bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Preoperative Intravenous and Inhalational Dexmedetomidine on the Hemodynamic Response of Laryngoscopy: A Prospective Double-blinded Randomized Study
Authors: Singh Shivanya , Gupta Priyanka , Dhar Mridul , Pasha Arhan
Published: August 2024

ABSTRACT

Objective:

Laryngoscopy induces potent noxious stimuli causing reflex autonomic activation manifested by an increase in blood pressure and heart rate (HR). Various drugs with different routes have been tried to prevent this response. The literature comparing inhalational dexmedetomidine with intravenous (IV) dexmedetomidine to prevent laryngoscopy response is limited.

Methods:

A total of 150 American Society of Anesthesiologists Physical Status Class I/II, undergoing elective surgery requiring laryngoscopy and intubation, were included and randomized into two groups. Patients in Group DINH received nebulized dexmedetomidine (1 μg/kg) and in Group DIV received IV dexmedetomidine (0.5 μg/kg), 15 min before anesthesia induction. For blinding, nebulized or IV saline was used simultaneously. The primary outcome was to compare the mean arterial pressure (MAP) and HR at laryngoscopy, intubation, and 1, 5, and 10 min after intubation. The secondary outcome was to compare sedation, following the administration of dexmedetomidine, propofol consumption during induction, and any side effects.

Findings:

There was no significant difference in MAP (mmHg) postlaryngoscopy and intubation (immediate after intubation 78.5 ± 11.3 vs. 82.3 ± 16.0, P = 0.093). The mean HR was clinically similar in both groups postlaryngoscopy and intubation (immediate after intubation, 80.9 ± 12.5 vs. 76.3 ± 10.9). Patients in the DIV group were more sedated than the DINH (Ramsay Sedation Scale 3–4 vs. 1–2, P < 0.001). Bradycardia was seen in eight patients of the DIV group only.

Conclusion:

Preoperative nebulized dexmedetomidine is as effective as and safer than IV dexmedetomidine in preventing laryngoscopic response among adults.
Efficacy of Licorice as Adjunctive Therapy in Critically Ill Patients with COVID-19: A Randomized, Placebo-Controlled, Double-Blind Clinical Trial
Authors: Alikiaie Babak , Shalamzari Seyed Mohammad Hosseinian , Soltani Rasool , Yegdaneh Afsaneh , Mousavi Sarah
Published: August 2024

ABSTRACT

Objective:

There is no definitive pharmacological strategy for COVID-19; thus, medicinal herbs can be an appropriate option for COVID-19 management. We investigated the efficacy of a D-reglis® tablet (root extract of licorice) as adjuvant therapy in critically ill patients with COVID-19 at intensive care units (ICUs) of Alzahra Teaching Hospital affiliated with Isfahan University of Medical Sciences, Isfahan, Iran.

Methods:

In the present double-blind, randomized, placebo-controlled clinical trial, critically ill cases with COVID-19 (n = 52) received a D-reglis® tablet (760 mg) or a placebo tablet for 5 days. The ICU stay length was the primary outcome. The secondary outcome included the changes in oxygen saturation, duration of mechanical ventilation, mortality rate, and Sequential Organ Failure Assessment (SOFA) Score during the study period.

Findings:

The ICU stay was significantly lower in the licorice group than in the placebo group (P = 0.015). No significant difference was detected between the groups regarding oxygen saturation, SOFA score, duration of mechanical ventilation, and mortality rate.

Conclusion:

The licorice tablet (D-reglis®) as an adjuvant treatment showed promising results regarding the ICU stay length in critically ill COVID-19 patients. However, further clinical trials with larger sample sizes, further duration of intervention, measurement of inflammatory markers, and further study about the molecular mechanism of the effect of licorice on COVID-19 should be done to obtain more conclusive findings.
Evaluation of the Antimicrobial Resistance Pattern of Nosocomial Infections in Patients Hospitalized in Chamran Heart Educational, Medical, and Research Center of Isfahan
Authors: Dianatkhah Mehrnoush , Davoodi Zeinab Sadat , Soltani Rasool , Shafiee Fatemeh , Hosseini Alireza
Published: August 2024

ABSTRACT

Objective:

According to the importance of evaluating the antimicrobial resistance pattern in the management of nosocomial infections (NIs), we decided to investigate the prevalence of antimicrobial resistance in Chamran Heart Hospital.

Methods:

This retrospective cross-sectional observational study was performed for 6 months from February to July 2022 at Shahid Chamran Hospital of Isfahan, Iran. All hospitalized patients with any NIs were eligible for the study. Clinical specimens were obtained from patients with NIs. All specimens underwent microbial culture, and if bacterial growth developed, differential tests were performed. Antibiotic susceptibility testing also was performed per the standards of Clinical and Laboratory Standards Institute, 2022.

Findings:

Out of 201 examined samples, urinary infection (34.83%), pneumonia (27.86%), and sepsis (13.43%) were reported to be the most prevalent infections. Among Gram-negatives (76.12%), Citrobacter spp. (26.37%), Escherichia coli (24.87%), and Klebsiella spp. (11.44%) were the most common pathogens. About 54.9% of Citrobacter spp., 33.3% of E. coli, and 45.45% of Klebsiella spp. were resistant to carbapenems. About 1.88% and 15% of Citrobacter spp. were identified as pan-drug-resistant bacteria and extensively drug-resistant (XDR), respectively. In addition, 4.34% of Klebsiella spp. were identified as XDR. Among Gram-positives (23.88%), Enterococcus spp. (8.95%) was identified as the most common pathogen, and the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) was 11.11% and 61.11%, respectively.

