary arterial smooth muscle: significance in oxygen therapy of persistent pulmonary hypertension of the newborn (LB605)
Authors: Hanouni Mona , Cruz Belen , Opene Michael , Narvaez Vincent , Ibe Basil
Published: June 2021

Platelet activating factor (PAF) is implicated in the pathogenesis of persistent pulmonary hypertension of the newborn (PPHN). Baseline PAFr activity is higher in fetal ovine pulmonary artery smooth muscle cells (PASMC) and is augmented by hypoxia. In fetal PASMC we have shown evidence of crosstalk between PAFr‐mediated cell signaling and activity of cyclic nucleotides (Cnucs) via respective receptors PKG and PKA. Since these mechanisms are not well described in the newborn counterpart, we studied effects of Cnucs on PAFr protein expression in newborn PASMC. Because long term effects of oxygen therapy on newborn lung are not well understood, we included various oxygen tension study conditions. We hypothesize that PPHN results from failure of newborn lamb pulmonary system to down regulate PAFr activity or to up regulate vasodilatory Cnuc activity.

PASMC harvested from ovine newborns 6‐12d old were incubated for 24h with culture media or media containing 10μM cGMP or cAMP analogs or 0.1μM of PAF in normoxia (pO2~100torr), hypoxia (pO2 <40 torr) and hyperoxia (5% CO2, O2). Prostacyclin and TxA2 release were measured and compared to release by fetal PASMC. Proliferation studies were performed under the three conditions and PAFr, PKA and PKG expression were measured.

Newborn PA baseline prostacyclin level was 9‐fold greater than in fetal PA, whereas baseline production of TxA2 by newborn PA was 7‐fold less. Overall, 24h hyperoxia attenuated cell proliferation across all treatments. Cnuc treatment attenuated PAF stimulation of proliferation and decreased PAFr expression.

Elevated prostacyclin production over TxA2 suggests greater cyclooxygenase activity in newborn PA postnatally. Down regulation of PAFr effects by Cnucs indicates that normal newborn PA physiology favors vasodilatory pathways to minimize PAF‐induced hypertrophy or hyperplasia. Thus failure of newborn lung to anchor down regulation of vasoconstrictors with up regulation of vasodilators leads to pathogenesis of PPHN.
Cocaine self‐administration‐induced sensitization of the dopamine system (LB621)
Authors: Calipari Erin , Jones Sara
Published: June 2021

The ability of cocaine to bind to, and inhibit the dopamine transporter (DAT) mediates the reinforcing effects of the compound and is essential for the maintenance of self‐administration behaviors. As such, it is important to determine the changes in cocaine potency following cocaine self‐administration as they have important implications for 1.) how the DAT changes in response to repeated psychostimulant administration as well as 2.) changes in the reinforcing potential for drugs such as cocaine. Although sensitization paradigms, which result in sensitization of cocaine‐induced locomotor behavior and dopamine (DA) overflow following repeated cocaine injections, are often used as a model to study drug addiction, similar effects have been difficult to demonstrate following cocaine self‐administration. We have recently shown that intermittent access (IntA) conditions can result in enhanced cocaine potency at the DAT in the nucleus accumbens immediately following self‐administration. However, traditional sensitization paradigms often show enhanced effects following withdrawal/abstinence periods. Here we aimed to determine a time‐course of IntA‐induced DA sensitization and how a seven‐day abstinence period influences these effects. We show that while three days of IntA is not sufficient to alter evoked DA release, a seven‐day abstinence period following IntA results in augmented release. Additionally, cocaine potency is enhanced following as little as 3‐day IntA and further augmented following an abstinence period. Further, IntA plus abstinence enhanced cocaine‐induced DA release as compared to all other groups, demonstrating that following abstinence, cocaine’s ability to increase DA release and inhibit uptake at the DAT, two separate mechanisms for increasing DA levels, is augmented. Thus, the enhanced cocaine potency and cocaine‐induced release following abstinence could enhance the reinforcing efficacy and facilitate drug‐seeking for cocaine following periods of abstinence/withdrawal.

Grant Funding Source: Supported by NIH grants from NIDA [R01 DA024095, R01 DA03016, R01 DA14030, P50DA006634 (SRJ), T32 DA007246 and F31 DA031533 (ESC)]
Design and biological evaluation of multitarget compounds as potential treatment for Alzheimer disease (LB623)
Authors: Hernandez Maricarmen , Correa Jose , Martinez Federico , Benítez Claudia , Mera Elvia , Rosales Martha
Published: June 2021

Despite of the great efforts to develop of new therapies for Alzheimer´s disease (AD) treatment, acetylcholinesterase (AChE) inhibitors are still used, being only as palliative therapeutic since the pathogenesis of AD include other factors such as amyloid beta (Aβ), free radicals, etc. For this reason, we have designed compounds that have antioxidant activity, that inhibit AChE but also beta‐secretase (BACE1) and inhibit Aβ oligomerization. These designed compounds were submitted to explore their physicochemical parameters and were submit to docking studies to evaluate their affinity on protein targets in order to select the best ligand. Results of these studies suggest that two compounds M‐1 and M‐4 were the best. These compounds were synthesized and chemically characterized. In addition, the compounds M‐1 and M‐4 were evaluated in vitro to validate the theoretical data identifying that both compounds have antioxidant activity and inhibit AChE (Ki 0.12‐0.17 μM), inhibit BACE1 (IC50 15.4 nM), also inhibits the Aβ1‐42 oligomerization. For these reasons, compound M‐1 and M‐4 represents a promising compounds to be evaluated in transgenic models of AD.
Ovariectomy regulates the production of prostanoids and the MAPK pathway in rat mesenteric arteries (LB675)
Authors: Ferrer Mercedes , Andres Monica , Crabtree Matthew , del Campo Lara , del Campo Marta , Villalobo Antonio
Published: June 2021

