bluuebunny/crossref_metadata_2025 huggingface dataset:
Determinants and willingness to practice obstetric analgesia among women attending antenatal clinic at Dr. Bogalech Gebre Memorial General Hospital Central Ethiopia: a cross-sectional study
Authors: Geltore Teketel Ermias , Alemu Getachew , Taye Ayanos , Sileshi Eden , Bekele Merkin , Foto Lakew Lafebo
Published: July 2024

Background

Labor pain is uniquely experienced and described by the woman giving birth, and it is often considered one of the most excruciating experiences for many women. This study aimed to evaluate factors associated with the willingness to receive labor analgesia among women attending the antenatal clinic at Dr. Bogalech Gebre Memorial General Hospital Central Ethiopia in 2022.

Methods

An institution-based, cross-sectional study was conducted from January to March 2022. Data were collected using semi-structured questionnaires by a convenience sampling technique. Data was entered in EpiData 4.2 and exported to SPSS version 20 for analysis. Both Bivariable and multivariable logistic regressions were conducted to determine factors associated with pregnant women’s willingness to choose labor analgesia. Crude odds ratio (COR) and adjusted odds ratio (AOR) were computed to assess the association between variables.

Results

A total of 398 pregnant women have participated in the study with a response rate of 94%. Nearly 30%, (29.4%) of the pregnant women had a willingness to practice labor pain management. Being a housewife (AOR: 8.35, 95% CI: 2.07, 33.63). Women who live in urban (AOR: 2.60, 95% CI: 1.29, 5.29). Having had awareness about labor analgesia (AOR: 1.70, 95% CI: 1.00, 2.60) and the short duration of labor time (AOR: 1.84, 95% CI: 1.15, 2.96) were statistically significant with a willingness to practice labor analgesia.

Conclusion

We conclude that the willingness of pregnant mothers’ toward obstetric analgesia practice was low in the study area. Being a housewife, urban residence, awareness about labor analgesia, and short duration of labor were statistically significant with the willingness of the mothers to practice labor analgesia. To increase willingness to use labor analgesia, authorities should prioritize delivering health education on pain management choices to address concerns and promote effective methods and practices.
Influence of cryoablation versus operation on circulating lymphocyte subsets in patients with early-stage renal cell carcinoma
Authors: Waidhauser Johanna , Gantner Anna-Katharina , Schifano Paola , Rippel Katharina , Schiele Stefan , Arndt Tim Tobias , Müller Gernot , Steinestel Julie , Rank Andreas , Kröncke Thomas
Published: July 2024

Immune response is known to play an important role in local tumor control especially in renal cell carcinoma (RCC), which is considered highly immunogenic. For localized tumors, operative resection or local ablative procedures such as cryoablation are common therapeutical options. For thermal ablative procedures such as cryoablation, additional immunological anti-tumor effects have been described.

The purpose of this prospective study was to determine changes in peripheral blood circulating lymphocytes and various of their subsets in RCC patients treated with cryoablation or surgery in a longitudinal approach using extensive flow cytometry. Additionally, lymphocytes of RCC patients were compared to a healthy control group.

We included 25 patients with RCC. Eight underwent cryoablation and 17 underwent surgery. Univariate and multivariable analysis revealed significantly lower values of B cells, CD4 and CD8 T cells, and various of their subsets in the treatment groups versus the healthy control group. Comparing the two different therapeutical approaches, a significant decline of various lymphocyte subsets with a consecutive normalization after three months was seen for the surgery group, whereas cryoablation led to increased values of CD69 + CD4 + and CD69 + CD8 + cell counts as well as memory CD8 + cells after three months.

Treatment-naïve RCC patients showed lower peripheral blood lymphocyte counts compared to healthy controls. The post-treatment course revealed different developments of lymphocytes in the surgery versus cryoablation group, and only cryoablation seems to induce a sustained immunological response after three months.
Refractory type 1 plastic bronchitis in a child; case report
Authors: Elmeazawy Rehab , Elniny Ahmed
Published: July 2024

Background

Plastic bronchitis (PB) is a rare pediatric pulmonary condition characterized by the production of branching bronchial casts that cause partial or total obstruction of the bronchial lumen.

Case presentation

We describe a 13-year-old boy with a history of bronchial asthma and left lower lobectomy, with persistent cough and left-sided chest pain when he went to the emergency room. Chest radiography showed complete left lung opacity denoting total left lung collapse, and flexible bronchoscopy revealed cohesive casts totally occluding the left bronchus, with frequent recurrence that finally ended with left pneumonectomy.

Conclusion

Plastic bronchitis is a rare, fatal disease in children that requires a high index of suspicion for both diagnosis and treatment. Although bronchoscopic removal of the bronchial casts together with the medical treatment are the main lines of treatment, cases with recurrent formation of casts are at high risk for surgical intervention in the form of either lobectomy or pneumonectomy.
Social support and economic conditions among older migrants in India: do distance, duration, and streams of migration play a role in later life?
Authors: Ahamad Vasim , Bhagat Ram Babu , Manisha  , Pal Sanjay Kumar
Published: July 2024

Background

Being older and having a migrant feature might cause a double risk of vulnerability in poor economic, social support, and health status at the place of destination. This study examines the association of migration on the social support and economic condition of older persons in India.

