bluuebunny/crossref_metadata_2025 huggingface dataset:
Milstein schemes and antithetic multilevel Monte Carlo sampling for delay McKean–Vlasov equations and interacting particle systems
Authors: Bao Jianhai , Reisinger Christoph , Ren Panpan , Stockinger Wolfgang
Published: September 2023

In this paper, we first derive Milstein schemes for an interacting particle system associated with point delay McKean–Vlasov stochastic differential equations, possibly with a drift term exhibiting super-linear growth in the state component. We prove strong convergence of order one and moment stability, making use of techniques from variational calculus on the space of probability measures with finite second-order moments. Then, we introduce an antithetic multilevel Milstein scheme, which leads to optimal complexity estimators for expected functionals of solutions to delay McKean–Vlasov equations without the need to simulate Lévy areas.
Predictors of users’ adherence to a fully automated digital intervention to manage insomnia complaints
Authors: Sanchez-Ortuno Maria Montserrat , Pecune Florian , Coelho Julien , Micoulaud-Franchi Jean Arthur , Salles Nathalie , Auriacombe Marc , Serre Fuschia , Levavasseur Yannick , de Sevin Etienne , Sagaspe Patricia , Philip Pierre
Published: September 2023

Objective

Fully automated digital interventions show promise for disseminating evidence-based strategies to manage insomnia complaints. However, an important concept often overlooked concerns the extent to which users adopt the recommendations provided in these programs into their daily lives. Our objectives were evaluating users’ adherence to the behavioral recommendations provided by an app, and exploring whether users’ perceptions of the app had an impact on their adherence behavior.

Material and methods

Case series study of individuals completing a fully automated insomnia management program, conducted by a virtual agent, during December 2020 to September 2022. Primary outcome was self-reported adherence to the behavioral recommendations provided. Perceptions of the app and of the virtual agent were measured with the Acceptability E-Scale and ECA-Trust Questionnaire. Insomnia was evaluated with the Insomnia Severity Index at baseline (phase 1), after 7 days of sleep monitoring (phase 2) and post-intervention (phase 3).

Results

A total of 824 users were included, 62.7% female, mean age 51.85 (±12.55) years. Of them, 32.7% reported having followed at least one recommendation. Users’ trust in the virtual agent and acceptance of the app were related to a pre-intervention effect in insomnia severity (phase 2). In turn, larger pre-intervention improvements predicted better adherence. Mediational analyses showed that higher levels of trust in the virtual agent and better acceptance of the app exerted statistically significant positive effects on adherence (β = 0.007, 95% CI, 0.001-0.017 and β = 0.003, 95% CI 0.0004-0.008, respectively).

Discussion

Users’ adherence is motivated by positive perceptions of the app’s features and pre-intervention improvements.

Conclusions

Determinants of adherence should be assessed, and targeted, to increase the impact of fully automated digital interventions.
Validation of an Innovative Chromatographic Method for Hypericin Quantification in Nanostructured Lipid Carriers
Authors: de Araújo Patricia Rocha , Sato Mariana Rillo , Luiz Marcela Tavares , Chorilli Marlus
Published: September 2023

Background

Hypericin (HYP) is a natural compound widely used as a food supplement. The encapsulation of HYP into nanosystems, such as nanostructured lipid carriers (NLC), is a promising strategy for delivering this lipophilic molecule and protecting it from degradation.

Objective

This study aims to develop and validate an analytical method to quantify the encapsulation efficiency of HYP in NLC.

Method

A reverse-phase high-performance liquid chromatography (HPLC) method was developed and validated according to the International Conference on Harmonization (ICH) guide Q2 (R1). NLC was prepared through the ultrasonication method, and HYP encapsulation efficiency was evaluated using the validated method.

Results

Separation was achieved using an isocratic mobile phase composed of acetonitrile, methanol, and ammonium acetate buffer (10 mM, pH 5.0) (54:36:10, v/v/v) and a reverse stationary phase. The specificity, linearity, precision, accuracy, and robustness of the method were assessed and confirmed during the validation. Furthermore, the validated method was able to determine the encapsulation efficiency of HYP in NLC.

Conclusions

The HPLC method was validated, and the results indicated the ability of NLC to deliver HYP compounds for further application as a food supplement.

Highlights

HYP is used as a food supplement and for photodynamic therapy (PDT). The developed method was specific, linear, precise, accurate, and robust. NLCs showed a high ability to encapsulate HYP.
Impact of methemoglobin on carboxyhemoglobin saturation measurement in fatal sodium nitrate and sodium nitrite cases
Authors: Desrosiers Nathalie A , Chow Betty L.C
Published: September 2023

An increase in suicide cases by sodium nitrate and sodium nitrite ingestion has been noted in the scientific literature. We report on the possible impact of nitrate/nitrite-caused methemoglobinemia on carboxyhemoglobin measurement by spectrophotometric methods. Elevated methemoglobin saturation may result in insufficient reducing agents to convert methemoglobin into deoxygenated hemoglobin, affecting the measured total hemoglobin and carboxyhemoglobin saturation. We highlight four cases where the cause of death was attributed to sodium nitrate or sodium nitrite ingestion. The possible impact of the nitrate/nitrite-caused methemoglobinemia on the carboxyhemoglobin saturation as measured by spectrophotometry is discussed. Further studies are needed to identify a causal relationship between nitrate/nitrite-caused methemoglobinemia and carboxyhemoglobin saturation as measured by spectrophotometric methods.
More than Lack of Capacity: Active Impunity in Mexico
Authors: Anaya-Muñoz Alejandro , Cruz-Marín Patricia , Cavallaro James
Published: September 2023