Sex hormones regulate vascular function through nitric oxide (NO), thromboxane A2 (TXA2), and prostaglandin E2 (PGE2) among other factors. Since NO, TXA2 and PGE2 are known to regulate the epidermal growth factor receptor (EGFR) and downstream signaling pathways, the purpose of this study was to investigate whether the loss of ovarian function alters the production of these effectors regulating the activity of the mitogen‐activated protein kinase/extracellular‐regulated kinases 1 and 2 (MAPK‐ERK1/2), an EGFR downstream pathway. For this purpose, mesenteric arteries from control and ovariectomized Sprague‐Dawley rats (6‐months old) were used to analyze: i) the release of NO, TXA2 and PGE2; ii) the vascular reactivity to acetylcholine (Ach), the NO donor sodium nitroprusside, the TXA2‐mimetic compound U‐46619, and exogenous PGE2; and iii) the activation status of MAPK(ERK1/2). Our results show that ovariectomy: i) does not change NO release while decreases its vasodilator action; ii) increases the release and vasoconstrictor action of TXA2 and PGE2; and iii) increases the basal activity of the MAPK(ERK1/2) pathway. We conclude that activation of the EGFR/MAPK axis by these effectors could contribute to increase the proliferation rate of vascular smooth muscle cells, leading to increase peripheral resistance and hypertension.

Grant Funding Source: Supported by the Fondo de Investigaciones Sanitarias (PI0011406) to MF.
Sodium Nitrite Supplementation Alters the Human Metabolome in Healthy Middle‐Aged and Older Adults (LB703)
Authors: Johnson Lawrence , de Picciotto Natalie , Cruickshank‐Quinn Charmion , Reisdorph Nichole , Giordano Tony , DeVan Allison , Seals Douglas , Sindler Amy
Published: June 2021

Reduced nitric oxide (NO) bioavailability contributes to physiological dysfunction with aging. Oral sodium nitrite supplementation (SN) increases circulating nitrite, a precursor of NO, and improves some physiological functions in middle‐aged and older (MA/O) adults. To gain insight into the underlying molecular mechanisms, the metabolome was assessed by liquid chromatography‐mass spectrometry in plasma samples from MA/O adults before and after SN (80 mg/d capsules, TheraVasc, Inc.) (n=8, 59±2 yrs) or placebo (P, n=7, 61±3 yrs) (randomized, double blind). Of ~4,000 metabolites detected, significant changes in 37 intermediary metabolites were observed in SN vs. P groups (minimum 1.5 fold‐change, p<0.05). Several metabolites associated with a pro‐aging phenotype changed with SN, including pro‐inflammatory mediators and molecules related to sphingolipid, glycan, glycerophospholipid, fatty acyl, polyketide, and choline metabolism. Importantly, these SN‐induced changes occurred in the absence of changes in clinical characteristics including body composition and blood lipid profiles (all p>0.05). These preliminary results suggest that SN influences human plasma metabolome pathways linked to aging. Further targeted analysis will allow the identification of novel biomarkers in metabolic pathways modulated by SN and offer insight into the mechanisms by which SN improves specific domains of physiological function in MA/O adults.

Grant Funding Source: Supported by NIH HL107105, RR025780, AG000279
Sodium taste elicits ATP secretion in mouse taste buds (LB71)
Authors: Huang Anthony , Wu Sandy , Roper Stephen
Published: June 2021

Taste buds contain two types of cells that directly participate in gustatory transduction‐‐ Receptor (Type II) and Presynaptic (Type III) cells. Receptor cells respond to sweet, bitter and umami taste stimulation. Presynaptic cells have been identified with confidence as sour (acid) taste‐sensing cells. Using confocal Ca2+ imaging in a lingual slice preparation, Tomchik et al. (2007) showed that some vallate taste cells responded to salt (Na+) taste. Recently, ion channels (ENaC) believed to underlie salt taste transduction were reported to be in taste cells that were neither Receptor (Type II) or Presynaptic (Type III) cells. Yet, mechanisms of Na+ taste transduction and the identity of the cells that respond to Na+ stimulation remain controversial. Using Ca2+ imaging on isolated mouse vallate taste cells loaded with Fura 2, we demonstrate here that a subset of cells, neither Receptor nor Presynaptic cells, show Ca2+ mobilization in response to Na+ stimulation. Removing extracellular Ca2+ had no effect on responses evoked by Na+ stimulation. In marked contrast, applying 1 μM thapsigargin, a SER Ca‐ATPase inhibitor, or 10 μM U73122, a PLC blocker, eliminated Na+ responses, suggesting that Na+ stimulation triggers PLC/IP3‐mediated release of Ca2+ from intracellular stores. Next, we used CHO cells expressing P2X receptors as biosensors to monitor ATP release from taste buds and isolated taste cells. Na+ stimulation elicited robust biosensor responses that were blocked by suramin, confirming that Na+ stimulation elicits ATP secretion from taste buds/cells. Carbenoxolone (5 μM) or probenecid (250 μM), blockers of pannexin1 hemichannels, reversibly blocked Na‐evoked ATP secretion. Our data indicate that salt taste stimulus triggers a dedicated population of taste cells to secrete ATP via pannexin1hemmichannels.