Conclusion:

In our study, carbapenem-resistant Enterobacteriaceae accounts for about 50% of all NIs. Moreover, despite the low prevalence of MRSA, VRE was reported to be high in our center when compared with other studies.
Multisystem inflammatory syndrome in children – A serious emerging syndrome
Authors: Nazareth Samantha Valeni , Tauro Preetham Philip
Published: August 2024

Objective:

The objective of the study was to determine the clinical features, treatment received, and outcomes of severely ill children with multisystem inflammatory syndrome in children (MIS-C).

Methods:

The study was a retrospective observation carried out at a pediatric intensive care unit in a tertiary care hospital. The baseline history, investigations, treatment received, and outcomes of the disease in 14 critically ill children, who were diagnosed with MIS-C, were surveyed from October 2020 to January 2022.

Results:

There were 14 children who were diagnosed with MIS-C. All children received intensive care treatment and 7 children received a combination of steroid therapy and intravenous immunoglobulin. Out of 14 children, 12 of them survived and 2 expired.

Conclusion:

For children who are diagnosed with MIS-C, the outcome was good if detected early and treated on time.
A case report of subdiaphragmatic right kidney as a positional variant of cephalad renal ectopia
Authors: Reddy Chandana A. , Balasundaram Suganitha , Kulkarni Vasudha
Published: August 2024

Renal ectopia refers to the abnormal position of the kidney outside the renal fossa. It may be in sacral, lumbar, thoracic, or subdiaphragmatic regions, of which the latter is extremely rare and may be associated with congenital abnormalities. High renal ectopia is a rare disease that affects 1 in every 22 ectopic kidney occurrences. During the routine cadaveric dissection of a 50-year-old male, we observed an uncommon case of high ascent of the right kidney, up to the bare area of liver. The right kidney was normal in size and shape, and received a renal artery positioned obliquely, 3 mm below the origin of the left renal artery and its vein drained into the hepatic portion of the inferior venacava (IVC). Knowledge about the variations in the positions of the kidneys is very important as cephalad ectopic kidney may pose a challenge for surgical and interventional procedures.
Rosuvastatin-induced acute hepatitis: Insights from clinical experience on drug-induced liver injury
Authors: Poojary Bhavya , Jose Josmi , Nagpavan S R , Dhalayat Farahanaz Umarfaruk
Published: August 2024

In the field of cardiovascular health, rosuvastatin, a potent statin, holds significance as it aids in lowering cholesterol levels and mitigating the risk of cardiovascular diseases. While generally well tolerated, it is not without side effects. Common adverse reactions exist, and rare severe events such as liver injury and myopathy can occur. This case report sheds light on a specific incident involving a 49-year-old male patient who presented with a range of distressing symptoms, including loose motion, fever accompanied by chills, vomiting, nausea, abdominal pain, and disrupted sleep. Following an extensive investigation encompassing the patient’s medical history and laboratory tests, a diagnosis of drug-induced acute hepatitis was established, with rosuvastatin identified as the causative agent. Consequently, the statin therapy was promptly discontinued, and the patient was provided with symptomatic treatment until the liver-related investigations returned to normal. This case report underscores the paramount importance of diligent monitoring and surveillance in identifying and managing potential adverse effects associated with statin therapy, thereby safeguarding patient well-being and ensuring their safety.
Readiness and perceived barriers for self-directed learning among medical students and faculty members: An observational study
Authors: Gopalakrishnan Shivkumar , Vaithiyanathan P. , Elangovan Harikrishnan , Kandasamy Sangeetha , Ganesan Harissh
Published: August 2024

Background:

Self-directed learning (SDL) is an internationally accepted principle of adult education. CBME curriculum implemented by the Government of India has allotted 280 hours of SDL in all subjects for undergraduate medical students. SDL is yet to root into the student community as norms and a definitive program evaluation is still not in shape.

Aim and Objective:

To identify students’ readiness and perceived barriers towards SDL.

Materials and Methods:

This questionnaire-based study was conducted between January 2023 to May 2023 among faculties and students. The 12 items of self-directed learning readiness instrument were adopted from Shen et al.

Results:

A total of 480 MBBS students participated. 97.7% of students were aware of SDL in their first year. The highest score was in the “self-monitoring” domain (Mean ± SD = 3.89 ± 0.64) and the lowest score was in “Planning and Implementation” (3.56 ± 0.80). Students perceived that SDL would enhance their communication (50.41%), critical thinking (49.2%), problem solving (40.4%), research (39.8%) and cognitive skills (37.1%). Among barriers the most significant was lack of guidance and resource deficiency (30.4%, 29%). In this study 52 CISP completed faculty participated and 82.69% agreed students were ready for SDL. The suggested resource materials were reference books and online materials (90.38% & 26.92%).