Methods

Longitudinal Ageing Study in India (LASI) wave-I (2017–2018) data with total samples of 66,156 older adults aged 45 + with 30,869 and 35,287 male and female samples, respectively, used in this study. Descriptive and bivariate analyses have been performed to examine the pattern of older migrants, and multinomial logistic regression analysis has been used to establish the associations between migration, social support, and economic condition.

Results

Over half (57.5%) of the population aged 45 + in India had migrant characteristics; 80% migrated before 25 years. Of all migrants, about 90% migrated within one state (Intrastate), and 9% migrated to another (Interstate). The association between social support and migration by distance and the adjusted result showed that immigrants were less likely to have medium [RRR = 0.56 (CI; 0.46–0.68)] and high [RRR = 0.39 (CI; 0.30–0.50)] social support. The interstate migrants were also less likely to have high [RRR = 0.90 (CI; 0.83–0.98)] social support. The migrants with 0–9 years of duration were less likely to have high social support, and the urban to rural stream migrants were more likely to have high social support. The association between economic status and migration by distance and the adjusted result showed that more affluent immigrants were likelier to have [RRR = 1.41 (CI; 1.14–1.73)] better economic conditions than affluent non-migrants. Migrants with 0–9-year duration and urban to rural stream were found to be likelier to have better economic conditions.

Conclusions

The findings of this study suggest that distance, duration, and migration stream have a significant association with social support and economic conditions in later life. In exploring migration’s effect on social and economic status, policymakers should prioritize migrants in their agenda to maintain socio-economic and social support for older persons in India to achieve the sustainable goal of active and healthy ageing.
Trends in alcohol use and alcoholic liver disease in South Korea: a nationwide cohort study
Authors: Yoo Jeong-Ju , Lee Dong Hyeon , Chang Young , Jo Hoongil , Cho Young Youn , Lee Sangheun , Kim Log Young , Jang Jae Young ,   the Korean Association for the Study of the Liver
Published: July 2024

Background

There is a lack of national-level research on alcohol consumption and the epidemiology of alcoholic liver disease (ALD) in South Korea. This study aims to address the critical public health issue of ALD by focusing on its trends, incidence, and outcomes, using nationwide claims data.

Methods

Utilizing National Health Insurance Service data from 2011 to 2017, we calculated the population's overall drinking amount and the incidence of ALD based on ICD-10 diagnosis codes.

Results

From 2011 to 2017 in South Korea, social drinking increased from 15.7% to 16.5%, notably rising among women. High-risk drinking remained around 16.4%, decreasing in men aged 20–39 but not decreased in men aged 40–59 and steadily increased in women aged 20–59. The prevalence of ALD in high-risk drinkers (0.97%) was significantly higher than in social drinkers (0.16%). A 3-year follow-up revealed ALD incidence of 1.90% for high-risk drinkers and 0.31% for social drinkers. Women high-risk drinkers had a higher ALD risk ratio (6.08) than men (4.18). The economic burden of ALD was substantial, leading to higher healthcare costs and increased hospitalization. Progression rates to liver cirrhosis and hepatocellular carcinoma (HCC) in ALD patients were 23.3% and 2.8%, respectively, with no gender difference in cirrhosis progression.

Conclusions

The study revealed a concerning rise in alcohol consumption among South Korean women and emphasizes the heightened health risks and economic burdens associated with high-risk drinking, especially concerning ALD and its complications.
Analysis of risk factors of postoperative complication for non-small cell lung cancer
Authors: Motono Nozomu , Mizoguchi Takaki , Ishikawa Masahito , Iwai Shun , Iijima Yoshihito , Uramoto Hidetaka
Published: July 2024

Background

The relationship between risk factors of common postoperative complications after pulmonary resection, such as air leakage, atelectasis, and arrhythmia, and patient characteristics, including nutritional status or perioperative factors, has not been sufficiently elucidated.

Methods

One thousand one hundred thirty-nine non-small cell lung cancer patients who underwent pulmonary resection were retrospectively analyzed for risk factors of common postoperative complications.

Results

In a multivariate analysis, male sex (P = 0.01), age ≥ 65 years (P < 0.01), coexistence of chronic obstructive pulmonary disease (COPD) (P < 0.01), upper lobe (P < 0.01), surgery time ≥ 155 min (P < 0.01), and presence of lymphatic invasion (P = 0.01) were significant factors for postoperative complication. Male sex (P < 0.01), age ≥ 65 years (P = 0.02), body mass index (BMI) < 21.68 (P < 0.01), coexistence of COPD (P = 0.02), and surgery time ≥ 155 min (P = 0.01) were significant factors for severe postoperative complication. Male sex (P = 0.01), BMI < 21.68 (P < 0.01), thoracoscopic surgery (P < 0.01), and surgery time ≥ 155 min (P < 0.01) were significant risk factors for postoperative air leakage. Coexistence of COPD (P = 0.01) and coexistence of asthma (P < 0.01) were significant risk factors for postoperative atelectasis. Prognostic nutrition index (PNI) < 45.52 (P < 0.01), lobectomy or extended resection more than lobectomy (P = 0.01), and surgery time ≥ 155 min (P < 0.01) were significant risk factors for postoperative arrhythmia.