Grant Funding Source: Supported by SIUSOM and NIH/NIDCD DC007630
TRAF6 is critical for Satellite cell function and skeletal muscle regeneration upon injury (LB815)
Authors: Hindi Sajedah , Kumar Ashok
Published: June 2021

Skeletal muscle satellite cells are a subpopulation of muscle‐stem cells responsible for carrying out muscle regenerative events. Paired box‐protein Pax7 has been shown to be indispensable for driving proper regeneration as well as supplementing the reservoir of satellite‐cell pool. However, signaling mechanisms that regulate the expression of Pax7 remain less understood. In the present study, we demonstrate that TNF receptor‐associated factor 6 (TRAF6) positively regulates the expression of Pax7 in vivo and in vitro. Deletion of TRAF6 under a tamoxifen‐induced Pax7 promoter led to profound muscle regeneration defects following BaCl2‐mediated injury. Regenerating muscle of tamoxifen‐administered mice failed to up‐regulate Pax7 and displayed a significant reduction in Myf5 transcript levels with no effect on MyoD, myogenin, Mhc3 and Mhc4 compared with vehicle‐administered mice. Similarly, cultured muscle progenitors lacking TRAF6 also displayed a significant reduction in Pax7 expression limiting their proliferative capacity. Deletion of TRAF6 had no effect on myotube formation when cells where plated at high density. Collectively, our study reveals an unprecedented requirement of TRAF6 in regulating Pax7 function in adult skeletal muscle.

Grant Funding Source: Supported by NIH R01AR059810
Autophagy Induction in AC‐16 Human Cardiomyocytes: Effects of Resveratrol and Rapamycin (LB835)
Authors: Balagopal Gauthami , Kim Jae‐Sung , Leeuwenburgh Christiaan
Published: June 2021

Mitochondrial dysfunction and increased oxidative stress contribute to the deterioration of cardiomyocyte and heart function with advancing age. Autophagy is the process by which damaged mitochondria are removed from cells. Increasing autophagy may help reverse some detrimental effects of aging on the heart. We tested the hypothesis that resveratrol, a plant polyphenol, and rapamycin, an immunosuppressant, will induce autophagy in the AC‐16 human cardiomyocytes (AC‐16 HC) independently and in combination will produce synergistic and/or additive effects.

AC‐16 HC cells were incubated for 24 hours with resveratrol (50uM), rapamycin (1uM) and a 1:1 combination of the two treatments. Induction of autophagy was assessed by protein concentration and western blot analysis using the autophagy indicator LC3B antibody. ImageLab densitometry software was used to assess the band intensity.

Treatment of the cells with the respective concentrations of resveratrol and rapamycin resulted in the up‐regulation of autophagy in the AC‐16 HC cells. The combination approach showed a modest upregualtion, but there was no significant synergistic effect.

Taken together, resveratrol and rapamycin independently and in combination have up‐regulated autophagy in the AC‐16 HC cells. The dose response of resveratrol and rampamycin on the induction of autophagy and the optimum functional or physiological concentration required for in‐vivo changes remain to be determined. The optimum exposure time coursemust also be determined to optimize the duration of increased autophagy flux. Future studies are needed to optimize and fully understand the role of resveratrol and rampamycin through autophagy in human cardiomyocytes.

Grant Funding Source: Supported by: HHMI‐Science for Life Program and NIH/NIA P30 AG028740
Vasopressin induces apical aquaporin‐2 trafficking via mal2‐mediated transcytosis in renal collecting duct cells (LB840)
Authors: Chen Pei‐Yu , Yu Ming‐Jiun
Published: June 2021

In kidney collecting duct cells, vasopressin (AVP) triggers redistribution of aquaporin‐2 (AQP2) water channel protein from intracellular vesicles to the apical plasma membrane to regulate renal water excretion. In our previous proteomic study, we identified Mal2, a lipid‐raft membrane protein known to mediate apical membrane protein trafficking via transcytosis. This study examined roles of Mal2 in AVP‐induced apical AQP2 trafficking via transcytosis. Time course immunofluorescence showed staining of AQP2 in the apical as well as the lateral plasma membrane of the mpkCCD cells after AVP stimulation. The lateral AQP2 staining disappeared gradually with concomitant appearance of apical AQP2 staining, suggesting both direct and indirect mechanisms for apical AQP2 targeting upon AVP stimulation. When the lateral membrane was fixed with tannic acid, a portion of AQP2 accumulated in the lateral space of the cells in response to AVP or forskolin, consistent with an indirect apical AQP2 targeting mechanism via transcytosis upon AVP or forskolin stimulation. The AVP or forskolin‐induced lateral AQP2 staining in the presence of tannic acid was completely absent in the cells lacking Mal2. Our data are compatible with a role of Mal2 in AVP‐induced indirect apical AQP2 targeting via the transcytotic mechanism.