Conclusion:

Medical students’ readiness for SDL is quite encouraging which was also attested by 83% of faculty. Given the fertile nidus of growing young minds if deficiencies are addressed, the medical curriculum would be fortified with SDL ensuring long term benefits.
Role of intraoperative entroscopy in obscure small bowel gastrointestinal bleed
Authors: Ganesh M. K. , Kanchodu Sudheer , Janardhan Sagar Nambiar , Rao H. T. Nagarjun
Published: August 2024

Obscure gastrointestinal bleed (OGIB) is defined as bleeding of unknown origin that persists or recurs after a negative initial or primary endoscopy (colonoscopy and upper gastrointestinal [GI] endoscopy) and imaging. Approximately 5% of all GI bleeding is obscure GI bleed. Abnormal blood vessels arteriovenous malformations (AVMs) cause 30%–40% of small intestinal bleeds. AVMs are the main source of bleeding in patients over the age of 50 years. Tumors (benign and malignant), polyps, Crohn’s disease, and ulcers are some of the other causes of bleeding. Various diagnostic modalities available to detect small intestinal bleed are upper GI endoscopy, colonoscopy, contrast-enhanced computed tomography scan of the abdomen with angiogram, small bowel enteroscopy, video capsule endoscopy, and scintigraphy studies. Advanced imaging/diagnostic modalities may not be available in all centers, posing a great challenge in the localization of the source of GI bleed. This series highlights the role of diagnostic laparoscopy with intraoperative enteroscope (IOE) in the management of OGIB.
Long noncoding RNA GAS5 acts as a competitive endogenous RNA to regulate GSK-3β and PTEN expression by sponging miR-23b-3p in Alzheimer’s disease
Authors: Zeng Li , Zhao Kaiyue , Liu Jianghong , Liu Mimin , Cai Zhongdi , Sun Ting , Li Zhuorong , Liu Rui
Published: August 2024

Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The long noncoding RNA growth arrest-specific 5 (GAS5) is a member of the 5'-terminal oligopyrimidine gene family that may be involved in neurological disorders, but its role in Alzheimer's disease remains unclear. This study aimed to investigate the function of GAS5 and construct a GAS5-associated competitive endogenous RNA network comprising potential targets. RNA sequencing results showed that GAS5 was upregulated in five familial Alzheimer's disease (5×FAD) mice, APPswe/PSEN1dE9 (APP/PS1) mice, Alzheimer's disease-related APPswe cells, and serum from patients with Alzheimer's disease. Functional experiments with targeted overexpression and silencing demonstrated that GAS5 played a role in cognitive dysfunction and multiple Alzheimer's disease-associated pathologies, including tau hyperphosphorylation, amyloid-beta accumulation, and neuronal apoptosis. Mechanistic studies indicated that GAS5 acted as an endogenous sponge by competing for microRNA-23b-3p (miR-23b-3p) binding to regulate its targets glycogen synthase kinase 3beta (GSK-3β) and phosphatase and tensin homologue deleted on chromosome 10 (PTEN) expression in an Argonaute 2-induced RNA silencing complex (RISC)-dependent manner. GAS5 inhibited miR-23b-3p-mediated GSK-3β and PTEN cascades with a feedforward PTEN/protein kinase B (Akt)/GSK-3β linkage. Furthermore, recovery of GAS5/miR-23b-3p/GSK-3β/PTEN pathways relieved Alzheimer's disease-like symptoms in vivo, indicated by the amelioration of spatial cognition, neuronal degeneration, amyloid-beta load, and tau phosphorylation. Together, these findings suggest that GAS5 promotes Alzheimer's disease pathogenesis. This study establishes the functional convergence of the GAS5/miR-23b-3p/GSK-3β/PTEN pathway on multiple pathologies, suggesting a candidate therapeutic target in Alzheimer's disease.
Decoding molecular mechanisms: brain aging and Alzheimer’s disease
Authors: Hayat Mahnoor , Syed Rafay Ali , Qaiser Hammad , Uzair Mohammad , Al-Regaiey Khalid , Khallaf Roaa , Albassam Lubna Abdullah Mohammed , Kaleem Imdad , Wang Xueyi , Wang Ran , Bhatti Mehwish S. , Bashir Shahid
Published: August 2024

The complex morphological, anatomical, physiological, and chemical mechanisms within the aging brain have been the hot topic of research for centuries. The aging process alters the brain structure that affects functions and cognitions, but the worsening of such processes contributes to the pathogenesis of neurodegenerative disorders, such as Alzheimer’s disease. Beyond these observable, mild morphological shifts, significant functional modifications in neurotransmission and neuronal activity critically influence the aging brain. Understanding these changes is important for maintaining cognitive health, especially given the increasing prevalence of age-related conditions that affect cognition. This review aims to explore the age-induced changes in brain plasticity and molecular processes, differentiating normal aging from the pathogenesis of Alzheimer’s disease, thereby providing insights into predicting the risk of dementia, particularly Alzheimer’s disease.
Modulation of the Nogo signaling pathway to overcome amyloid-β-mediated neurite inhibition in human pluripotent stem cell–derived neurites
Authors: Goncalves Kirsty , Przyborski Stefan
Published: August 2024

JOURNAL/nrgr/04.03/01300535-202509000-00026/figure1/v/2024-12-31T000210Z/r/image-tiff