Conclusion

Low BMI, thoracoscopic surgery, and longer surgery time were significant risk factors for postoperative air leakage. Coexistence of COPD and coexistence of asthma were significant risk factors for postoperative atelectasis. PNI, surgery time, and surgical procedure were revealed as risk factors of postoperative arrhythmia. Patients with these factors should be monitored for postoperative complication.

Trial registration

The Institutional Review Board of Kanazawa Medical University approved the protocol of this retrospective study (approval number: I392), and written informed consent was obtained from all patients.
Performance of risk scores in predicting mortality at 3, 6, and 12 months in patients diagnosed with community-acquired pneumonia
Authors: Tuta-Quintero Eduardo , Bastidas Alirio R. , Guerrón-Gómez Gabriela , Perna-Reyes Isabella , Torres Daniela , Garcia Laura , Villanueva Javier , Acuña Camilo , Mikler Eathan , Arcila Juan , Chavez Nicolas , Riviera Allison , Maldonado Valentina , Galindo María , Fernández María , Schloss Carolina , Reyes Luis Felipe
Published: July 2024

Background

Risk scores (RS) evaluate the likelihood of short-term mortality in patients diagnosed with community-acquired pneumonia (CAP). However, there is a scarcity of evidence to determine the risk of long-term mortality. This article aims to compare the effectiveness of 16 scores in predicting mortality at three, six, and twelve months in adult patients with CAP.

Methods

A retrospective cohort study on individuals diagnosed with CAP was conducted across two hospitals in Colombia. Receiver Operating Characteristic (ROC) curves were constructed at 3, 6, and 12 months to assess the predictive ability of death for the following scoring systems: CURB-65, CRB-65, SCAP, CORB, ADROP, NEWS, Pneumonia Shock, REA-ICU, PSI, SMART-COP, SMRT-CO, SOAR, qSOFA, SIRS, CAPSI, and Charlson Comorbidity Index (CCI).

Results

A total of 3688 patients were included in the final analysis. Mortality at 3, 6, and 12 months was 5.2%, 8.3%, and 16.3% respectively. At 3 months, PSI, CCI, and CRB-65 scores showed ROC curves of 0.74 (95% CI: 0.71–0.77), 0.71 (95% CI: 0.67–0.74), and 0.70 (95% CI: 0.66–0.74). At 6 months, PSI and CCI scores showed performances of 0.74 (95% CI: 0.72–0.77) and 0.72 (95% CI: 0.69–0.74), respectively. Finally at 12 months, all evaluated scores showed poor discriminatory capacity, including PSI, which decreased from acceptable to poor with an ROC curve of 0.64 (95% CI: 0.61–0.66).

Conclusion

When predicting mortality in patients with CAP, at 3 months, PSI, CCI, and CRB-65 showed acceptable predictive performances. At 6 months, only PSI and CCI maintained acceptable levels of accuracy. For the 12-month period, all evaluated scores exhibited very limited discriminatory ability, ranging from poor to almost negligible.
Minimally invasive approach in a rare emergency surgery, gallbladder perforation
Authors: Aydoğdu Yunushan Furkan , Gülçek Emre , Koyuncuoğlu Ahmet Can , Büyükkasap Çağrı , Dikmen Kürşat
Published: July 2024

Background

Gallbladder perforations are challenging to manage for surgeons due to their high morbidity and mortality, rarity, and surgical approach. Laparoscopic cholecystectomy (LC) is now included with open cholecystectomy in surgical managing gallbladder perforations. This study aimed to evaluate the factors affecting conversion from laparoscopic to open cholecystectomy in cases of type I gallbladder perforation according to the Modified Niemeier classification.

Methods

Patients who met the inclusion criteria were divided into two groups: LC and conversion to open cholecystectomy (COC). Demographic, clinical, radiologic, intraoperative, and postoperative factors were compared between groups.

Results

This study included 42 patients who met the inclusion criteria, of which 28 were in the LC group and 14 were in the COC group. Their median age was 68 (55–85) years. Age did not differ significantly between groups (p = 0.218). However, the sex distribution did differ significantly between groups (p = 0.025). The location of the perforation differed significantly between groups (p < 0.001). In the LC group, 22 patients were perforated from the fundus, four from the trunk, and two from the neck. In the COC group, two patients were perforated from the fundus, four from the trunk, and eight from the neck. Surgical procedure times differed significantly between the LC (105.0 min [60–225]) and COC (125.0 min [110–180]) groups (p = 0.035). The age of the primary surgeons also differed significantly between the LC (42 years [34–63]) and COC (55 years [36–59]) groups (p = 0.001).

Conclusions

LC can be safely performed for modified Niemeier type I gallbladder perforations. The proximity of the perforation site to Calot’s triangle, Charlson comorbidity index (CCI), and Tokyo classification are factors affecting conversion from laparoscopic to open surgery of gallbladder perforations.
Diacerein mitigates endocrine and cardio-metabolic disruptions in experimental PCOS mice model by modulating AdipoR1/ PON 1
Authors: Shah Mohd Zahoor ul haq , Shrivastava Vinoy Kumar , Muzamil Showkeen , Olaniyi Kehinde S.
Published: July 2024

Background

This study aimed to explore the impact of Diacerein (DIC) on endocrine and cardio-metabolic changes in polycystic ovarian syndrome (PCOS) mouse model.