Mexico faces a severe crisis of violations of physical integrity rights. In the past fifteen years, hundreds of thousands of people have been killed, over one hundred thousand have disappeared, and torture continues to be widespread. Observers emphasize the role of impunity as a critical causal factor. Negligence and lack of capacity have been considered as causes of impunity. This article elaborates the role of ‘active impunity’, understood as the deliberate efforts by investigative authorities to undermine criminal investigations on cases of human rights violations. Observing 12 cases of violations of physical integrity rights in Mexico, occurring between 2008 and 2021 in seven states of the country, the article shows that active impunity takes place and identifies some of the mechanism through which it is produced.
Potential Benefits of Expanded Palivizumab in American Indian Children Under the Age of 2 Years
Authors: Close Ryan M , Palmer Alvin S , McAuley James B
Published: September 2023

Severe respiratory syncytial virus (RSV) infections disparately impact American Indian communities. We implemented a program that expanded palivizumab to all children under 2 years of age that led to significant reductions in RSV infections and hospitalizations for both high-risk and non-high-risk recipients in a rural American Indian community in Eastern Arizona.
A mass conundrum
Authors: Kendric Tan Jun Guang , Thomas Sabu
Published: September 2023

A 30-year-old female presented to a rural hospital in Western Australia complaining of generalized abdominal pain and symptoms of partial bowel obstruction. Computed tomography (CT) showed a radiological ‘whirl’ sign, with images 4 years apart demonstrating interval progression. Given our patient’s past history with miliary tuberculosis, we performed a diagnostic laparotomy which confirmed omental torsion. We report a case of surgically and pathologically proven chronic secondary omental torsion presenting with partial bowel obstruction, and showcase rarely seen interval progression on CT.
Different higher order kinematics between star-forming and quiescent galaxies based on the SAMI, MAGPI, and LEGA-C surveys
Authors: D’Eugenio Francesco , van der Wel Arjen , Derkenne Caro , van Houdt Josha , Bezanson Rachel , Taylor Edward N , van de Sande Jesse , Baker William M , Bell Eric F , Bland-Hawthorn Joss , Bluck Asa F L , Brough Sarah , Bryant Julia J , Colless Matthew , Cortese Luca , Croom Scott M , van Dokkum Pieter , Fisher Deanne , Foster Caroline , Fraser-McKelvie Amelia , Gallazzi Anna , de Graaff Anna , Groves Brent , del P. Lagos Claudia , Looser Tobias J , Maiolino Roberto , Maseda Michael , Mendel J Trevor , Nersesian Angelos , Pacifici Camilla , Piotrowska Joanna M , Poci Adriano , Remus Rhea-Silvia , Sharma Gauri , Sweet Sarah M , Thater Sabine , Tran Kim-Vy , Übler Hannah , Valenzuela Lucas M , Wisnioski Emily , Zibetti Stefano
Published: September 2023

We present the first statistical study of spatially integrated non-Gaussian stellar kinematics spanning 7 Gyr in cosmic time. We use deep, rest-frame optical spectroscopy of massive galaxies (stellar mass $M_\star \gt 10^{10.5} \, \mathrm{M_\odot }$) at redshifts z = 0.05, 0.3, and 0.8 from the SAMI, MAGPI, and LEGA-C surveys, to measure the excess kurtosis h4 of the stellar velocity distribution, the latter parametrized as a Gauss–Hermite series. We find that at all redshifts where we have large enough samples, h4 anticorrelates with the ratio between rotation and dispersion, highlighting the physical connection between these two kinematic observables. In addition, and independently from the anticorrelation with rotation-to-dispersion ratio, we also find a correlation between h4 and M⋆, potentially connected to the assembly history of galaxies. In contrast, after controlling for mass, we find no evidence of independent correlation between h4 and aperture velocity dispersion or galaxy size. These results hold for both star-forming and quiescent galaxies. For quiescent galaxies, h4 also correlates with projected shape, even after controlling for the rotation-to-dispersion ratio. At any given redshift, star-forming galaxies have lower h4 compared to quiescent galaxies, highlighting the link between kinematic structure and star-forming activity.
Testing the planetary hypothesis of NY Virginis: anticipated change in the eclipse timing trend within the next five years
Authors: Esmer Ekrem Murat , Baştürk Özgür , Selam Selim Osman
Published: September 2023

Regarding the recent debate about the potential circumbinary exoplanets around NY Virginis (NY Vir), we analysed mid-eclipse timings of NY Vir using archival photometric data as well as our own observations and the ones from TESS. For this purpose, we first modelled the available eclipse light curves of the binary system to determine the masses of the stars. Then, we measured mid-eclipse times by fitting the light-curve model cycle-to-cycle to the light curves from TESS and our observations. By fitting a Newtonian eclipse timing model to the data, which takes both the light-time effect and potential mutual gravitational interactions into account, we derived orbital parameters and masses of the potential circumbinary planets assuming both eccentric and circular orbits. The models without a quadratic term that can model any possible secular trend, converged to comparable results. Dynamical stability tests show that our Newtonian timing solution corresponds to stable orbital configurations for two circumbinary planets with masses ∼2.3 and ∼4.0 MJup in orbits with very low eccentricity. Our analyses show that the addition of quadratic term for modelling the eclipse timing variation may induce the planetary orbits to be eccentric, hence more likely to be unstable. According to our findings, an upward trend in the eclipse timings followed by a downward one within the next five years is expected due to binary motion induced by circumbinary planets.
Modelling of the multitransition periodic flaring in G9.62+0.20E
Authors: Rajabi F , Houde M , MacLeod G C , Goedhart S , Tanabe Y , van den Heever S P , Wyenberg C M , Yonekura Y
Published: September 2023