Grant Funding Source: Supported by 101‐2320‐B‐002‐038‐MY3, NSC TAIWAN
Modeling of PTF1‐J and PTF1‐L Heterotrimeric Transcription Factor Complexes (LB87)
Authors: Pedigo KK , Mainali Rabina , Glispin Christopher , Noble Gabe , Petters Garrett , Allmam Casey , Agua Alec Agua , Bauzaldua Adrian , Crane Ben , Aranoff Max , Gonzales Nicholas , Park Christine , Chung Elizabeth , Montoux Amy , Flabiano Meredith , Espinosa Anika , Almazan Selena , Kaye Cassidy , Crowling Anna , Chandler Chandria , Allman Julianna , Coats Ward , MacDonald Raymond
Published: June 2021

Students in Biomedical Research Studies at Hillcrest High School in Dallas, Texas participate in an ongoing research program at the University of Texas Southwestern Medical Center to study the structure and function of a transcription factor complex. Ptf1a is a transcription factor that is crucial to the development of the embryonic pancreas. Its functional form is in a trimeric complex composed of a heterodimer of E12/E47 and Ptf1a (basic helix‐loop‐helix transcription factors), and either Rbpj or Rbpjl (paralogs, also present in Notch signaling). The Rbpj form of the complex (PTF1‐J) is required for the early stage of pancreatic development. Subsequently, the Rbpjl‐form (PTF1‐L) is required for the formation of mature acinar cells of the exocrine pancreas. The Hillcrest SMART (Students Modeling A Research Topic) Team using 3D printing technology has generated models for the PTF1‐J and PTF1‐L transcription factor complexes. The models provide the orientation of the Ptf1a/E12 heterodimer relative to the Rbpj and Rbpjl proteins and characterizes interactions formed between Ptf1a (tryptophan 298) and a hydrophobic pocket present in the b‐trefoil domain of Rbpj or Rbpjl. Determination of the structures for the PTF1‐J and PTF1‐L complexes will help elucidate the structural determinants and the mechanism for the strong cooperative DNA binding of these complexes.

Grant Funding Source: Supported by a grant from NIH‐SEPA and NIH‐CTSA.
Discordance Between Respiratory Drive and Sedation Depth in Critically Ill Patients Receiving Mechanical Ventilation*
Authors: Dzierba Amy L. , Khalil Anas M. , Derry Katrina L. , Madahar Purnema , Beitler Jeremy R.
Published: June 2021

OBJECTIVES:

In mechanically ventilated patients, deep sedation is often assumed to induce “respirolysis,” that is, lyse spontaneous respiratory effort, whereas light sedation is often assumed to preserve spontaneous effort. This study was conducted to determine validity of these common assumptions, evaluating the association of respiratory drive with sedation depth and ventilator-free days in acute respiratory failure.

DESIGN:

Prospective cohort study.

SETTING:

Patients were enrolled during 2 month-long periods in 2016–2017 from five ICUs representing medical, surgical, and cardiac specialties at a U.S. academic hospital.

Patients:

Eligible patients were critically ill adults receiving invasive ventilation initiated no more than 36 hours before enrollment. Patients with neuromuscular disease compromising respiratory function or expiratory flow limitation were excluded.

INTERVENTIONS:

Respiratory drive was measured via P0.1, the change in airway pressure during a 0.1-second airway occlusion at initiation of patient inspiratory effort, every 12 ± 3 hours for 3 days. Sedation depth was evaluated via the Richmond Agitation-Sedation Scale. Analyses evaluated the association of P0.1 with Richmond Agitation-Sedation Scale (primary outcome) and ventilator-free days.

MEASUREMENTS AND MAIN RESULTS:

Fifty-six patients undergoing 197 bedside evaluations across five ICUs were included. P0.1 ranged between 0 and 13.3 cm H2O (median [interquartile range], 0.1 cm H2O [0.0–1.3 cm H2O]). P0.1 was not significantly correlated with the Richmond Agitation-Sedation Scale (R
Spearman, 0.02; 95% CI, –0.12 to 0.16; p = 0.80). Considering P0.1 terciles (range less than 0.2, 0.2–1.0, and greater than 1.0 cm H2O), patients in the middle tercile had significantly more ventilator-free days than the lowest tercile (incidence rate ratio, 0.78; 95% CI, 0.65–0.93; p < 0.01) or highest tercile (incidence rate ratio, 0.58; 95% CI, 0.48–0.70; p < 0.01).

CONCLUSIONS:

Sedation depth is not a reliable marker of respiratory drive during critical illness. Respiratory drive can be low, moderate, or high across the range of routinely targeted sedation depth.
Loop colostomy to relieve debilitating chronic constipation in spina bifida patients: a case report
Authors: Kale Supriya V. , Chaudhry Arooj F. , Wazir Hersh , Yansen Michael , Tiesenga Frederick
Published: June 2021

Introduction and importance:

Spina bifida often results in neurogenic bowel dysfunction due to the loss of sensory and motor control of the gastrointestinal tract. This dysfunction further leads to the difficulty of emptying the bowel, resulting in constipation. Therefore, a complication of spina bifida is chronic constipation. Long-standing constipation greatly affects the quality of life. Chronic constipation leads to loss of social and work opportunities, causes severe discomfort, and increases the potential for several secondary complications such as hemorrhoids, anal fissures, and urinary incontinence. Several treatment measures can be considered to relieve chronic constipation in order to improve the quality of life of patients with spina bifida.

Case presentation:

The purpose of this report is to present a rare case of an adult patient with spina bifida who underwent a loop colostomy procedure as a treatment option for her debilitating chronic constipation symptoms. The patient’s chronic constipation and associated symptoms led to an immense decrease in quality of life. After several failed attempts at relieving constipation, a loop colostomy procedure was conducted.

Clinical discussion:

A loop colostomy is a surgical procedure leading to exteriorization of the colon. As seen in this case, a loop colostomy can be considered as a curative option for chronic constipation specifically in patients with spina bifida. The surgical procedure alleviated chronic constipation and its associated symptoms.