Methods

A total of 18 adult female mice (Parkes strain), aged 4–5 weeks, were randomly assigned to three groups, each comprising 6 animals, as follows: Group I (control), received normal diet and normal saline as vehicle for 51 days; Group II received Letrozole (LET; 6 mg/kg bw) for 21 days to induce PCOS; Group III received LET, followed by daily oral gavage administration of DIC (35 mg/kg bw) for 30 days.

Results

This study indicates that treatment with LET resulted in PCOS with characteristics such as polycystic ovaries, elevated testosterone, weight gain, visceral adiposity, high levels of insulin as well as fasting blood glucose in addition to insulin resistance, improper handling of ovarian lipids, atherogenic dyslipidemia, impaired Na + /K + -ATPase activity and serum, cardiac, and ovarian oxidative stress. Serum/ovarian adiponectin levels were lowered in LET-treated mice. In mice treated with LET, we also discovered a reduction in cardiac and serum paraoxonase 1 (PON1). Interestingly, DIC restored ovarian andcardio-metabolic abnormalities in LET-induced PCOS mice. DIC prevented the endocrine and cardio-metabolic changes brought on by letrozole-induced PCOS in mice.

Conclusion

The ameliorative effects of DIC on letrozole-induced PCOS with concurrent oxidative stress, abdominal fat deposition, cardiac and ovarian substrate mishandling, glucometabolic dysfunction, and adiponectin/PON1 activation support the idea that DIC perhaps, restore compromised endocrine and cardio-metabolic regulators in PCOS.
Metabolic profiling and enzyme inhibitory activity of the essential oil of citrus aurantium fruit peel
Authors: Ashmawy Naglaa S. , Nilofar Nilofar , Zengin Gokhan , Eldahshan Omayma A.
Published: July 2024

Background

Bitter orange (Citrus aurantium) is a fruiting shrub native to tropical and subtropical countries around the world and cultivated in many regions due to its nutraceutical value. The current study investigated the metabolic profiling and enzyme inhibitory activities of volatile constituents derived from the C. aurantium peel cultivated in Egypt by three different extraction methods.

Methods

The volatile chemical constituents of the peel of C. aurantium were isolated using three methods; steam distillation (SD), hydrodistillation (HD), and microwave-assisted hydrodistillation (MAHD), and then were investigated by GC-MS. The antioxidant potential was evaluated by different assays such as DPPH, ABTS, FRAP, CUPRAC, and phosphomolybdenum and metal chelating potential. Moreover, the effect of enzyme inhibition of the three essential oils was tested using BChE, AChE, tyrosinase, glucosidase, as well as amylase assays.

Results

A total of six compounds were detected by GC/MS analysis. The major constituent obtained by all three extraction methods was limonene (98.86% by SD, 98.68% by HD, and 99.23% by MAHD). Differences in the composition of the compounds of the three oils were observed. The hydrodistillation technique has yielded the highest number of compounds, notably two oxygenated monoterpenes: linalool (0.12%) and α-terpineol acetate (0.1%).

Conclusion

In our study differences in the extraction methods of C. aurantium peel oils resulted in differences in the oils’ chemical composition. Citrus essential oils and their components showed potential antioxidant, anticholinesterase, antimelanogenesis, and antidiabetic activities. The presence of linalool and α-terpineol acetate may explain the superior activity observed for the oil isolated by HD in both radical scavenging and AChE inhibition assays, as well as in the enzyme inhibition assays.
Bioactivity and antibacterial effect of star anise biosynthesized silver nanoparticles against Streptococcus mutans: an in vitro study
Authors: Elchaghaby Marwa Aly , Rashad Sayed , Wassef Nada Mohamed
Published: July 2024

Background

Silver nanoparticles (AgNPs) are receiving a lot of attention as a prospective antibacterial agent for use in caries prevention. The objective of this study was to investigate the bioactivity and antibacterial effect of silver nanoparticles biosynthesized using Star Anise against Streptococcus mutans (S.mutans).

Methods

The bioactive components of the Star Anise were assessed by employing the gas chromatography-mass spectrometry technique. The antibacterial activities of Star Anise Biosynthesized Silver Nanoparticles against S.mutans bacteria were evaluated using Bauer and Kirby’s disc diffusion mechanism and the minimum inhibitory concentration.

Results

Silver nanoparticles biosynthesized using Star Anise revealed high antioxidant activity. AgNPs inhibited S. mutans with a 16 mm inhibition zone diameter and demonstrated an 80 µg/ml minimum inhibitory concentration.

Conclusions

Biologically synthesized AgNPs made from aqueous extract of Star anise appear to be a potential and effective bactericidal agent against S.mutans that can be used to prevent dental caries.
Metabolic score for insulin resistance (METS-IR) predicts all-cause and cardiovascular mortality in the general population: evidence from NHANES 2001–2018
Authors: Duan Mingxuan , Zhao Xi , Li Shaolin , Miao Guangrui , Bai Linpeng , Zhang Qingyang , Yang Wenxuan , Zhao Xiaoyan
Published: July 2024

Background

The prevalence of obesity-associated insulin resistance (IR) is increasing along with the increase in obesity rates. In this study, we compared the predictive utility of four alternative indexes of IR [triglyceride glucose index (TyG index), metabolic score for insulin resistance (METS-IR), the triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio and homeostatic model assessment of insulin resistance (HOMA-IR)] for all-cause mortality and cardiovascular mortality in the general population based on key variables screened by the Boruta algorithm. The aim was to find the best replacement index of IR.