We present detailed modelling of periodic flaring events in the 6.7 GHz and 12.2 GHz methanol lines as well as the OH 1665 MHz and 1667 MHz transitions observed in the G9.62+0.20E star-forming region. Our analysis is performed within the framework of the one-dimensional Maxwell–Bloch equations, which intrinsically cover the complementary quasi-steady state maser and transient superradiance regimes. We find that the variations in flaring time-scales measured for the different species/transitions, and sometimes even for a single spectral line, are manifestations of and are best modelled with Dicke’s superradiance, which naturally accounts for a modulation in the duration of flares through corresponding changes in the inversion pump. In particular, it can explain the peculiar behaviour observed for some features, such as the previously published result for the OH 1667 MHz transition at vlsr = +1.7 km s−1 as well as the methanol 6.7 GHz line at vlsr = −1.8 km s−1, through a partial quenching of the population inversion during flaring events.
Inhibition of nonsense-mediated mRNA decay reduces the tumorigenicity of human fibrosarcoma cells
Authors: Nasif Sofia , Colombo Martino , Uldry Anne-Christine , Schröder Markus S , de Brot Simone , Mühlemann Oliver
Published: September 2023

Nonsense-mediated mRNA decay (NMD) is a eukaryotic RNA decay pathway with roles in cellular stress responses, differentiation, and viral defense. It functions in both quality control and post-transcriptional regulation of gene expression. NMD has also emerged as a modulator of cancer progression, although available evidence supports both a tumor suppressor and a pro-tumorigenic role, depending on the model. To further investigate the role of NMD in cancer, we knocked out the NMD factor SMG7 in the HT1080 human fibrosarcoma cell line, resulting in suppression of NMD function. We then compared the oncogenic properties of the parental cell line, the SMG7-knockout, and a rescue cell line in which we re-introduced both isoforms of SMG7. We also tested the effect of a drug inhibiting the NMD factor SMG1 to distinguish NMD-dependent effects from putative NMD-independent functions of SMG7. Using cell-based assays and a mouse xenograft tumor model, we showed that suppression of NMD function severely compromises the oncogenic phenotype. Molecular pathway analysis revealed that NMD suppression strongly reduces matrix metalloprotease 9 (MMP9) expression and that MMP9 re-expression partially rescues the oncogenic phenotype. Since MMP9 promotes cancer cell migration and invasion, metastasis and angiogenesis, its downregulation may contribute to the reduced tumorigenicity of NMD-suppressed cells. Collectively, our results highlight the potential value of NMD inhibition as a therapeutic approach.
Trajectory of fecal lactoferrin for predicting prognosis in ulcerative colitis
Authors: Chen Rirong , Li Li , Tie Yizhe , Chen Minhu , Zhang Shenghong
Published: September 2023

Objectives

To investigate the characteristics and prognostic value of fecal lactoferrin trajectories in ulcerative colitis (UC).

Methods

This study used data from the UNIFI trial (ClinicalTrials.gov, NCT02407236) and included patients who received ustekinumab during induction for trajectory modeling (n = 637). Patients who received ustekinumab during maintenance therapy were used for 1-year outcome analyses (n = 403). The levels of fecal lactoferrin, fecal calprotectin, and serum C-reactive protein were measured at weeks 0, 2, 4, and 8. The trajectories of these biomarkers were developed using a latent class growth mixed model.

Results

The trajectories of fecal lactoferrin, fecal calprotectin, and serum C-reactive protein were distinct, but all were associated with prior exposure to anti-tumor necrosis factor agents and vedolizumab. Furthermore, the fecal lactoferrin trajectory was the most valuable predictor of endoscopic, clinical, and histological remission. Compared to the high/moderate-rapid decrease trajectory group, the moderate-slow decrease, high-slow decrease, and high-stable groups had adjusted odds ratios (95% confidence interval) of 0.38 (0.18, 0.78; P = 0.010), 0.47 (0.23, 0.93; P = 0.032), and 0.33 (0.17, 0.63; P = 0.001), respectively, of 1-year endoscopic remission. Patients with high/moderate-rapid decrease trajectories also had the highest likelihood of achieving clinical and histological remission. Finally, we developed a patient-stratification scheme based on fecal lactoferrin trajectories and concentrations. Patients with good, moderate, and poor prognoses in the scheme had a distinct probability of achieving 1-year endoscopic remission (52.7%, 30.9%, and 12.8%, respectively).