Conclusion:

Chronic constipation and associated symptoms in adult patients with spina bifida can be treated with a loop colostomy procedure. This procedure is an innovative and helpful option for these specific patients. The possibility of increased quality of life in patients with impairing symptoms makes the loop colostomy procedure an optimistic treatment option.
Prognostic value of masked uncontrolled apparent resistant hypertension detected through home blood pressure monitoring
Authors: Barochiner Jessica , Aparicio Lucas S. , Martínez Rocío , Alfie José , Marín Marcos J.
Published: June 2021

Objective:

Resistant hypertension carries a poor prognosis and current guidelines recommend the exclusion of the white-coat phenomenon for proper diagnosis. However, guidelines do not focus on patients treated with at least three drugs whose blood pressure (BP) is controlled at the office but elevated out of it. We aimed at determining whether this masked uncontrolled apparent resistant hypertension (MUCRH) detected through home blood pressure monitoring (HBPM) has prognostic value for fatal and nonfatal events in these hypertensive patients.

Methods:

Hypertensive patients treated with at least three drugs who performed a baseline HBPM between 2008 and 2015 were followed to register the occurrence of total mortality, cardiovascular mortality, and fatal and nonfatal cardiac and cerebrovascular events. MUCRH was defined as office blood pressure less than 140/90 mmHg and home BP at least 135 and/or 85 mmHg. Multivariable Cox proportional hazard models were adjusted to determine the independent prognostic value of MUCRH for the events of interest.

Results:

We included 470 patients, 35.5% male, mean age 71.9 years, and treated with 3.3 antihypertensive drugs on average. Among study population, 15.5% had MUCRH (33.3% when considering only patients with adequate BP control at the office). Median follow-up was 6.7 years. In multivariable models, MUCRH was an independent predictor for cardiovascular mortality and cerebrovascular events: hazard ratio 4.9 (95% CI 1.2–19.9, P = 0.03) and 5.1 (95% CI 1.5–16.9, P = 0.01), respectively.

Conclusion:

MUCRH is not rare and is independently associated with cardiovascular morbidity and mortality. The systematic monitoring of intensively treated individuals through HBPM would be useful for the detection of patients at increased risk of events.
Efficacy, Safety, and Retreatment Benefit of Micropulse Transscleral Cyclophotocoagulation in Glaucoma
Authors: Chamard Chloé , Bachouchi Alex , Daien Vincent , Villain Max
Published: June 2021

Precis:

Micropulse transscleral cyclophotocoagulation (MP-TSCPC) with a 120-second setting reduces intraocular pressure (IOP) with a 6-month success of 45.5%. Only late (>6 mo) failure seem to present a benefit for retreatment.

Purpose:

The purpose of this study was to assess MP-TSCPC efficacy, safety, factors of success, and retreatment benefit in open-angle glaucoma.

Patients and Methods:

A retrospective consecutive case series study. We included patients with open-angle glaucoma who were naive of a cycloablative procedure and underwent MP-TSCPC at 2000 mW for 120 seconds between May 1, 2017, and October 31, 2019. Success was defined as IOP >5 and ≤21 mm Hg with IOP reduction ≥20% from baseline, without any retreatment and visual acuity better than negative light perception. MP-TSCPC retreatment was early and late, before and after 6 months postoperatively, respectively.

Results:

We included 94 eyes in 94 patients [mean (SD) age: 67.2 (13.4) y; 47.9% women]. The mean preoperative IOP was 24.9 (7.1) mm Hg and was reduced to 18.9 (6.3) at month 6 (P<0.0001). The success rate decreased progressively over time and reached 45.5% at 6 months. Patients with 6-month surgical success had lower mean axial length than others [24.1 (1.5) vs. 25.5 (2.1) mm, P=0.05]. In patients with early and late MP-TSCPC retreatment, the 6-month success rate was 16.7% and 63.6%, respectively.

Conclusions:

MP-TSCPC performed with a 120-second setting reduced IOP, with 45.5% success at month 6 and few complications. Axial length was newly described as affecting success, probably linked to the ciliary-body position. Retreatment seemed to be of little benefit in nonresponders or those with early failure. Further studies on laser settings and ciliary-body location are required to find the best risk-benefit protocol.
Undergraduate teaching of urology: Quo vadis?
Authors: Pereira Diogo , Catarino Raquel , Rodrigues Vasco , Costa Gabriel , Silva João , Carmo-Reis Frederico , Martins-Silva Carlos
Published: June 2021

Background:

The undergraduate teaching of urology is not uniform in the various European medical schools and even absent in some of them, despite the widespread adoption of the Bologna process, which advocates a standardization and harmonization of medical education. Our aim was to evaluate the perception of junior doctors about the undergraduate teaching of Urology and the exposure to the specialty of Urology in undergraduate education in Portuguese medical schools.

Methods:

A questionnaire was emailed to all physicians who first enrolled in the Board of Portuguese Doctors in 2017 and 2018. The questionnaire consisted of several questions about specialty exposure, pathology, and basic urological procedures. A database for statistical analysis was created.

Results:

One hundred and eighty-six answers were considered valid. Although almost all participant physicians attribute considerable importance to Urology specialty, most find their exposure to urological pathology and basic urological procedures to be inappropriate in medical school. Urinary lithiasis and lower urinary tract symptoms are the subjects on which doctors feel most prepared after graduating. Interestingly, 63.4% of doctors consider that the education they had in college was preponderant in choosing their specialty.