Methods

In this study, 14,653 participants were screened from the National Health and Nutrition Examination Survey (2001–2018). And TyG index, METS-IR, TG/HDL-C and HOMA-IR were calculated separately for each participant according to the given formula. The predictive values of IR replacement indexes for all-cause mortality and cardiovascular mortality in the general population were assessed.

Results

Over a median follow-up period of 116 months, a total of 2085 (10.23%) all-cause deaths and 549 (2.61%) cardiovascular disease (CVD) related deaths were recorded. Multivariate Cox regression and restricted cubic splines analysis showed that among the four indexes, only METS-IR was significantly associated with both all-cause and CVD mortality, and both showed non-linear associations with an approximate “U-shape”. Specifically, baseline METS-IR lower than the inflection point (41.33) was negatively associated with mortality [hazard ratio (HR) 0.972, 95% CI 0.950–0.997 for all-cause mortality]. In contrast, baseline METS-IR higher than the inflection point (41.33) was positively associated with mortality (HR 1.019, 95% CI 1.011–1.026 for all-cause mortality and HR 1.028, 95% CI 1.014–1.043 for CVD mortality). We further stratified the METS-IR and showed that significant associations between METS-IR levels and all-cause and cardiovascular mortality were predominantly present in the nonelderly population aged < 65 years.

Conclusions

In conjunction with the results of the Boruta algorithm, METS-IR demonstrated a more significant association with all-cause and cardiovascular mortality in the U.S. population compared to the other three alternative IR indexes (TyG index, TG/HDL-C and HOMA-IR), particularly evident in individuals under 65 years old.
Optimization of biotransformation processes of Camarosporium laburnicola to improve production yields of potent telomerase activators
Authors: Küçüksolak Melis , Çoban Hasan Buğra , Bedir Erdal
Published: July 2024

Background

Telomerase activators are promising agents for the healthy aging process and the treatment/prevention of short telomere-related and age-related diseases. The discovery of new telomerase activators and later optimizing their activities through chemical and biological transformations are crucial for the pharmaceutical sector. In our previous studies, several potent telomerase activators were discovered via fungal biotransformation, which in turn necessitated optimization of their production. It is practical to improve the production processes by implementing the design of experiment (DoE) strategy, leading to increased yield and productivity. In this study, we focused on optimizing biotransformation conditions utilizing Camarosporium laburnicola, a recently discovered filamentous fungus, to afford the target telomerase activators (E-CG-01, E-AG-01, and E-AG-02).

Results

DoE approaches were used to optimize the microbial biotransformation processes of C. laburnicola. Nine parameters were screened by Plackett-Burman Design, and three significant parameters (biotransformation time, temperature, shaking speed) were optimized using Central Composite Design. After conducting validation experiments, we were able to further enhance the production yield of target metabolites through scale-up studies in shake flasks (55.3-fold for E-AG-01, 13-fold for E-AG-02, and 1.96-fold for E-CG-01).

Conclusion

Following a process optimization study using C. laburnicola, a significant increase was achieved in the production yields. Thus, the present study demonstrates a promising methodology to increase the production yield of potent telomerase activators. Furthermore, C. laburnicola is identified as a potential biocatalyst for further industrial utilization.
Inhibition of autophagy induced by tetrandrine promotes the accumulation of reactive oxygen species and sensitizes efficacy of tetrandrine in pancreatic cancer
Authors: Wang Yiwei , Xu Ting , Wang Hongcheng , Xia Guanggai , Huang Xinyu
Published: July 2024

Pancreatic cancer, characterized by its poor prognosis, exhibits a marked resistance to conventional chemotherapy and immunotherapy, underscoring the urgent need for more effective treatment modalities. In light of this, the present study is designed to assess the potential antineoplastic efficacy of a combined regimen involving tetrandrine, a plant-derived alkaloid, and autophagy inhibitors in the context of pancreatic cancer. Electron microscopy and immunoblots showed that tetrandrine promoted the formation of autophagosomes and the upregulation of LC3II and the downregulation of p62 expression, indicating that tetrandrine induced autophagy in pancreatic cancer cells. Western blot revealed that tetrandrine inhibited the phosphorylation of AKT and mTOR, as well as the expression of Bcl-2, while upregulating Beclin-1 expression. Moreover, tetrandrine promoted the transcription and protein expression of ATG7. Following the combination of autophagy inhibitors and tetrandrine, the apoptotic rate and cell death significantly increased in pancreatic cancer cells. Consistent results were obtained when ATG7 was silenced. Additionally, tetrandrine induced the generation of ROS, which was involved in the activation of autophagy and apoptosis. Further investigation revealed that upon autophagy inhibition, ROS accumulated in pancreatic cancer cells, resulting in decreased mitochondrial membrane potential and further induction of apoptosis. The results of treating subcutaneous xenograft tumors with a combination of tetrandrine and chloroquine validated that autophagy inhibition enhances the toxicity of tetrandrine against pancreatic cancer in vivo. Altogether, our study demonstrates that tetrandrine induces cytoprotective autophagy in pancreatic cancer cells. Inhibiting tetrandrine-induced autophagy promotes the accumulation of ROS and enhances its toxicity against pancreatic cancer.
Examining geographical inequalities for malaria outcomes and spending on malaria in 40 malaria-endemic countries, 2010–2020
Authors: Apeagyei Angela E. , Patel Nishali K. , Cogswell Ian , O’Rourke Kevin , Tsakalos Golsum , Dieleman Joseph
Published: July 2024