Neuronal cell death and the loss of connectivity are two of the primary pathological mechanisms underlying Alzheimer’s disease. The accumulation of amyloid-β peptides, a key hallmark of Alzheimer’s disease, is believed to induce neuritic abnormalities, including reduced growth, extension, and abnormal growth cone morphology, all of which contribute to decreased connectivity. However, the precise cellular and molecular mechanisms governing this response remain unknown. In this study, we used an innovative approach to demonstrate the effect of amyloid-β on neurite dynamics in both two-dimensional and three-dimensional culture systems, in order to provide more physiologically relevant culture geometry. We utilized various methodologies, including the addition of exogenous amyloid-β peptides to the culture medium, growth substrate coating, and the utilization of human-induced pluripotent stem cell technology, to investigate the effect of endogenous amyloid-β secretion on neurite outgrowth, thus paving the way for potential future applications in personalized medicine. Additionally, we also explore the involvement of the Nogo signaling cascade in amyloid-β-induced neurite inhibition. We demonstrate that inhibition of downstream ROCK and RhoA components of the Nogo signaling pathway, achieved through modulation with Y-27632 (a ROCK inhibitor) and Ibuprofen (a Rho A inhibitor), respectively, can restore and even enhance neuronal connectivity in the presence of amyloid-β. In summary, this study not only presents a novel culture approach that offers insights into the biological process of neurite growth and inhibition, but also proposes a specific mechanism for reduced neural connectivity in the presence of amyloid-β peptides, along with potential intervention points to restore neurite growth. Thereby, we aim to establish a culture system that has the potential to serve as an assay for measuring preclinical, predictive outcomes of drugs and their ability to promote neurite outgrowth, both generally and in a patient-specific manner.
Contribution of ferroptosis and SLC7A11 to light-induced photoreceptor degeneration
Authors: Huang Xiaoxu , Zhang Yumeng , Jiang Yuxin , Li Tong , Yang Shiqi , Wang Yimin , Yu Bo , Zhou Minwen , Zhang Guanran , Zhao Xiaohuan , Sun Junran , Sun Xiaodong
Published: August 2024

Progressive photoreceptor cell death is one of the main pathological features of age-related macular degeneration and eventually leads to vision loss. Ferroptosis has been demonstrated to be associated with retinal degenerative diseases. However, the molecular mechanisms underlying ferroptosis and photoreceptor cell death in age-related macular degeneration remain largely unexplored. Bioinformatics and biochemical analyses in this study revealed xC-, solute carrier family 7 member 11-regulated ferroptosis as the predominant pathological process of photoreceptor cell degeneration in a light-induced dry age-related macular degeneration mouse model. This process involves the nuclear factor-erythroid factor 2-related factor 2-solute carrier family 7 member 11-glutathione peroxidase 4 signaling pathway, through which cystine depletion, iron ion accumulation, and enhanced lipid peroxidation ultimately lead to photoreceptor cell death and subsequent visual function impairment. We demonstrated that solute carrier family 7 member 11 overexpression blocked this process by inhibiting oxidative stress in vitro and in vivo. Conversely, solute carrier family 7 member 11 knockdown or the solute carrier family 7 member 11 inhibitor sulfasalazine and ferroptosis-inducing agent erastin aggravated H2O2-induced ferroptosis of 661W cells. These findings indicate solute carrier family 7 member 11 may be a potential therapeutic target for patients with retinal degenerative diseases including age-related macular degeneration.
Gamma-type immunoglobulin enhances phagocytosis of amyloid-beta fibrils by microglia
Authors: Zhou Tian , Zhong Yue , Yu Shoujun , Sun Ruibing , Zhang Zhenwei , Du Xiaoyan , Lee Simon Ming-Yuen , Chen Zhitong , Tian Weiming , Lai Yuxiao , Song Bing , Zheng Yiming , Xu Zhen
Published: August 2024

The peripheral immune system has emerged as a regulator of neurodegenerative diseases such as Alzheimer’s disease. Microglia are resident immune cells in the brain that may orchestrate communication between the central nervous system and peripheral immune system, though the mechanisms are unclear. Here, we found that gamma-type immunoglobulin, a product originating from peripheral blood B cells, localized in the brain parenchyma of multiple mouse models with amyloid pathology, and was enriched on microglia but not on other brain cell types. Further experiments showed that gamma-type immunoglobulin bound to microglial cell membranes and led to diverse transcriptomic changes, including upregulation of pathways related to phagocytosis and immunity. Functional assays demonstrated that gamma-type immunoglobulin enhanced microglial phagocytic capacity for amyloid-beta fibrils via its Fc, but not Fab, fragment. Our data indicate that microglia, when exposed to gamma-type immunoglobulin, exhibit an enhanced capacity for clearing amyloid-beta fibrils, potentially via the gamma-type immunoglobulin Fc fragment signaling pathway. This suggests that parenchymal gamma-type immunoglobulin should be further investigated to determine whether it may play a beneficial role against Alzheimer’s disease by enhancing microglial function.
Low-density lipoprotein receptor-related protein 1 mediates α-synuclein transmission from the striatum to the substantia nigra in animal models of Parkinson’s disease
Authors: Luo Hanjiang , Peng Caixia , Wu Chengli , Liu Chengwei , Li Qinghua , Yu Shun , Liu Jia , Chen Min
Published: August 2024