Conclusions

The trajectory of fecal lactoferrin is a valuable prognostic factor for 1-year remission in UC.
Viscoelasticity enhances collective motion of bacteria
Authors: Liao Wentian , Aranson Igor S
Published: September 2023

Bacteria form human and animal microbiota. They are the leading causes of many infections and constitute an important class of active matter. Concentrated bacterial suspensions exhibit large-scale turbulent-like locomotion and swarming. While the collective behavior of bacteria in Newtonian fluids is relatively well understood, many fundamental questions remain open for complex fluids. Here, we report on the collective bacterial motion in a representative biological non-Newtonian viscoelastic environment exemplified by mucus. Experiments are performed with synthetic porcine gastric mucus, natural cow cervical mucus, and a Newtonian-like polymer solution. We have found that an increase in mucin concentration and, correspondingly, an increase in the suspension’s elasticity monotonously increases the length scale of collective bacterial locomotion. On the contrary, this length remains practically unchanged in Newtonian polymer solution in a wide range of concentrations. The experimental observations are supported by computational modeling. Our results provide insight into how viscoelasticity affects the spatiotemporal organization of bacterial active matter. They also expand our understanding of bacterial colonization of mucosal surfaces and the onset of antibiotic resistance due to swarming.
Evidence on treat to target strategies in polymyalgia rheumatica and giant cell arteritis: a systematic literature review
Authors: Hysa Elvis , Bond Milena , Ehlers Lisa , Camellino Dario , Falzon Louise , Dejaco Christian , Buttgereit Frank , Aletaha Daniel , Kerschbaumer Andreas
Published: September 2023

Objectives

To inform an international task force about current evidence on Treat to Target (T2T) strategies in PMR and GCA.

Methods

A systematic literature research (SLR) was conducted in Medline, EMBASE, Cochrane Library, clinicaltrials.gov from their inception date to May 2022, and in the EULAR/ACR abstract database (2019–2021). Randomised clinical trials (RCTs) and non-randomised interventional studies published in English and answering at least one of the eleven PICO questions on T2T strategies, treatment targets and outcomes, framed by the taskforce, were identified. Study selection process, data extraction and risk of bias assessment were conducted independently by two investigators.

Results

Of 7809 screened abstracts, 397 were selected for detailed review and 76 manuscripts were finally included (31 RCTs, eight subgroup/exploratory analyses of RCTs and 37 non-randomised interventional studies). No study comparing a T2T strategy against standard of care was identified. In PMR RCTs, the most frequently applied outcomes concerned treatment (90.9% of RCTs), particularly the cumulative glucocorticoids (GC) dose and GC tapering, followed by clinical, laboratory and safety outcomes (63.3% each). Conversely, the most commonly reported outcomes in RCTs in GCA were prevention of relapses (72.2%), remission as well as treatment-related and safety outcomes (67.0% each).

Conclusions

This SLR provides evidence and highlights the knowledge gaps on T2T strategies in PMR and GCA, informing the task force developing T2T recommendations for these diseases.
Role of oral phytogenic supplementation to protect cardiac, hepatic, nephrotic, and splenic oxidative stress in broiler chickens
Authors: Abubakar Jimoh Olatunji , Uchechi Nwachukwu Chinwe , Olayinka Abosede Ojo , Oladimeji Samuel Tughobo
Published: September 2023

This study investigated the effects of adding essential oils of garlic, ginger, turmeric, and cinnamon to drinking water on cardiac, hepatic, nephrotic, and splenic oxidative status of broiler chickens. A batch of 200 1-d old Arbo acre broiler chicks was administered with Control (Water: no additive), 30 ml/L of cinnamon, ginger, turmeric, or garlic essential oils in drinking water for 42 d. On day 43, three broiler chickens/replicates were sampled randomly, sacrificed, and eviscerated. The hearts, spleens, kidneys, and livers were excised and assayed for glutathione peroxidase, total antioxidant activity, catalase, superoxide dismutase, and lipid peroxidation using standard protocols. In spleen broiler chickens, all additive essential oils increased (P < 0.05) total antioxidant activity. Catalase, superoxide dismutase, and glutathione peroxidase significantly increased (P < 0.05) in garlic, ginger, and turmeric essential oils except cinnamon. In kidney broiler chickens, lipid peroxidation was significantly reduced (P < 0.05) in all the additive essential oils. Garlic, cinnamon, and ginger essential oils increased (P < 0.05) catalase, superoxide dismutase, and glutathione peroxidase in kidney broiler chickens. In liver broiler chickens, lipid peroxidation, and glutathione peroxidase were higher (P < 0.05) in cinnamon essential oil than other additive essential oils. Superoxide dismutase and catalase were higher (P < 0.05) in turmeric essential oils. In heart broiler chickens, all the additive essential oils significantly decreased (P < 0.05) lipid peroxidation and increased (P < 0.05) total antioxidant activity. In conclusion, oral garlic, turmeric, and ginger essential oils supplementation did not reduce lipid peroxidation in spleen, whereas cinnamon essential oil caused lipid peroxidation in liver of broiler chickens.
Targeting Pharmacotherapies for Inflammatory and Cardiorenal Endpoints in Kidney Disease
Authors: Huck Daniel M. , Buckley Leo F. , Chandraker Anil , Blankstein Ron , Weber Brittany
Published: September 2023