Background

While substantial gains have been made in the fight against malaria over the past 20 years, malaria morbidity and mortality are marked by inequality. The equitable elimination of malaria within countries will be determined in part by greater spending on malaria interventions, and how those investments are allocated. This study aims to identify potential drivers of malaria outcome inequality and to demonstrate how spending through different mechanisms might lead to greater health equity.

Methods

Using the Gini index, subnational estimates of malaria incidence and mortality rates from 2010 to 2020 were used to quantify the degree of inequality in malaria burden within countries with incidence rates above 5000 cases per 100,000 people in 2020. Estimates of Gini indices represent within-country distributions of disease burden, with high values corresponding to inequitable distributions of malaria burden within a country. Time series analyses were used to quantify associations of malaria inequality with malaria spending, controlling for country socioeconomic and population characteristics.

Results

Between 2010 and 2020, varying levels of inequality in malaria burden within malaria-endemic countries was found. In 2020, values of the Gini index ranged from 0.06 to 0.73 for incidence, 0.07 to 0.73 for mortality, and 0.00 to 0.36 for case fatality. Greater total malaria spending, spending on health systems strengthening for malaria, healthcare access and quality, and national malaria incidence were associated with reductions in malaria outcomes inequality within countries. In addition, government expenditure on malaria, aggregated government and donor spending on treatment, and maternal educational attainment were also associated with changes in malaria outcome inequality among countries with the greatest malaria burden.

Conclusions

The findings from this study suggest that prioritizing health systems strengthening in malaria spending and malaria spending in general especially from governments will help to reduce inequality of the malaria burden within countries. Given heterogeneity in outcomes in countries currently fighting to control malaria, and the challenges in increasing both domestic and international funding allocated to control and eliminate malaria, the efficient targeting of limited resources is critical to attain global malaria eradication goals.
Adverse events profile associated with intermittent fasting in adults with overweight or obesity: a systematic review and meta-analysis of randomized controlled trials
Authors: Zhong Fan , Zhu Ting , Jin Xingyi , Chen Xiangjun , Wu Ruipeng , Shao Li , Wang Shaokang
Published: July 2024

Background

There is little evidence to comprehensively summarize the adverse events (AEs) profile of intermittent fasting (IF) despite its widespread use in patients with overweight or obesity.

Methods

We searched the main electronic databases and registry websites to identify eligible randomized controlled trials (RCTs) comparing IF versus control groups. A direct meta-analysis using a fixed-effect model was conducted to pool the risk differences regarding common AEs and dropouts. Study quality was assessed by using the Jadad scale. Pre-specified subgroup and sensitivity analyses were conducted to explore potential heterogeneity.

Results

A total of 15 RCTs involving 1,365 adult individuals were included. Findings did not show a significant difference between IF and Control in risk rate of fatigue [0%, 95% confidence interval (CI), -1% to 2%; P = 0.61], headache [0%, 95%CI: -1% to 2%; P = 0.86] and dropout [1%, 95%CI: -2% to 4%; P = 0.51]. However, a numerically higher risk of dizziness was noted among the IF alone subgroup with non-early time restricted eating [3%, 95%CI: -0% to 6%; P = 0.08].

Conclusions

This meta-analysis suggested that IF was not associated with a greater risk of AEs in adult patients affected by overweight or obesity. Additional large-scale RCTs stratified by key confounders and designed to evaluate the long-term effects of various IF regimens are needed to ascertain these AEs profile.
Unmutated RRAS2 emerges as a key oncogene in post-partum-associated triple negative breast cancer
Authors: Cifuentes Claudia , Oeste Clara L. , Fernández-Pisonero Isabel , Hortal Alejandro M. , García-Macías Carmen , Hochart Jeanne , Rubira Regina , Horndler Lydia , Horndler Carlos , Bustelo Xosé R. , Alarcón Balbino
Published: July 2024

Background

Breast cancer (BC) is the most common cancer in women, with triple negative BC (TNBC) accounting for 20% of cases. While early detection and targeted therapies have improved overall life expectancy, TNBC remains resistant to current treatments. Although parity reduces the lifetime risk of developing BC, pregnancy increases the risk of developing TNBC for years after childbirth. Although numerous gene mutations have been associated with BC, no single gene alteration has been identified as a universal driver. RRAS2 is a RAS-related GTPase rarely found mutated in cancer.

Methods

Conditional knock-in mice were generated to overexpress wild type human RRAS2 in mammary epithelial cells. A human sample cohort was analyzed by RT-qPCR to measure RRAS2 transcriptional expression and to determine the frequency of both a single-nucleotide polymorphism (SNP rs8570) in the 3’UTR region of RRAS2 and of genomic DNA amplification in tumoral and non-tumoral human BC samples.