Conclusions:

The teaching of Urology in Portuguese Medical Schools is considered by junior doctors as inadequate, not reflecting the importance of this specialty in the clinical practice. These results are like those found in other countries. A reflection and consequent change of the teaching paradigm is necessary, namely at the practical teaching level.
Readiness for Hospital Discharge and Its Correlates Among People Living With HIV in Hunan, China: A Cross-sectional Study
Authors: Zhang Xiaoxia , Tang Chulei , Xiao Xueling , Sun Manman , Wang Honghong
Published: June 2021

We aimed to (a) describe the readiness for hospital discharge in people living with HIV and (b) explore factors associated with readiness for hospital discharge. A cross-sectional survey was conducted at two infectious disease hospitals in Hunan, China, from May to November 2017. The readiness for hospital discharge scale (RHDS) was used to assess discharge readiness. The average item mean for the RHDS ranges from 0 to 10, and higher scores represent a higher level of readiness for hospital discharge. The mean score of the RHDS was 7.78 (95% confidence interval 7.586–7.968), and 27.6% of participants (n = 56/203) felt unready for discharge (RHDS <7). We found that older age, lack of medical insurance, lower self-rated health status, poorer quality of discharge teaching, and more severe depressive symptoms were significantly associated with a lower level of readiness for hospital discharge. Interventions are needed to improve readiness of people living with HIV for hospital discharge in Hunan, China, especially for those of advanced age, without medical insurance, with worse self-rated health status, and those with higher levels of depressive symptoms.
Criminalization of Sexual and Gender Minorities and Its Consequences for the HIV Epidemic in Zambia: A Critical Review and Recommendations
Authors: Yelverton Valerie , Qiao Shan , Menon J. Anitha , Ngosa Levy , Kabwe McLean , Harrison Sayward , Weissman Sharon , Li Xiaoming , W. Harper Gary
Published: June 2021

To elaborate the negative impacts of sexual and gender minority (SGM)-related legislation for the HIV epidemic in Zambia, we reviewed Zambian legislation that restricts the rights of SGM people and synthesized its consequences. We retrieved legal documents through the National Assembly of Zambia and the Zambia Legal Information Institute and conducted a critical review based on four academic databases following thematic synthesis methodology. Eighteen literature records and six Zambian laws were included in the review. Existing laws criminalize same-sex sexual behavior and restrict same-sex marriage and the adoption of children. Anti-SGM legislation has limited legal protections for SGM people and increased vulnerability of criminal prosecution and HIV exposure, persistent stigma/discrimination, insufficient public health resources, and lessened access to HIV-related services. We recommend enacting legal protections for SGM people, decriminalizing anti-SGM laws, rectifying misinformation to destigmatize SGM people, targeting health care for SGM people, and including SGM people in the national HIV strategy.
Clinical Utility of Anchored Multiplex Solid Fusion Assay for Diagnosis of Bone and Soft Tissue Tumors
Authors: Chebib Ivan , Taylor Martin S. , Nardi Valentina , Rivera Miguel N. , Lennerz Jochen K. , Cote Gregory M. , Choy Edwin , Lozano Calderón Santiago A. , Raskin Kevin A. , Schwab Joseph H. , Mullen John T. , Chen Yen-Lin E. , Hung Yin P. , Nielsen Gunnlaugur P. , Deshpande Vikram
Published: June 2021

Sarcoma diagnosis has become increasingly complex, requiring a combination of morphology, immunohistochemistry, and molecular studies to derive specific diagnoses. We evaluated the role of anchored multiplex polymerase chain reaction–based gene fusion assay in sarcoma diagnostics. Between 2015 and 2018, bone and soft tissue sarcomas with fusion assay results were compared with the histologic diagnosis. Of 143 sarcomas tested for fusions, 43 (30%) had a detectable fusion. In review, they could be classified into 2 main categories: (1) 31 tumors with concordant morphologic and fusion data; and (2) 12 tumors where the fusion panel identified an unexpected rearrangement that played a significant role in classification. The overall concordance of the fusion assay results with morphology/immunohistochemistry or alternate confirmatory molecular studies was 83%. Collectively, anchored multiplex polymerase chain reaction–based solid fusion assay represents a robust means of detecting targeted fusions with known and novel partners. The predictive value of the panel is highest in tumors that show a monomorphic cell population, round cell tumors, as well as tumors rich in inflammatory cells. However, with an increased ability to discover fusions of uncertain significance, it remains essential to emphasize that the diagnosis of bone and soft tissue neoplasms requires the integration of morphology and immunohistochemical profile with these molecular methods, for accurate diagnosis and optimal clinical management of sarcomas.
Hereditary Spherocytosis as an Atypical Presentation of Anemia in Ulcerative Colitis
Authors: Cho Moo , Tucker Suzanne , Choi Lillian
Published: June 2021

Anemia is encountered in up to two-thirds of all patients with inflammatory bowel disease (IBD). We are reporting a case of a 9-year-old female with history of very early onset IBD ulcerative colitis, and primary sclerosing cholangitis who was found to have hereditary spherocytosis as the etiology of her anemia. Despite good clinical response to IBD therapy, she continued to have persistent normocytic anemia. Liver biopsy and magnetic resonance cholangiopancreatography for uptrending liver transaminases demonstrated iron deposition which led to a T2-weighted magnetic resonance imaging study that quantified significant iron deposition in her liver and kidneys. Without any history of blood transfusions, these findings were concerning for hereditary hemochromatosis, but the hereditary hemochromatosis gene test was negative. Whole genome sequencing identified a pathogenic de novo variant consistent with hereditary spherocytosis.