Inflammation is an important contributor to excess cardiovascular risk and progressive renal injury in people with chronic kidney disease (CKD). Dysregulation of the innate and adaptive immune system is accelerated by CKD and results in increased systemic inflammation, a heightened local vascular inflammatory response leading to accelerated atherosclerosis, and dysfunction of the cardiac and renal endothelium and microcirculation. Understanding and addressing the dysregulated immune system is a promising approach to modifying cardiorenal outcomes in people with CKD. However, targeted pharmacotherapies adopted from trials of non-CKD and cardiorheumatology populations are only beginning to be developed and tested in human clinical trials. Pharmacotherapies that inhibit the activation of the NOD-like receptor protein 3 inflammasome and the downstream cytokines interleukin-1 and interleukin-6 are the most well-studied. However, most of the available evidence for efficacy is from small clinical trials with inflammatory and cardiorenal biomarker endpoints, rather than cardiovascular event endpoints, or from small CKD subgroups in larger clinical trials. Other pharmacotherapies that have proven beneficial for cardiorenal endpoints in people with CKD have been found to have pleiotropic anti-inflammatory benefits including statins, mineralocorticoid receptor antagonists, sodium-glucose cotransporter 2 inhibitors, and glucagon-like peptide-1 agonists. Finally, emerging therapies in CKD such as interleukin-6 inhibition, small-interfering RNA against lipoproteins, aryl hydrocarbon receptor inhibitors, and therapies adopted from the renal transplant population including mammalian target of rapamycin inhibitors and T regulatory cell promoters may have benefits for cardiorenal and inflammatory endpoints but require further investigation in clinical trials.
Will ChatGPT3 Substitute for us as Clozapine Experts?
Authors: de Leon Jose , De Las Cuevas Carlos
Published: September 2023

Background

ChatGPT3 is a new artificial intelligence program released on February 13, 2023.

Method

The authors tested ChatGPT3 on February 18, 2023, and repeated the test a week later. They used their expertise on the effects of ethnic ancestry in the stratification of clozapine dosing and the new idea that they published in March 2022 that African-Americans need higher clozapine doses because they have higher clozapine clearance.

Results

In the first interaction on February 18, ChatGPT3 provided reasonable and very up-to-date information, which included a comment that patients of African ancestry have higher clozapine metabolism. The other 4 interactions became progressively more concerning as we asked ChatGPT3 to provide references to justify the latter statement. ChatGPT3 provided non-existent “references” using articles from real journals, with real authors, false PubMed identifiers, and false titles. Moreover, ChatGPT3 said that the first author wrote in 2003 that African-Americans had higher CYP1A2 activity when that did not happen until 2022. One week later, the second author repeated the same set of questions. This time ChatGPT3 described the opposite, that African-Americans have “lower” CYP1A2 activity and “slower” metabolism. ChatGPT3 provided another set of articles to justify the information; some were real but did not comment on clozapine metabolism in African-Americans while others did not exist.

Conclusions

ChatGPT3 provided a mixture of truth, twisted reality, and non-existent “facts.” Within one week it defended opposite positions regarding a clinically relevant issue such as using higher or lower clozapine doses in African-Americans.
Pathophysiology updates: gastroduodenal injury and repair mechanisms
Authors: Hagen Susan J.
Published: September 2023

Purpose of review

Although the mucosal barrier serves as a primary interface between the environment and host, little is known about the repair of acute, superficial lesions or deeper, persistent lesions that if not healed, can be the site of increased permeability to luminal antigens, inflammation, and/or neoplasia development.

Recent findings

Recent studies on acute superficial lesions have focused on calcium signaling and focal adhesion kinase, which regulate cell migration and controlled matrix adhesion during restitution. Microfluidic organ-on-a-chip and gut-on-a-chip models continued in development to support reductionist studies of epithelial-bacterial and/or epithelial-immune cell interactions during mucosal barrier disruption. In fact, these models may allow personalized medicine studies in the future using patient-derived cells to evaluate injury and repair mechanisms. Work done in the past year evaluated the safety and efficacy of acid blocking drugs on ulcer healing, with new animal studies providing evidence that each drug affects the microbiome in a different way that can be correlated with its efficacy in ulcer healing. Lastly, work to understand the way in which mature epithelial cells or committed stem cells dedifferentiate, reprogram, proliferate, and then regenerate the gastroduodenal mucosa after injury was a major focus of studies in the past year.

Recent studies highlight novel mechanisms that promote restitution and mucosal regeneration after injury of the gastroduodenal mucosa.
Step on the accelerator: modern treatment of constipation
Authors: Staursky Daniel , Shimoga Dhanush , Sharma Amol
Published: September 2023

Purpose of review

This review aims to explore effective management of constipation, examine challenges in making a positive diagnosis, and highlights the significance of a positive patient-provider relationship and emerging treatments.

Recent findings

Less than one-fifth of patients feel satisfied with treatment of their constipation. Sixty percent of patients with functional dyspepsia and gastroparesis have severe to very severe constipation that correlates with their upper gastrointestinal symptom severity. Two gold kiwifruits are noninferior to 10 g of psyllium in the treatment of constipation. More than 40% of patients undergoing lumbar fusion continue to fill opioid prescriptions 90 days after surgery, contributing to 80 000 chronic opioid users annually. Most patients are using over-the-counter (OTC) treatments for constipation with greater than 60% dissatisfied. Pharmacologic management involves the use of GCC agonists and emerging drug classes such as bile acid transport inhibitors and sodium hydrogen exchanger isoform 3 (NHE3) inhibitors. Nonpharmacologic treatments, including neuromodulation and FDA-approved vibrating capsule, show promise in improving symptoms and quality of life.

Constipation significantly impacts patients’ quality of life and well being and the majority of patients are refractory to conservative measures and OTC treatments. Both pharmacologic and nonpharmacologic treatments hold promise for improving constipation and quality of life.
Recombinant anti-human epidermal growth factor receptor type 2 single-chain variable fragment-alpha-luffin fusion protein as a putative immunotoxin against human epidermal growth factor receptor type 2-positive breast cancer cells: an experimental research
Authors: Damough Shadi , Bayat Elham , Oghabi Bakhshaiesh Tayebeh , Barkhordari Farzaneh , Esmaeili Rezvan , Nematollahi Leila , Talebkhan Yeganeh
Published: September 2023

Background:

Breast cancer is one of the most frequent causes of cancer death in women. The application of immunotoxins to target overexpressed biomarkers on the surface of cancer cells and delivery of the toxin molecules into these cells has attracted too much attention during the last decade.