Results

Here we show that overexpression of wild-type RRAS2 in mice is sufficient to develop TNBC in 100% of females in a pregnancy-dependent manner. In human BC, wild-type RRAS2 is overexpressed in 68% of tumors across grade, location, and molecular type, surpassing the prevalence of any previously implicated alteration. Still, RRAS2 overexpression is notably higher and more frequent in TNBC and young parous patients. The increased prevalence of the alternate C allele at the SNP position in tumor samples, along with frequent RRAS2 gene amplification in both tumors and blood of BC patients, suggests a cause-and-effect relationship between RRAS2 overexpression and breast cancer.

Conclusions

Higher than normal expression of RRAS2 not bearing activating mutations is a key driver in the majority of breast cancers, especially those of the triple-negative type and those linked to pregnancy.
Macrophage-derived exosomes promote telomere fragility and senescence in tubular epithelial cells by delivering miR-155
Authors: Yin Qing , Tang Tao-Tao , Lu Xiao-Yu , Ni Wei-Jie , Yin Di , Zhang Yi-Lin , Jiang Wei , Zhang Yue , Li Zuo-Lin , Wen Yi , Gan Wei-Hua , Zhang Ai-Qing , Lv Lin-Li , Wang Bin , Liu Bi-Cheng
Published: July 2024

Background

Chronic kidney disease (CKD) is highly prevalent worldwide, and its global burden is substantial and growing. CKD displays a number of features of accelerated senescence. Tubular cell senescence is a common biological process that contributes to CKD progression. Tubulointerstitial inflammation is a driver of tubular cell senescence and a common characteristic of CKD. However, the mechanism by which the interstitial inflammation drives tubular cell senescence remains unclear. This paper aims to explore the role of exosomal miRNAs derived from macrophages in the development of tubular cell senescence.

Methods

Among the identified inflammation-related miRNAs, miR-155 is considered to be one of the most important miRNAs involved in the inflammatory response. Macrophages, the primary immune cells that mediate inflammatory processes, contain a high abundance of miR-155 in their released exosomes. We assessed the potential role of miR-155 in tubular cell senescence and renal fibrosis. We subjected miR-155−/− mice and wild-type controls, as well as tubular epithelial cells (TECs), to angiotensin II (AngII)-induced kidney injury. We assessed kidney function and injury using standard techniques. TECs were evaluated for cell senescence and telomere dysfunction in vivo and in vitro. Telomeres were measured by the fluorescence in situ hybridization.

Results

Compared with normal controls, miR-155 was up-regulated in proximal renal tubule cells in CKD patients and mouse models of CKD. Moreover, the expression of miR-155 was positively correlated with the extent of renal fibrosis, eGFR decline and p16INK4A expression. The overexpression of miR-155 exacerbated tubular senescence, evidenced by increased detection of p16INK4A/p21expression and senescence-associated β-galactosidase activity. Notably, miR-155 knockout attenuates renal fibrosis and tubule cell senescence in vivo. Interestingly, once released, macrophages-derived exosomal miR-155 was internalized by TECs, leading to telomere shortening and dysfunction through targeting TRF1. A dual-luciferase reporter assay confirmed that TRF1 was the direct target of miR-155. Thus, our study clearly demonstrates that exosomal miR-155 may mediate communication between macrophages and TECs, subsequently inducing telomere dysfunction and senescence in TECs.

Conclusions

Our work suggests a new mechanism by which macrophage exosomes are involved in the development of tubule senescence and renal fibrosis, in part by delivering miR-155 to target TRF1 to promote telomere dysfunction. Our study may provide novel strategies for the treatment of AngII-induced kidney injury.
Pornography use, demographic and sexual health characteristics among university students: a gender-based comparative study of non-users, non-problematic users, and problematic users
Authors: Pouralijan Zeinab , Bőthe Beáta , Farnam Farnaz
Published: July 2024

Background

Limited gender-based research has compared sexual health among pornography users (PUs) and non-users, including non-problematic pornography users (non-PPUs) and problematic pornography users (PPUs), particularly in non-Western cultures.

Methods

A 2022 cross-sectional study involving 450 Iranian university students categorized participants as PUs or non-users based on 12 months of use. PUs were further classified as non-PPUs or PPUs using the 'Problematic Pornography Use Scale' cutoff point, with comparisons of demographic and sexual variables made between these groups.

Results

Pornography use was reported among 39.6% of students, including 51.7% of men and 33.6% of women. In general, 9.5% of participants were PPUs, including 17.4% of men and 5.6% of women. PUs were mainly men, had fewer children, shorter marriages, lower religiosity, and lower levels of education. Compared with non-users, PUs reported earlier sexual relationships, lower satisfaction with sex frequency and communication, and greater rates of extramarital relationships, masturbation, sexual desire, and sexual distress. PPUs reported more sexual desire, pornography use, masturbation, and extramarital affairs than non-PPUs. Similar patterns in demographics, sexual history, and health were observed in pornography use across genders. The regression indicated being male (OR: 2.42, 95% CI: 1.44–4.06), having lower education (OR: 0.89, 95% CI: 0.81–0.97), fewer children (OR: 0.64, 95% CI: 0.48–0.86), higher masturbation (OR: 1.31, 95% CI: 1.14–1.49), more extramarital relationship (OR: 1.69, 95% CI: 1.07–2.67), less religiosity (OR: 0.87, 95% CI: 0.82–0.93), more sexual excitement (OR: 0.79, 95% CI:0.62–1), and more sexual distress (OR: 1.20, 95% CI: 1.02–1.32) were associated with pornography use.