Table of Contents Summary:

A novel presentation of anemia in inflammatory bowel disease
Intussusception Caused by Percutaneous Endoscopic Gastrostomy With Jejunal Extension in Patients With Severe Motor and Intellectual Disabilities
Authors: Hagiwara Shin-ichiro , Maeyama Takatoshi , Honma Hitoshi , Soh Hideki , Usui Noriaki , Etani Yuri
Published: June 2021

The risk of intussusception related to percutaneous endoscopic gastrostomy with jejunal extension (PEG-J) in patients with severe motor and intellectual disabilities (SMID) remains unknown. In a cross-sectional study, a review of 26 patients (mean age, 11.6 ± 6.4 years) with SMID who underwent PEG-J was performed. During the follow-up period, 6 of 26 (23%) patients developed intussusception. The median period from PEG-J to the onset of intussusception was 364 (range, 8–1344) days. No significant difference was observed in the Cobb angle between the intussusception and nonintussusception groups; however, body mass index at the time of PEG-J was significantly lower in the intussusception group. Intussusception related to PEG-J occurs relatively frequently in patients, and it is possibly attributable to factors such as deformity caused by undernutrition and weight loss. If enteral nutrition via PEG-J has been established, earlier enterostomy can be recommended because of the high risk of intussusception in patients with SMID.
18F-Choline PET/CT, MRI, and Software-Based Image Fusion Analysis in Patients With Primary Hyperparathyroidism
Authors: Hofer Thomas , Kronbichler Juergen , Huber Helmut , Hergan Benedikt , Kaiser Bernhard , Shamiyeh Andreas , Fellner Franz , Gabriel Michael
Published: June 2021

Purpose

The aim of this study was to evaluate the diagnostic performance of 18F-choline PET and MRI in patients with primary hyperparathyroidism. Furthermore, the additional value of software-based PET/MRI scan fusion was analyzed.

Patients and Methods

This retrospective study includes 42 patients (38 women) with an age between 32.5 and 79.1 years. PET/CT scans were performed on a dedicated system after injection of 250 to 350 MBq 18F-choline. For the MRI examination, T1-weighted images of the cervical region were used. The image fusion was made by anatomical coregistration using an automated algorithm based on mutual information.

Results

A total of 46 lesions were discovered and histologically confirmed in 42 patients. Histopathological examination revealed 38 adenomas and 8 hyperplasias. This means that, in 4 of these 42 patients, 2 lesions per patient were discovered. PET/CT also detected 46 abnormal findings, but only 43 were correctly recognized, whereas the other 3 were false-positive (FP). Six lesions could not be detected correctly: 3 were FP and 3 false-negative, which resulted in a sensitivity of 93.5% and a specificity of 97.5%. The site-specific evaluation showed 18 true-positive enlarged parathyroid glands with MRI, but also produced 13 FP findings and failed to detect 28 lesions; the sensitivity and specificity are thus 39.1% and 89.3%, respectively. The difference in detection rate between 18F-choline PET/CT and MRI was statistically significant (P < 0.001).

Conclusions

18F-choline PET/CT is clearly superior to MRI for localization diagnostics in primary hyperparathyroidism. Image fusion of both modalities can be helpful for more precise anatomical assignment.
FDG PET/CT in Isolated Spermatic Cord Metastasis From Colon Cancer
Authors: Ji Xia , Dong Aisheng
Published: June 2021

Isolated spermatic cord metastasis is extremely rare. We describe FDG PET/CT findings in a case of isolated spermatic cord metastasis from colon cancer detected 27 months after colectomy. The tumor showed intense focal FDG uptake in the right spermatic cord mimicking a primary spermatic cord malignancy.
Temperature and pathogen exposure act independently to drive host phenotypic trajectories
Authors: Hector Tobias E. , Sgrò Carla M. , Hall Matthew D.
Published: June 2021

Natural populations are experiencing an increase in the occurrence of both thermal stress and disease outbreaks. How these two common stressors interact to determine host phenotypic shifts will be important for population persistence, yet a myriad of different traits and pathways are a target of both stressors, making generalizable predictions difficult to obtain. Here, using the host
Daphnia magna
and its bacterial pathogen
Pasteuria ramosa
, we tested how temperature and pathogen exposure interact to drive shifts in multivariate host phenotypes. We found that these two stressors acted mostly independently to shape host phenotypic trajectories, with temperature driving a faster pace of life by favouring early development and increased intrinsic population growth rates, while pathogen exposure impacted reproductive potential through reductions in lifetime fecundity. Studies focussed on extreme thermal stress are increasingly showing how pathogen exposure can severely hamper the thermal tolerance of a host. However, our results suggest that under milder thermal stress, and in terms of life-history traits, increases in temperature might not exacerbate the impact of pathogen exposure on host performance, and vice versa.
Expanded host and geographic range of tadpole associations with the Severe Perkinsea Infection group
Authors: Smilansky Vanessa , Jirků Miloslav , Milner David S. , Ibáñez Roberto , Gratwicke Brian , Nicholls Andrew , Lukeš Julius , Chambouvet Aurélie , Richards Thomas A.
Published: June 2021

Severe Perkinsea infection is an emerging disease of amphibians, specifically tadpoles. Disease presentation correlates with liver infections of a subclade of Perkinsea (Alveolata) protists, named Pathogenic Perkinsea Clade (PPC). Tadpole mortality events associated with PPC infections have been reported across North America, from Alaska to Florida. Here, we investigate the geographic and host range of PPC associations in seemingly healthy tadpoles sampled from Panama, a biogeographic provenance critically affected by amphibian decline. To complement this work, we also investigate a mortality event amongHyla arboreatadpoles in captive-bred UK specimens. PPC SSU rDNA was detected in 10 of 81 Panama tadpoles tested, andH. arboreatadpoles from the UK. Phylogenies of the Perkinsea SSU rDNA sequences demonstrate they are highly similar to PPC sequences sampled from mortality events in the USA, and phylogenetic analysis of tadpole mitochondrial SSU rDNA demonstrates, for the first time, PPC associations in diverse hylids. These data provide further understanding of the biogeography and host range of this putative pathogenic group, factors likely to be important for conservation planning.
Discontinued alcohol consumption elicits withdrawal symptoms in honeybees
Authors: Ostap-Chec Monika , Opalek Monika , Stec Daniel , Miler Krzysztof
Published: June 2021