α-Synuclein accumulation and transmission are vital to the pathogenesis of Parkinson's disease, although the mechanisms underlying misfolded α-synuclein accumulation and propagation have not been conclusively determined. The expression of low-density lipoprotein receptor–related protein 1, which is abundantly expressed in neurons and considered to be a multifunctional endocytic receptor, is elevated in the neurons of patients with Parkinson's disease. However, whether there is a direct link between low-density lipoprotein receptor- related protein 1 and α-synuclein aggregation and propagation in Parkinson's disease remains unclear. Here, we established animal models of Parkinson's disease by inoculating monkeys and mice with α-synuclein pre-formed fibrils and observed elevated low-density lipoprotein receptor–related protein 1 levels in the striatum and substantia nigra, accompanied by dopaminergic neuron loss and increased α-synuclein levels. However, low-density lipoprotein receptor–related protein 1 knockdown efficiently rescued dopaminergic neurodegeneration and inhibited the increase in α-synuclein levels in the nigrostriatal system. In HEK293A cells overexpressing α-synuclein fragments, low-density lipoprotein receptor–related protein 1 levels were upregulated only when the N-terminus of α-synuclein was present, whereas an α-synuclein fragment lacking the N-terminus did not lead to low-density lipoprotein receptor–related protein 1 upregulation. Furthermore, the N-terminus of α-synuclein was found to be rich in lysine residues, and blocking lysine residues in PC12 cells treated with α-synuclein pre-formed fibrils effectively reduced the elevated low-density lipoprotein receptor–related protein 1 and α-synuclein levels. These findings indicate that low-density lipoprotein receptor–related protein 1 regulates pathological transmission of α-synuclein from the striatum to the substantia nigra in the nigrostriatal system via lysine residues in the α-synuclein N-terminus.
Neuroprotective potential for mitigating ischemia-reperfusion-induced damage
Authors: Ye Zi , Liu Runqing , Wang Hangxing , Zuo Aizhen , Jin Cen , Wang Nan , Sun Huiqi , Feng Luqian , Yang Hua
Published: August 2024

Reperfusion following cerebral ischemia causes both structural and functional damage to brain tissue and could aggravate a patient’s condition; this phenomenon is known as cerebral ischemia-reperfusion injury. Current studies have elucidated the neuroprotective role of the sirtuin protein family (Sirtuins) in modulating cerebral ischemia-reperfusion injury. However, the potential of utilizing it as a novel intervention target to influence the prognosis of cerebral ischemia-reperfusion injury requires additional exploration. In this review, the origin and research progress of Sirtuins are summarized, suggesting the involvement of Sirtuins in diverse mechanisms that affect cerebral ischemia-reperfusion injury, including inflammation, oxidative stress, blood–brain barrier damage, apoptosis, pyroptosis, and autophagy. The therapeutic avenues related to Sirtuins that may improve the prognosis of cerebral ischemia-reperfusion injury were also investigated by modulating Sirtuins expression and affecting representative pathways, such as nuclear factor-kappa B signaling, oxidative stress mediated by adenosine monophosphate-activated protein kinase, and the forkhead box O. This review also summarizes the potential of endogenous substances, such as RNA and hormones, drugs, dietary supplements, and emerging therapies that regulate Sirtuins expression. This review also reveals that regulating Sirtuins mitigates cerebral ischemia-reperfusion injury when combined with other risk factors. While Sirtuins show promise as a potential target for the treatment of cerebral ischemia-reperfusion injury, most recent studies are based on rodent models with circadian rhythms that are distinct from those of humans, potentially influencing the efficacy of Sirtuins-targeting drug therapies. Overall, this review provides new insights into the role of Sirtuins in the pathology and treatment of cerebral ischemia-reperfusion injury.
Neuronal regulated cell death in aging-related neurodegenerative diseases: key pathways and therapeutic potentials
Authors: Song Run , Yin Shiyi , Wu Jiannan , Yan Junqiang
Published: August 2024

Regulated cell death (such as apoptosis, necroptosis, pyroptosis, autophagy, cuproptosis, ferroptosis, disulfidptosis) involves complex signaling pathways and molecular effectors, and has been proven to be an important regulatory mechanism for regulating neuronal aging and death. However, excessive activation of regulated cell death may lead to the progression of aging-related diseases. This review summarizes recent advances in the understanding of seven forms of regulated cell death in age-related diseases. Notably, the newly identified ferroptosis and cuproptosis have been implicated in the risk of cognitive impairment and neurodegenerative diseases. These forms of cell death exacerbate disease progression by promoting inflammation, oxidative stress, and pathological protein aggregation. The review also provides an overview of key signaling pathways and crosstalk mechanisms among these regulated cell death forms, with a focus on ferroptosis, cuproptosis, and disulfidptosis. For instance, FDX1 directly induces cuproptosis by regulating copper ion valency and dihydrolipoamide S-acetyltransferase aggregation, while copper mediates glutathione peroxidase 4 degradation, enhancing ferroptosis sensitivity. Additionally, inhibiting the Xc- transport system to prevent ferroptosis can increase disulfide formation and shift the NADP+/NADPH ratio, transitioning ferroptosis to disulfidptosis. These insights help to uncover the potential connections among these novel regulated cell death forms and differentiate them from traditional regulated cell death mechanisms. In conclusion, identifying key targets and their crosstalk points among various regulated cell death pathways may aid in developing specific biomarkers to reverse the aging clock and treat age-related neurodegenerative conditions.
Bromodomain-containing protein 4 knockdown promotes neuronal ferroptosis in a mouse model of subarachnoid hemorrhage
Authors: Lu Peng , Zhang Fan , Yang Lei , He Yijing , Kong Xi , Guo Kecheng , Xie Yuke , Xie Huangfan , Xie Bingqing , Jiang Yong , Peng Jianhua
Published: August 2024

Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage. Neuronal ferroptosis in particular plays an important role in early brain injury. Bromodomain-containing protein 4, a member of the bromo and extraterminal domain family of proteins, participated in multiple cell death pathways, but the mechanisms by which it regulates ferroptosis remain unclear. The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro. Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons, and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo. In addition, ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage. Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis. Using cleavage under targets and tagmentation analysis, we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro. Furthermore, treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074, a Raf-1 inhibitor, exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway. Moreover, targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage. Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage, and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.
Convex co-compact groups with one-dimensional boundary faces
Authors: Islam Mitul , Zimmer Andrew
Published: August 2024