Objectives:

This study was conducted to investigate the possible in-vitro cytotoxic and apoptotic activity of previously designed recombinant immunotoxin compromising anti-HER2 single-chain variable fragment (scFv) and alpha-luffin protein in human epidermal growth factor receptor type 2 (HER2)-positive and HER2-negative breast cancer cell lines.

Materials and methods:

The previously designed recombinant immunotoxin and alpha-luffin protein were expressed inE. colihost cells and purified using Ni-affinity chromatography. The cytotoxicity of the proteins was tested through MTT and apoptosis studies on HER2-positive and HER2-negative breast cancer cell lines.

Results:

Treatment of SKBR3 and MDA-MB-468 cells with the immunotoxin caused differential cytotoxicity and apoptotic events. Flow cytometry analysis indicated that the immunotoxin could arrest SKBR3 cells at the G0/G1 phase and induce apoptosis and cell death which were not observed in HER2-negative MDA-MB-468 cells. Annexin V/PI staining revealed late apoptotic events in SKBR3 cells treated with the immunotoxin which was different from the early apoptosis induced by the alpha-luffin protein alone.

Conclusions:

This immunotoxin could be a promising tool in developing new targeted therapeutic agents against HER2-positive cancer cells. Animal experiments are needed before making firmed conclusions.
Preexisting anticoagulation is an independent predictor of mortality in geriatric trauma patients – a retrospective cohort study
Authors: Patel Nikhil , Kania Thomas , Demissie Seleshi , Le Timothy , Fusco Peter , Yoon Justin , Lee Bryan , Doran Joseph , Liu Jacqueline , Singer Tori , Glinik Galina , Azab Basem , Haney Olivia , Esposito Christopher , Mukherjee Indraneil , Atanassov Krassimir , Khodorkovsky Boris , Younan Duraid
Published: September 2023

Introduction:

Preexisting anticoagulation is common among geriatric trauma patients. Geriatric trauma patients have a higher risk of mortality compared to younger patients. We sought to evaluate the association of preexisting anticoagulation with mortality in a group of geriatric trauma patients.

Methods:

A retrospective review of geriatric trauma patients was conducted for those admitted to a Level 1 trauma center from January 2018 to December 2020. Vital signs, demographics, injury characteristics, laboratory data, and mortality were all collected. Multivariable logistic regression analysis was performed for the association of preexisting anticoagulation and a primary endpoint of all-cause mortality. These groups were controlled for preexisting comorbidities, injury severity scores, and systolic blood pressure in the emergency department.

Results:

Four thousand four hundred thirty-two geriatric patients were admitted during the study period. This cohort was made up of 36.9% men and 63.1% women. Three thousand eight hundred fifty-nine (87.2%) were white; the average age was 81±8.5 years, and the median injury severity score (ISS) was 5. The mean systolic blood pressure was 150±32 mmHg, mean heart rate was 81±16 bpm, mean lactate was 2.3±1.3, mean hematocrit was 37.3±8.8, and mean international normalized ratio (INR) was 1.7±10.3. One thousand five hundred ninety-two (35.9%) patients were on anticoagulation (AC) upon presentation. One hundred and sixty-five (3.7%) mortalities were recorded. Multivariable logistic regression analysis results show that preexisting anticoagulation [ odds ratio (OR) 1.92, 95% CI 1.36–2.72] was independently predictive of death. The analysis was adjusted for systolic BP in the emergency department less than90 mmHg (OR 5.55, 95% CI 2.83–10.9), having more than 1 comorbidity (OR 2.30, 95% CI 1.57–3.38) and ISS (OR 1.13, 95% CI 1.10–1.15).

Conclusion:

Our study indicates that preexisting anticoagulation is associated with mortality among geriatric trauma patients.
Neptune versus canister-based surgical waste management in Europe: results of the GREEN study
Authors: Baker Sarah , Clark Julie , Pla Angels B. , Feixas Eulalia V. , Huegel Julianne , Tariq Luqman
Published: September 2023

Background:

Ineffective surgical fluid waste management in operating rooms (OR) creates a significant environmental burden, reduces OR efficiency, and adds physical challenges for surgical staff. There is a need for waste management systems that improve OR efficiency, safety, and sustainability. The GREEN study (Greening operating Rooms in EuropE comparing Neptune vs. canisters) was conducted to compare the impact of two fluid waste management systems.

Materials and methods:

This 2-arm, nonrandomized, prospective service evaluation of fluid waste extraction was conducted using observational time series and surveys. Fluid waste-related data were collected from routine urologic and orthopedic surgeries across three European hospital sites. The primary endpoint of waste disposal impact was the volume of treated waste after surgery (kilograms) using Stryker’s Neptune device (n=43) or canisters (n=41). The authors hypothesized that the surgical waste volume related to Neptune is less than the waste volume related to canisters. Secondary endpoints included time efficiency, user satisfaction, and staff ergonomics.

