bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and correlates of intimate partner violence among ever-married men in Uganda: a cross-sectional survey
Authors: Gubi Derrick , Wandera Stephen Ojiambo
Published: March 2022

Background

There is limited research on intimate partner violence (IPV) among ever-married men in Uganda. This paper aimed to establish the extent and correlates of emotional, sexual, and physical IPV among ever-married men in Uganda.

Methods

We used the 2016 Uganda Demographic and Health Survey (UDHS) data and selected a weighted sample of 2559 ever-married men. Frequency distributions were used to describe the characteristics of men and their partners. Chi-square tests and binary logistic regressions were used to identify factors associated with IPV among married men in Uganda.

Results

Almost half (44%) of the ever-married men experienced some form of IPV. Among the individual forms of IPV, emotional IPV was the most prevalent (36%), followed by physical IPV (20%) and sexual IPV the least common (8%). Factors that were associated with all the different forms of IPV included, region, number of wives, partners’ controlling behaviors, witnessing parental violence, and drinking alcohol as well as the frequency of getting drunk by the female partners. Except for number of wives, which had a protective effect, the rest of the factors increased the likelihood of experiencing intimate partner violence among ever-married men in Uganda.

Conclusions

Besides women, men are also victims of intimate partner violence. This calls for combined efforts to reduce violence against men perpetrated by females by addressing controlling behaviors, frequency of getting drunk with alcohol, and lack of awareness of the issue. There is a need for interventions aimed at increasing public awareness to improve the reporting and case management of violence against men and boys.
Lower workforce participation is associated with more severe persisting breathlessness
Authors: Clark Joseph , Chang Sungwon , Kinchin Irina , Ferreira Diana , Kochovska Slavica , Morgan Deidre , Poulos Leanne M. , Johnson Miriam J. , Ekström Magnus , Currow David C.
Published: March 2022

Background

Not being able to work has negative health, social and financial consequences. Persisting breathlessness is prevalent in working-aged people. Is it associated with lower workforce participation? This study, using the South Australian Health Omnibus, aimed to explore associations between paid workforce participation and persisting breathlessness intensity, and economic impacts on income in people of working age.

Methods

This cross-sectional study conducted face-to-face interviews with a random sample of adults in South Australia (n = 8916). Questions included key demographic data, workforce participation and the presence and intensity of persisting breathlessness. Data from working-aged respondents (20–65 years of age) were standardised to the census for regression analyses. Work was coded to paid full- or part-time work or ‘other’. Persisting breathlessness (more than three of the last six months) used the modified Medical Research Council breathlessness scale (aggregated to 0, 1, 2–4). Opportunity cost valuations compared annual income foregone by persisting breathlessness severity.

Results

Of people interviewed, 6,608 were working-aged (49.9% male; 67.5% had post-secondary qualifications; 70.9% were in paid full- or part-time work; and 1.7% had mMRC score 2–4). Workforce participation dropped in working aged people with increasing breathlessness: mMRC 0, 70.6%; mMRC 1, 51.7%; mMRC 2–4, 20.3%. In the regression model, people with the most severe breathlessness were much less likely to work (OR 0.14; 95% CI 0.09, 0.22). Annual income foregone by people with persisting breathlessness was AU$10.7 billion (AU$9.1b for full-time and AU$1.6b for part-time work; range AU$5.9b, AU$49.7b).

Conclusion

Worsening persisting breathlessness is associated with lower workforce participation with direct financial consequences, greatest for older males.
Systemic inflammation and sympathetic activation in gestational diabetes mellitus with obstructive sleep apnea
Authors: Serednytskyy Oleksandr , Alonso-Fernández Alberto , Ribot Caterina , Herranz Andrea , Álvarez Ainhoa , Sánchez Andrés , Rodríguez Paula , Gil Ana V. , Pía Carla , Cubero José P. , Barceló María , Cerdà María , Codina Mercedes , D. Peña Mónica , Barceló Antònia , Iglesias Amanda , Morell-Garcia Daniel , Peña José A. , Giménez María P. , Piñas María C. , García-Río Francisco
Published: March 2022

Background

Although some evidence suggests an association between obstructive sleep apnea (OSA) and gestational diabetes mellitus (GDM), its consequences still remain largely unknown. We sought to determine whether OSA is associated with higher inflammation and sympathetic levels in GDM, and to relate them with insulin resistance and perinatal outcomes.

Methods

OSA was identified by polysomnography and defined as an apnea–hypopnea index of ≥ 5 h−1. Plasma cytokines (TNF-α, IL-1β, IL-6, IL-8, IL-10), metanephrine, and normetanephrine were determined by immunoassays.