In this paper, we consider convex co-compact subgroups of the projective linear group. We prove that such a group is relatively hyperbolic with respect to a collection of virtually Abelian subgroups of rank 2 if and only if each open face in the ideal boundary has dimension at most one. We also introduce the “coarse Hilbert dimension” of a subset of a convex set and use it to characterize when a naive convex co-compact subgroup is word hyperbolic or relatively hyperbolic with respect to a collection of virtually Abelian subgroups of rank 2.
Quadratic algebras associated with exterior 3-forms
Authors: Dubois-Violette Michel , Torrecillas Blas
Published: August 2024

This paper is devoted to the study of the quadratic algebras with relations generated by superpotentials which are exterior 3-forms. Such an algebra is regular if and only if it is Koszul and is then a 3-Calabi–Yau domain. After some general results, we investigate the case of the algebras generated in low dimensions

n

with

n\leq 7

. We show that whenever the ground field is algebraically closed, all these algebras associated with 3-regular exterior 3-forms are regular and are thus 3-Calabi–Yau domains. This result does not generalize to dimensions

n

with

n\geq 8

: we describe a counterexample in dimension

n=8

.
Pulse Oximetry Accuracy in Children with Dark Skin Tones: Relevance to Acute Lower Respiratory Infection Care in Low- and Middle-Income Countries
Authors: Hooli Shubhada , Colbourn Tim , Shah Manish I. , Murray Kristy , Mandalakas Anna , McCollum Eric D.
Published: August 2024

Acute lower respiratory infections (ALRI) are the leading post-neonatal cause of death in children under 5 years old. There is a high prevalence of pediatric ALRI-related hypoxemia in low- and middle-income countries. The WHO defines clinically meaningful hypoxemia in children as a SpO2 (peripheral oxygen saturation) <90%. Multiple studies put this convention into question and found SpO2 of 90% to 92% to be associated with child ALRI mortality. An evolving body of evidence suggests that pulse oximeters systematically overestimate oxygen saturation in individuals with dark skin tones. We conducted a narrative review of pediatric studies evaluating pulse oximeter accuracy in children without COVID-19. Four studies, one prospective, examined pulse oximeter accuracy in children of varying ages with dark skin tones. All studies had limitations that affect their generalizability. There is evidence that certain pulse oximeters may overestimate oxygen saturation in children with dark skin tones. Further prospective research is urgently needed to identify affected populations and clinical implications. Despite recognized challenges, we strongly urge continued and expanded use of pulse oximetry as its use will save lives.
Dolsko – Spodnje Škovce and a new insight into the settlement, chronology, ceramic style(s), and subsistence strategies of the Late Neolithic Sava group in Slovenia
Authors: Kramberger Bine , Toškan Borut , Tolar Tjaša
Published: August 2024

Radiocarbon dates, analysis of ceramic finds, animal bones, fruits/seeds and wood (charcoal) from settlement features of the Sava group of the Lengyel Culture at the site of Dolsko – Spodnje Škovce in central Slovenia are presented and discussed in this paper. The aim of the study was to place the excavated material culture in its regional and supra-regional context in order to improve the understanding of Late Neolithic settlement features, chronology, pottery style(s) and subsistence strategies in settlements throughout the area of distribution of the Sava group. This is the first synthesis of archaeobotanical and archaeozoological data from the 5th millennium cal BC sites in Slovenia, including the evaluation and comparison of plant macro-remains and animal bones, and the first synthesis of data on technological and typological aspects of pottery production in the settlements obtained using the same analytical approach. Uncertainties regarding the chronology of different variations of a pottery style and subsistence strategies are emphasized.
Late Upper Palaeolithic ornaments from Vlakno cave, Croatia
Authors: Cvitkušić Barbara , Cristiani Emanuela , Vujević Dario
Published: August 2024

This paper presents the richest prehistoric assemblage of ornaments in the Eastern Adriatic discovered to date, found in the Late Upper Palaeolithic layers of Vlakno cave, Croatia. The abundance and multiform of bead types indicate that the site was likely used as a workshop for ornaments, i.e. that production was performed on site. Technological and use-wear analysis of each taxon used for beads allowed us to elaborate on its mode of production, use, and overall position of the Vlakno cave site and its role in the regional context during the Late Pleistocene.
Emotions and Strategies in the Face of the Border(ing): The Lived Experiences of Filipino Migrants in Mainland China
Authors: Kujawa Izabela
Published: August 2024

Even though the People’s Republic of China is still considered a country of emigration rather than immigration, there is a growing number of foreigners who move there for work. In this article, I explore the lived experiences of migrants originating from the Philippines. I focus on their understanding of and affective encounters with the border and with bordering practices. Furthermore, I analyze the strategies these migrants employ to navigate their situations and secure their stay in the country. By doing so, I aim to contribute to the flourishing literature on the situation of migrants based in Mainland China, and to an understanding of the on-the-ground consequences of the Chinse immigration system’s regulations and practices. Based on 20 in-depth interviews, I argue that migration is not merely related to the migrants’ rational decisions and their execution thereof, but rather, that the whole process is accompanied by a range of emotions, varying in kind, intensity, and anchorage. For the Filipinas and Filipinos interviewed here, despite their differences, the strongest reactions were caused by the shape of the state regulations in place, which were perceived as a source of the sense of insecurity and instability.
Orientacje akulturacyjne Meksykanów w stosunku do migrantów pochodzących z USA, Francji, Polski, Hiszpanii, Korei Południowej i Ekwadoru
Authors: Golińska  , Kwiatkowska
Published: August 2024