Results:

The total weight of device-related treated waste products was reduced by 98.5% when using Neptune (0.2±0.7 kg) compared with traditional canisters (13.2±16.6 kg;P<0.001). Decreased waste weight also translated to enhanced ergonomic safety for surgical staff, as Neptune reduced surgical fluid weight handled by staff by an average of 34 kg per procedure, a 96% reduction compared to canisters. Furthermore, the use of the Neptune system improved OR efficiency by reducing the number of staff required to manage the fluid suction device (P<0.001) and the time spent disposing of fluid waste (P<0.001).

Conclusion:

Stryker’s Neptune waste management system significantly reduces the volume of treated waste per surgery and improves OR efficiency, staff safety, and user satisfaction over the traditional canister system. This is a more eco-responsible approach to OR fluid waste management and could be considered in any healthcare establishment that generates fluid waste.
Vitamin D status and blood group among severe COVID-19 patients
Authors: Aryafar Mohamad , Gholami Farshid , Bozorgmehr Rama
Published: September 2023

Objective:

Prognosis of COVID-19 infection has been indicated to be associated with vitamin D status and ABO blood group. However, owing to discrepancies and an increased number of cases globally, the findings remain unclear. This study aimed to evaluate the association between vitamin D and ABO blood group systems in patients with severe COVID-19.

Methods:

In this cross-sectional study, COVID-19 patients referred to two hospitals in the capital of Iran, Tehran, admitted to the ICU ward due to the severity of COVID-19 were evaluated. Serum vitamin D and ABO levels were evaluated in these patients. The data obtained were statistically analyzed using SPSSv24.

Results:

Of 305 patients, 33.1% patients had O+ blood type, 27.8% had A+ blood type and 22.4% had B+ blood type. Vitamin D deficiency was significantly associated with a mortality rate among these patients, P<0.05. The blood group of the patients was not correlated with mortality. Thirty-seven percent of the patients in the study died because of COVID-19.

Conclusion:

In our study population, mortality due to COVID-19 was significantly associated with vitamin D deficiency but not the ABO blood group. We recommend further studies in this regard that include more variable and detailed biochemical analysis.
Omental torsion: diagnostic challenge in patients with sclerosing cholangitis and inflammatory bowel disease – case report
Authors: Malik Neha , Chorosho Saziini H. , Kumari Pratima , Kaur Rupinder , Singh Ravinder , Chopra Hitesh , Bin Emran Talha
Published: September 2023

Introduction and importance:

The omentum appears as an apron-like extension of the peritoneum.

Case presentation:

A 30-year-old male patient, presented to the emergency department with the chief complaints of acute nonradiating pain localized in the right-side abdomen for the past 3 days. The patient had a past medical history of sclerosing cholangitis (SC) with inflammatory bowel disease (IBD). The patient reported the pain as persistent, pressure-like, and moderate. The patient also had a low-grade fever and nausea at the time of admission. On examination, the vital signs were found as normal. The patient reported that the abdominal pain gets exacerbated after the meals, and increase in physical activity and movement. Due to the patient’s complaints and history of SC and IBD, these were considered as the possible diagnosis. After the diagnostic procedures, the patient was finally diagnosed with OT.

Clinical discussion:

This report presents a case of a patient suffering from omental torsion having history of SC and IBD. During the laparoscopic procedure, the diagnosis of omental torsion was confirmed. To our knowledge, no case report of omental torsion with IBD and SC is published in the literature.

Conclusion:

This seems to be a major diagnostic challenge as patients with IBD almost resembles the same clinical signs and symptoms as in the omental torsion. The possibility of misdiagnosis and delayed diagnosis could result in the unfavorable outcome. Therefore, the healthcare fraternities are advised to include the rare diseases such as OT as the differential diagnosis.
Osteolytic bone lesions as an initial presenting manifestation of adult acute lymphoblastic leukemia: a mini review
Authors: Al-Mashdali Abdulrahman F. , Al-Dubai Hussam N. , Yassin Mohamed A.
Published: September 2023

Hematological malignancies can lead to bone lesions, and the most common example is the osteolytic lesions found in multiple myeloma. Cases of osteolytic lesions have been rarely reported in acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma, Waldenström macroglobulinemia, chronic lymphocytic leukemia, acute myeloid leukemia, and myeloproliferative neoplasms. This review sheds light on the association between ALL and osteolytic bone lesions. To our knowledge, we found 15 cases of patients with ALL who developed osteolytic lesions. Most patients were males with a median age of 29 years. B-cell ALL was the most common type of ALL associated with osteolytic lesions. All patients presented with bone pain, and hypercalcemia was found in 80% of the reported cases. Osteolytic lesions were detected by plain radiography (X-ray) in approximately half of the patients; computed tomography, MRI, or PET scans confirmed the osteolytic lesions in the remaining patients. The axial skeleton was mainly affected. Based on our review, there was no association between osteolytic bone lesions and the Philadelphia chromosome. There are no case of spinal cord compression in adults ALL patients attributed to osteolytic lesions of the vertebra. The majority of patients received chemotherapy, and the outcomes among these patients were variable. Almost all of them achieved complete remission. However, two patients developed a disease relapse. Given that our review is solely based on case reports, we could not conclude if the presence of osteolytic bone lesions is a prognostic factor for adverse outcomes or indicates an ‘aggressive’ form of ALL.
Impact of independent multidisciplinary work on the survival rate of stage 3 and 4 nasopharyngeal cancer in Indonesia: a retrospective cohort study
Authors: Rizky Daniel , Yunarvika Vina , Putra Yasjudan R. , Pangarsa Eko A. , Kartiyani Ika , Panunggal Damianus G. , Hutajulu Susanna H. , Setiawan Budi , Hariadi Kartika W.T. , Santosa Damai , Herdini Camelia , Yoshuantari Naomi , Dhamiyati Wigati , Purwanto Ibnu
Published: September 2023