Results

We included 17 patients with GDM and OSA and 34 without OSA. Women with GDM and OSA had higher normetanephrine concentrations [81 IQR (59–134) vs. 68 (51–81) pg/mL]. No differences in the inflammatory profile were found, while IL-1β was higher in patients with mean nocturnal oxyhemoglobin saturation ≤ 94%. We found positive correlations between increased sympathetic activation and IL-1β, with obstructive apneas, while time in REM showed an inverse relationship with IL-1β and metanephrine. Furthermore, IL-10 was inversely related with time in sleep stages 1–2, and with the arousal index, and it was positively related with time in slow-wave sleep. Significant correlations were also found between IL-1β and insulin resistance. There were no significant differences in neonatal characteristics; however, we found inverse relationships between IL-10 and birth weight (BW), and percentile of BW.

Conclusions

OSA increased sympathetic activity, and IL-1β concentration was higher in patients with GDM with lower nocturnal oxygenation, all of which were related with obstructive events, and time in REM. Moreover, IL-1β was related with insulin resistance, and IL-10 inversely correlated with neonatal BW.
Syndesmotic instability can be assessed by measuring the distance between the tibia and the fibula using an ultrasound without stress: a cadaver study
Authors: Shoji Hiroaki , Teramoto Atsushi , Murahashi Yasutaka , Watanabe Kota , Yamashita Toshihiko
Published: March 2022

Background

Ultrasound examinations for syndesmosis injury might be useful for the quantitative evaluation of syndesmotic instability. The purpose of this study was to evaluate the efficacy of ultrasound assessment by measuring the tibiofibular distance of syndesmosis injuries in various ligament-injured models and stress load conditions.

Methods

Five normal ankles from Thiel-embalmed cadavers were used. Ultrasound assessment was performed by placing a probe in parallel with the ligament running just above the anterior inferior tibiofibular ligament (AITFL). The distance between the anterior border of the tibia and the fibula was measured in the intact condition. Next, Bassett’s ligament was cut arthroscopically to reduce damage to soft tissues as much as possible and measurement was performed in the same way. After that, the AITFL, interosseous membrane (IOM), deltoid ligament, and posterior inferior tibiofibular ligament (PITFL) were macroscopically cut and measured in that order. Ankle positions were without stress (natural plantar flexion without applying stress to the ankle joint), dorsiflexion stress, inversion stress, and external rotation stress. All stress to the ankle joint was carried out manually to the maximum extent.

Results

As with the without-stress condition, significant increases in tibiofibular distances after AITFL dissection were seen compared with the intact state under all stress conditions (intact: 4.9 ± 1.0 mm without stress, 5.6 ± 1.2 mm with dorsiflexion, 5.9 ± 1.0 mm with inversion, and 6.7 ± 1.3 mm with external rotation; AITFL dissection: 6.7 ± 1.5 mm without stress, 7.3 ± 1.2 mm with dorsiflexion, 7.5 ± 1.4 mm with inversion, and 8.7 ± 1.6 mm with external rotation). AITFL dissection with external rotation stress significantly increased the tibiofibular distance compared to without stress.

Conclusion

Changes in tibiofibular distance with the severity of syndesmosis injury were measured by ultrasound using cadavers. No significant change was seen with Bassett’s ligament injury, but tibiofibular distance increased significantly with injuries of equal to or greater severity than AITFL injury. Results were similar not only for external rotation stress, but also for dorsiflexion stress and inversion stress, and even in unloaded states, significant tibiofibular widening was confirmed with injuries of equal to or greater severity than AITFL injury.
Is there a role for cementless primary stem in hip arthroplasty for early or late fixation failures of intertrochanteric fractures?
Authors: Ma Hsuan-Hsiao , Chou Te-Feng Arthur , Tsai Shang-Wen , Chen Cheng-Fong , Wu Po-Kuei , Chen Wei-Ming
Published: March 2022

Background

The choice of femur stems during the hip arthroplasty procedures for patients with treatment failure of intertrochanteric fractures (ITF) remains controversial. We aimed to compare the surgical complication and reoperation rates between cementless primary and revision stems in the early (≤3 months) and late (> 3 months) fixation failures of ITF.

Methods

This was a retrospective, cohort study conducted in a single, tertiary referral hospital of Taipei, Taiwan. We included hip arthroplasty procedures for failed ITF using cementless primary or revision stems. There were 40 and 35 patients who had early and late fixation failure of ITF, respectively. The patient demographics, time to fixation failure, surgical complications and medical complications were recorded for analysis.