The honeybee continues to be developed as a model species in many research areas, including studies related to the effects of alcohol. Here, we investigate whether workers display one of the key features of alcoholism, namely withdrawal symptoms. We show that workers fed for a prolonged time on food spiked with ethanol, after discontinuation of access to such food, exhibited a marked increase in the consumption of ethanol and a slight increase in mortality. We additionally show that withdrawal symptoms do not include an increase in appetitiveness of ethanol diluted in water. Our results demonstrate that workers can develop alcohol dependence, which might be especially important in the natural setting of repeated exposure to ethanol in floral nectar and for their potential as a model of alcohol addiction.
FGGA-lnc: automatic gene ontology annotation of lncRNA sequences based on secondary structures
Authors: Spetale Flavio E. , Murillo Javier , Villanova Gabriela V. , Bulacio Pilar , Tapia Elizabeth
Published: June 2021

The study of long non-coding RNAs (lncRNAs), greater than 200 nucleotides, is central to understanding the development and progression of many complex diseases. Unlike proteins, the functionality of lncRNAs is only subtly encoded in their primary sequence. Current in-silico lncRNA annotation methods mostly rely on annotations inferred from interaction networks. But extensive experimental studies are required to build these networks. In this work, we present a graph-based machine learning method called FGGA-lnc for the automatic gene ontology (GO) annotation of lncRNAs across the three GO subdomains. We build upon FGGA (factor graph GO annotation), a computational method originally developed to annotate protein sequences from non-model organisms. In the FGGA-lnc version, a coding-based approach is introduced to fuse primary sequence and secondary structure information of lncRNA molecules. As a result, lncRNA sequences become sequences of a higher-order alphabet allowing supervised learning methods to assess individual GO-term annotations. Raw GO annotations obtained in this way are unaware of the GO structure and therefore likely to be inconsistent with it. The message-passing algorithm embodied by factor graph models overcomes this problem. Evaluations of the FGGA-lnc method on lncRNA data, from model and non-model organisms, showed promising results suggesting it as a candidate to satisfy the huge demand for functional annotations arising from high-throughput sequencing technologies.
Alignments of biomolecular contact maps
Authors: Stadler Peter F.
Published: June 2021

Alignments of discrete objects can be constructed in a very general setting as super-objects from which the constituent objects are recovered by means of projections. Here, we focus on contact maps, i.e. undirected graphs with an ordered set of vertices. These serve as natural discretizations of RNA and protein structures. In the general case, the alignment problem for vertex-ordered graphs is NP-complete. In the special case of RNA secondary structures, i.e. crossing-free matchings, however, the alignments have a recursive structure. The alignment problem then can be solved by a variant of the Sankoff algorithm in polynomial time. Moreover, the tree or forest alignments of RNA secondary structure can be understood as the alignments of ordered edge sets.
Glioblastoma multiforme: a multi-omics analysis of driver genes and tumour heterogeneity
Authors: Herrera-Oropeza Gabriel Emilio , Angulo-Rojo Carla , Gástelum-López Santos Alberto , Varela-Echavarría Alfredo , Hernández-Rosales Maribel , Aviña-Padilla Katia
Published: June 2021

Glioblastoma (GBM) is the most aggressive and common brain cancer in adults with the lowest life expectancy. The current neuro-oncology practice has incorporated genes involved in key molecular events that drive GBM tumorigenesis as biomarkers to guide diagnosis and design treatment. This study summarizes findings describing the significant heterogeneity of GBM at the transcriptional and genomic levels, emphasizing 18 driver genes with clinical relevance. A pattern was identified fitting the stem cell model for GBM ontogenesis, with an upregulation profile for
MGMT
and downregulation for
ATRX, H3F3A, TP53
and
EGFR
in the mesenchymal subtype. We also detected overexpression of
EGFR, NES, VIM
and
TP53
in the classical subtype and of
MKi67
and
OLIG2
genes in the proneural subtype. Furthermore, we found a combination of the four biomarkers
EGFR, NES, OLIG2
and
VIM
with a remarkable differential expression pattern which confers them a strong potential to determine the GBM molecular subtype. A unique distribution of somatic mutations was found for the young and adult population, particularly for genes related to DNA repair and chromatin remodelling, highlighting
ATRX, MGMT
and
IDH1.
Our results also revealed that highly lesioned genes undergo differential regulation with particular biological pathways for young patients. This multi-omic analysis will help delineate future strategies related to the use of these molecular markers for clinical decision-making in the medical routine.
Bioinformatics in Latin America: ISCB-LA SOIBIO RMB Symposium 2020
Authors: Hernández-Rosales M.
Published: June 2021

This special issue ‘Bioinformatics in Latin America: ISCB-LA SOIBIO RMB Symposium 2020’ features the papers presented at the ISCB-LA SoIBio BioNetMX 2020 Virtual Symposium held on 28–29 October 2020. This is the first international joint event organized by the Mexican Network for Bioinformatics (RMB), the International Society of Computational Biology (ISCB) and the Iberoamerican Society for Bioinformatics (SOIBIO). The aim of this event is to foster interdisciplinary and multidisciplinary collaborations in research across Exact and Life Sciences.