Background:

The utilization of a multidisciplinary team (MDT) strategy is a beneficial approach in integrating the knowledge and proficiencies of various fields to produce thorough and advantageous cancer treatment plans for patients. Nevertheless, MDT has yet to be widely adopted in Indonesia. In this study, the authors examined an early form of MDT in Indonesia that does not involve dedicated meetings, referred as independent multidisciplinary work (IMW). The objective is to investigate the differences in survival rates of nasopharyngeal cancer (NPC) patients who underwent treatment with and without IMW.

Materials and methods:

This study has a retrospective cohort design. Data were collected from the medical records of newly diagnosed stage 3 and 4 NPC patients between 2016 and 2018. The subjects were divided into two groups: the IMW group and the non-IMW group. The primary end point of the study is overall survival rate between the two groups. Kaplan–Meier survival analysis, log-rank test, and cox proportional hazard analysis were used for statistical analysis.

Results:

This study included a total of 124 patients with NPC, 81 patients in the IMW group and 43 patients in the non-IMW group. At the end of the 36-month follow-up period, the median survival of the IMW group was not reached, while in the non-IMW, it was 12 months [95% confidence intervals (95% CI), 8.78–15.22], hazard ratio (HR): 0.47 (95% CI, 0.28–0.78; P<0.01). The 1-year survival rate was 66.7% in the IMW group versus 46.5% in the non-IMW group (HR=0.7, 95% CI 0.49–0.99; P=0.03); the 2-year survival rate was 40.7% in the IMW group versus 16.3% in the non-IMW group (HR=0.4, 95% CI 0.19–0.83; P<0.01). Daniel Rizky, Vina Yunarvika, and Yasjudan Rastrama Putra, these authors contributed equally to this work. In the multivariate analysis, the IMW approach, ECOG (The Eastern Cooperative Oncology Group) status, distant metastasis, and treatment approach were significantly associated with survival outcome.

Conclusion:

The use of IMW approach in the treatment of NPC was associated with a better survival outcome compared to non-IMW treatment.
A rare case of malignant granular cell tumor of the cheek in a 16-year-old child: a case report
Authors: Saleh Mohanad , Sarahneh Husein Ahmad , Hroub Sara Ibrahim , Diab Laila khader , Elatawneh Taha mohammad , Wredat Saida Basem , Abubaker Amal Nasr
Published: September 2023

Introduction and importance:

Granular cell tumors (GCTs) are uncommon soft tissue tumors, predominantly benign lesions. Approximately 50% occur in the tongue, with a peak incidence in the fifth and sixth decades of life. However, in this case, a rare presentation of GCTs on the cheek of a 16-year-old young female, including a review of the literature.

Methods:

The medical records and histopathological slides of the case were retrospectively reviewed. This work has been reported based on Surgical CAse REport (SCARE) criteria.

Case presentation:

A 16-year-old female presented with a non-painful exophytic and pigmented cheek lesion that is rapidly growing. A primary concern was expressed as cosmetic in nature, a biopsy of the mass was taken, and histopathological findings showed a malignant tumor, mostly consistent with GCTs. She was recommended to have a total excision of the mass. During follow-up, facial MRI findings indicate granulation tissue versus recurrent/residual tumor at the site of surgery, without any evidence of cancer metastasis or spread.

Clinical discussion:

GCT is a tumor of Schwann cells, which is mostly benign with a 2% risk of malignant transformation. The peak incidence of this tumor is around the age of 50, and it is uncommon in young individuals. Clinically, GCT presents as a single, asymptomatic dermal or subcutaneous, brown-red nodule or papule, which grows slowly with diameter ranging from 0.5 to 3 cm. The definitive treatment for both benign and malignant GCTs is sufficient local excision with safe margins.

Conclusion:

GCT is an extremely rare tumor, with a peak incidence of fifth and sixth decay of age, which usually appear in the tongue (50% of cases); however, in this case, we present a 16-year-old female with a cheek mass diagnosed as GCT. In short, we think that GCT should be considered as one of the differential diagnoses of solitary facial masses at young ages.
Delayed presentation of traumatic diaphragmatic hernia complicated by bowel obstruction and perforation: a case report
Authors: Yadav Krishna Kumar , Ghimire Ranjeet , Rauniyar Ranjit , Khadka Rebanta , Lamsal Arun Batsa , Khadka Laxman , Yadav Rupesh Kumar , Yadav Pratibha
Published: September 2023

Post-traumatic diaphragmatic hernia is a rare but life-threatening condition resulting from a traumatic injury to the diaphragm. We present a case of a 48-year-old man with a history of fall injury and a delayed presentation of a right-sided diaphragmatic hernia with subsequent bowel obstruction and perforation in a patient with a history of trauma and tuberculosis. The patient underwent exploratory laparotomy with manual reduction of the herniated bowel, primary repair of the diaphragmatic defect, and the creation of a double-barrel ileostomy. This case highlights the importance of considering traumatic diaphragmatic hernia in patients with a history of trauma presenting with abdominal symptoms. Timely diagnosis and surgical intervention are crucial in preventing serious complications associated with this condition.