Celem badania było znalezienie odpowiedzi na pytanie, jak Meksykanie (obywatele państwa goszczącego) postrzegają strategie akulturacyjne obcokrajowców, przybywających do Meksyku (płaszczyzna realna), oraz jakie są ich oczekiwania względem akulturacji przybyszy (płaszczyzna idealna). Ramy teoretyczne badania tworzy Relatywny Model Względnej Akulturacji (RAEM) (Navas i in. 2005). Próba liczyła 363 osób w wieku od 17 do 72 lat (M = 25,92; SD = 11,97). W badaniu udział wzięły przeze wszystkim osoby młode. Respondentów proszono o ustosunkowanie się do przybyszy pochodzących z krajów o różnym dystansie kulturowym wobec Meksyku, tj. z USA, Francji, Polski, Hiszpanii, Korei Południowej i Ekwadoru. W płaszczyźnie realnej Meksykanie sądzą, iż obcokrajowcy w sferach publicznych stosują integrację (z wyjątkiem Korei Południowej, dla której zidentyfikowano mieszaną strategię integracji i separacji), zaś w prywatnych sferach integrację i/lub separację. W płaszczyźnie idealnej Meksykanie oczekują od gości z USA, Francji, Polski i Korei Południowej separacji w sferach publicznych oraz separacji/integracji od Hiszpanów (dla Ekwadoru nie można było przyporządkować jednoznacznie żadnej z orientacji akulturacyjnych); zaś w prywatnych sferach życia oczekiwano integracji obcokrajowców z sześciu badanych krajów. Wykazano, iż Meksykanie postrzegają
Navigating Cross-Cultural Challenges: A Phenomenological Study on Strategies for International Faculty in Higher Education to Support Local Students
Authors: Ndiangui Peter , Zhang Jingshun , Ozfidan Burhan , Halpern Clarisse
Published: August 2024

Dealing with local challenges and providing effective support for students as an international faculty member can be both challenging and rewarding. This phenomenological study delved into the intricate dynamics of cross-cultural encounters within higher education settings, focusing on the experiences of international faculty in supporting local students. Using semi-structured focus group meetings, the researchers explored how their lived experiences as full‐time international faculty working in institutions of higher learning in the United States could be applied in providing support for students. This process required intricate navigation to acquire some level of cultural understanding of the local culture and traditions and build relationships with native faculty, staff, and students. The study was based on firsthand experiences of how the authors, international scholars from various parts of the world, navigated through these hurdles to become effective educators. The researchers constructed generalizations, noting that the institutions whose policies include embracing cultural diversity, fostering inclusivity, and providing targeted support are better positioned to enable their international faculty members to address local challenges and empower students to succeed effectively.
Reservoir Potential Evaluation of the Middle Paleocene Lockhart Limestone of the Kohat Basin, Pakistan: Petrophysical Analyses
Authors: Khan Nasar , Ahmad Imran , Ishaq Muhammad , Jan Irfan , Khan Wasim , Awais Muhammad , Salam Mohsin , Khan Bilal
Published: August 2024

The Lockhart Limestone is evaluated for its reservoir potential by utilizing wireline logs of Shakardara-01well from Kohat Basin, Pakistan. The analyses showed 28.03% average volume of shale (Vsh), 25.57% average neutron porosity (NPHI), 3.31% average effective porosity (PHIE), 76% average water saturation (Sw), and 24.10% average hydrocarbon saturation (Sh) of the Lockhart Limestone in Shakardara-01 well. Based on variation in petrophysical character, the reservoir units of the Lockhart Limestone are divided into three zones i.e., zone-1, zone-2 and zone-3. Out of these zones, zone-1 and zone-2 possess a poor reservoir potential for hydrocarbons as reflected by very low effective porosity (1.40 and 2.02% respectively) and hydrocarbon saturation (15 and 5.20%), while zone-3 has a moderate reservoir potential due to its moderate effective porosity (6.50%) and hydrocarbon saturation (52%) respectively. Overall, the average effective porosity of 3.31% and hydrocarbon saturation of 24.10% as well as 28.03% volume of shale indicated poor reservoir potential of the Lockhart Limestone. Lithologically, this formation is dominated by limestone and shale interbeds in the Shakardara-01 well. Cross-plots of the petrophysical parameters versus depth showed that the Lockhart Limestone is a poor to tight reservoir in Shakardara-01 well and can hardly produce hydrocarbons under conventional drilling conditions.
ASPECTOS RELEVANTES DE LA FINANCIACIÓN AUTONÓMICA: ANÁLISIS ECONÓMICO DE LA ADMINISTRACIÓN PÚBLICA EN RELACIÓN CON LA FINANCIACIÓN AUTONÓMICA
Authors: REINA MARTÍN MARÍA DOLORES
Published: August 2024

La presente publicación realiza un planteamiento del proceso de financiación autonómica, arrancando de la teoría del federalismo fiscal y llegando al marco de la nueva financiación autonómica.
Retinopatia da prematuridade: uma revisão de literatura
Authors: Pereira Ana Caroline Prado , Queiroz João Marcelo Lima , Tomé Lia Santoro Alves , Bazzo Estênio Grubert , Cunha Maria Rita Rodrigues da
Published: August 2024