Two-way ANOVA found no significant effects of gender or pornography use on sexual satisfaction. Women had worse sexual function regardless of usage. Pornography users, regardless of gender, experienced higher sexual distress.
Scarlet fever epidemics, deaths, effects on society and precautions taken in the Ottoman Empire and the Early Turkish Republic
Authors: Erkmen Ayşe , Tüzün Nevim , Erkmen Osman
Published: July 2024

Background

Scarlet fever, one of the infectious diseases, has become an epidemic in some periods and has become an epidemic in history, causing thousands of people to die. In the Ottoman Empire and the early Republic of Turkey, there was not enough literature about the prevalence of the scarlet fever epidemic, the epidemic level, the mortality status and the fight against the disease.

Methods

The effects of scarlet fever on society during the early periods of the Ottoman Empire and the Republic of Turkey, as well as the measures taken to control the disease, have been researched in Ottoman archival documents.

Results

The number of scarlet fever patients is 1225 in Anatolian settlements; 429 (35.0%) of them were children, 76 (17.7%) of the children died, and 1796 (65.0%) of them were people, 49 (6.2%) of them died. The number of scarlet fever patients is 147 in Balkan settlements; 36 (24.5%) of them were children, 6 (16.7%) of the children died, and 111 (75.5%) of them were people, 48 (43.2%) of them died. The mortality rate from scarlet fever in the Ottoman Empire was 13.0%. In Ottoman documents, the demographic structure of the society is not detailed. It is only mentioned as adults and children. In a document, it is stated that an older woman died of scarlet fever. Most documents determined that scarlet fever was seen among poor people living in villages and cities. Scarlet fever spread, and more deaths occurred in the villages, mainly due to reasons such as unhygienic conditions, separation of people, and lack of medical personnel. In the early Republic of Turkey, 8865 patients were indicated, and 1681 of them (19.0%) died.

Conclusion

The main factors causing the emergence of epidemic diseases were wars and the disruption of society’s lifestyle, socioeconomic conditions and wars.

Public Interest Summary

Epidemic diseases have had and continue to have significant effects on public health from the past to the present. In our research, it was determined that scarlet fever causes a significant number of deaths in epidemics. It has been determined that some precautions were taken against the epidemic disease, which are still valid today, but they were less adequate than today’s measures. It has been determined that measures can be developed against current and future epidemics in line with the measures taken against the same disease in the past.
Outcomes of maze procedure and mitral valve surgery in atrial functional mitral regurgitation: a retrospective study
Authors: Song Kyungsub , Jang Woo Sung , Kim Yun Seok , Yoo Jonghoon
Published: July 2024

Background

Atrial functional mitral regurgitation (AFMR) is a newly discovered condition associated with longstanding atrial fibrillation. This retrospective study aimed to analyze the outcomes of the maze procedure and mitral regurgitation (MR) surgery in AFMR and atrial fibrillation in comparison with those in degenerative MR (DMR).

Methods

Patients who underwent mitral valve repair/replacement with a maze procedure at a hospital (July 2012–August 2021) were included. We excluded patients aged below 18 years undergoing concomitant coronary artery bypass grafting or atrial septal defect repair and those with MR etiology other than ARMR or DMR.

Results

We included 35 patients with AFMR and 50 patients with DMR. Patient characteristics and postoperative outcomes were not significantly different between the two groups. Long-term outcomes revealed no significant differences in the ratio of cardiac mortality, stroke, or hospital readmission. However, after the maze procedure, the sinus rhythm restoration rate was significantly lower (62% vs. 28.5%, p < 0.001), a junctional rhythm state (p < 0.001) and permanent pacemaker insertion for sick sinus syndrome (SSS) (p = 0.03) were significantly more common in AFMR than DMR. On postoperative transthoracic echocardiography (TTE), the pulmonary artery systolic pressure was significantly less decreased in the AFMR group than in the DMR group compared with that on preoperative TTE (p = 0.04).

Conclusions

AFMR showed excellent mitral valve surgery outcomes, similar to DMR, but had a significantly higher risk of pacemaker insertion for SSS after the maze procedure.
The crosstalk between immune cells and tumor pyroptosis: advancing cancer immunotherapy strategies
Authors: Hu Mengyuan , Deng Fengying , Song Xinlei , Zhao Hongkun , Yan Fei
Published: July 2024

Pyroptosis is a cell death process characterized by cell swelling until membrane rupture and release of intracellular contents. As an effective tumor treatment strategy, inducing tumor cell pyroptosis has received widespread attention. In this process, the immune components within the tumor microenvironment play a key regulatory role. By regulating and altering the functions of immune cells such as cytotoxic T lymphocytes, natural killer cells, tumor-associated macrophages, and neutrophils, tumor cell pyroptosis can be induced. This article provides a comprehensive review of the molecular mechanisms of cell pyroptosis, the impact of the tumor immune microenvironment on tumor cell pyroptosis, and its mechanisms. It aims to gain an in-depth understanding of the communication between the tumor immune microenvironment and tumor cells, and to provide theoretical support for the development of new tumor immunotherapies.