A Retinopatia da Prematuridade (ROP) é uma doença ocular que afeta neonatos prematuros, sendo uma das principais causas de cegueira infantil evitável. Este artigo revisa sistematicamente a literatura sobre ROP, focando na epidemiologia, fisiopatologia, diagnóstico, tratamento e prevenção. Utilizamos bases de dados eletrônicas para identificar estudos relevantes, priorizando publicações brasileiras. Os resultados apontam para a importância do diagnóstico precoce e tratamento adequado para prevenir a progressão da doença. Concluímos que, apesar dos avanços significativos, desafios persistem na prevenção e manejo da ROP, exigindo esforços contínuos em pesquisa e políticas de saúde.
Belantamabe-Mafodotina, um novo agente para mieloma, causando ceratopatia tóxica: relato de caso e revisão da literatura
Authors: Alari Giovani Romero , Melo Carolina Cardoso de , Cunha Dara Paschoal da , Pirovani Júnior Carlos Miguel , Lira Mirella Cruz
Published: August 2024

Belantamabe-mafodotina é um agente terapêutico inovador para o tratamento de mieloma múltiplo, recentemente associado à ceratopatia tóxica em alguns pacientes. Este artigo apresenta um relato de caso de ceratopatia tóxica induzida por belantamabe-mafodotina e uma revisão sistemática da literatura brasileira sobre o tema. A análise detalha os mecanismos de ação, eficácia terapêutica, perfil de segurança, e impacto clínico da ceratopatia tóxica. Foram incluídos estudos publicados entre 2010 e 2023, utilizando bases de dados como PubMed, SciELO, e LILACS. Os resultados sugerem a necessidade de monitoramento oftalmológico rigoroso em pacientes tratados com belantamabe-mafodotina. Concluímos que, embora eficaz no controle do mieloma múltiplo, a ceratopatia tóxica representa um desafio significativo que deve ser cuidadosamente gerenciado.
Tratamento anti-inflamatório após trabeculoplastia seletiva a laser: revisão sistemática da literatura e meta-análise de ensaios clínicos randomizados controlados
Authors: Vilela Ana Luiza Oliveira , Amorim Adriane Machado , Silva Letícia Albano Hipólito da , Santos Filho Daniel Francisco dos , Machado Renato de Souza Susanna
Published: August 2024

A trabeculoplastia seletiva a laser (SLT) é uma intervenção amplamente utilizada no tratamento do glaucoma de ângulo aberto. No entanto, o uso de agentes anti-inflamatórios pós-operatórios permanece controverso. Este estudo tem como objetivo realizar uma revisão sistemática da literatura e uma meta-análise de ensaios clínicos randomizados controlados (ECRs) para avaliar a eficácia e a segurança dos tratamentos anti-inflamatórios após a SLT. Foram incluídos estudos publicados até 2023 nas bases de dados PubMed, Scielo e LILACS. A revisão identificou um total de 12 ECRs que atenderam aos critérios de inclusão. A análise demonstrou que o uso de anti-inflamatórios pós-SLT está associado a uma redução significativa na inflamação ocular sem comprometer a eficácia da SLT. Concluímos que o tratamento anti-inflamatório após SLT é benéfico para os pacientes, com um perfil de segurança aceitável.
Oclusão da artéria central da retina associada ao forame oval patente: relato de caso e revisão de literatura
Authors: Dallazen Eduardo , Oliveira Ana Clara Benites Ciani de Carvalho , Miki Leonardo Naoki Maciel , Silva Filho Renato Lucio da , Faria Caroline de
Published: August 2024

A oclusão da artéria central da retina (OACR) é uma condição oftalmológica rara e grave, frequentemente associada a fatores de risco cardiovasculares. O forame oval patente (FOP), uma comunicação interatrial persistente após o nascimento, tem sido implicado como um possível fator contribuinte para eventos tromboembólicos, incluindo a OACR. Este artigo apresenta um relato de caso de um paciente com OACR associado ao FOP, seguido de uma revisão sistemática da literatura sobre a relação entre essas duas condições. A revisão incluiu artigos indexados nas bases de dados SciELO, LILACS e PubMed. Os resultados indicam uma possível correlação entre FOP e OACR, sugerindo a necessidade de maior atenção ao diagnóstico e manejo desses pacientes.
Comportamento suicida em indivíduos com esclerose lateral amiotrófica: uma revisão sistemática
Authors: Machado Beatriz Jorge Macedo de , Pires Leonardo Lucas , Costa Bárbara Fernanda Pacheco da , Pedroso Gustavo Henrique
Published: August 2024

Introdução: A esclerose lateral amiotrófica (ELA) é uma doença neurodegenerativa caracterizada pela destruição de neurônios motores, levando à perda progressiva da capacidade motora. O impacto emocional do diagnóstico e as limitações impostas pela doença podem aumentar o risco de comportamentos suicidas entre os pacientes. Objetivo: Este artigo revisa a literatura sobre os fatores de risco associados ao comportamento suicida em pacientes com ELA, propondo estratégias para reduzir o sofrimento psíquico. Materiais e métodos: Foram incluídos estudos publicados entre 2014 e 2024 nas bases PubMed, Scopus, Web of Science, PsycINFO e Google Scholar. Resultados e discussão: Pacientes com ELA apresentam maior risco de comportamento suicida, especialmente nas fases iniciais da doença, sendo a depressão um fator de risco importante. Considerações finais: A abordagem multidisciplinar e o suporte psicossocial são essenciais para minimizar o sofrimento desses pacientes.