Results

We included 75 patients that underwent hip arthroplasty procedure for failed ITF using cementless primary (n = 38) or revision (n = 37) stems. The mean age was 79.3 years and 56% of the patients were female. In the early fixation failure group, the complication rate was similar between the primary and revision stems (44% vs. 29%, p = 0.343). However, there was a trend toward a higher reoperation rate (31% vs. 8%, p = 0.061) of using the primary stem, compared with the revision stem. In the late fixation failure group, the rate of complication and reoperation was similar between the two stem types.

Conclusion

For early fixation failures of ITFs, we caution against the use of cementless primary stems due to a trend towards an increased risk of reoperations compared to the use of cementless revision stems. However, in late fixation failures of ITFs, there is a role for cementless primary stems.

Level of evidence

III, retrospective cohort study.
Small bowel diverticula in elderly patients: a case report and review article
Authors: Mansour Marah , Abboud Yazan , Bilal Racha , Seilin Nour , Alsuliman Tamim , Mohamed Fawaz K.
Published: March 2022

Background

Small intestine diverticula are rare findings that were mostly reported in the elderly population as asymptomatic findings. However, they can also present with a wide range of symptoms (bloating, early satiety, chronic abdominal discomfort, and diarrhea/steatorrhea) or complications (gastrointestinal bleeding, small bowel obstruction, acute diverticulitis, or perforation) which in turn warrant medical treatment or urgent surgical intervention.

Case presentation

This is a case report of an 84-year-old female who presented with an acute surgical abdomen. An exploratory laparotomy revealed complicated small bowel diverticula with a jejunal diverticulum perforation, for which a diverticulectomy was performed.

Conclusions

Throughout this paper, we are aiming to outweigh the consideration of the possibility of complicated small bowel diverticula as a differential in the evaluation of any acute abdomen, especially in the elderly, which warrants emergency surgical management.
Anterolateral thigh flaps in closing large abdominal wall defect after the resection of mucinous adenocarcinoma: a case report
Authors: Huang Weijia , Lu Hanpeng , Zhang Yu-Xiao , Song Yinghan
Published: March 2022

Background

It is a big challenge to repair a large abdominal wall defect after tumor resection, and en bloc resection with vascularized tissue reconstruction might be an alternative to achieve an improved survival for abdominal wall tumors.

Case presentation

A 45-year-old woman presented with a 1-year history of persistent abdominal pain of the right lower quadrant and a mass with dermal ulceration. An enhanced computed tomography scan and biopsy of the mass were performed to achieve the definite diagnosis of abdominal mucinous adenocarcinoma. After four courses of “FOLFOX” chemotherapy, the tumor grew to 6 × 5 cm during preoperative examination. Thereafter, we removed the tumor and involved tissues and organs and repaired the sizeable abdominal wall defect used by biological meshes and vascularized anterolateral thigh flaps. The patient suffered green drainage of 450 ml in the abdominal cavity and intestinal anastomotic fistula, for which she readmitted and recovered afterward.

Conclusions

Biological mesh combined with vascularized anterolateral thigh flaps could effectively repair the large abdominal wall defect and restore the biological function of the abdominal wall.
Masticatory performance in patients undergoing free fibula flap for mandible reconstruction
Authors: Zhang Jun , Wang Yujing , Yuan Lulu , Wang Weiren
Published: March 2022

Background

To explore the masticatory performance in patients undergoing an osteo(cutaneous) free fibula (OFF) flap for mandible reconstruction by a prospective design.

Methods

A total of 56 patients who had undergone OFF flap reconstructions for mandibular reconstruction secondary to malignant (squamous cell carcinoma) or benign (ameloblastoma) tumor resection were prospectively enrolled. They were asked to complete the masticatory performance test by the weigh method and the chew domain of the University of Washington quality of life questionnaire (version 4) preoperatively and at 3, 6, and 12 months postoperatively. The pair nonparametric test was used to analyze the dynamic change of masticatory performance and subjective chew function.

Results

Fifty-one patients were included for analysis finally. The mean masticatory performance for patients with malignant tumors were 53.4% ± 10.3%, 36.4% ± 10.3%, 42.6% ± 9.6%, 52.8% ± 10.9%, and 53.1% ± 11.8% preoperatively, at 2 weeks, 3 months, 6 months, and 12 months postoperatively, respectively. Compared with the preoperative level, the masticatory performance had a significant reduction immediately after surgery (p < 0.001), followed by a return to the baseline level within three months. A similar trend was noted for those with benign tumors. The mean score of chew domain for patients with malignant tumors were 100 ± 0, 54.3 ± 32.9, 81.4 ± 24.5, and 92.9 ± 17.8 preoperatively, at 3 months, 6 months, and 12 months postoperatively, respectively. Compared with the preoperative level, the subjective chew function was greatly affected within the first three months (p < 0.001), and it gradually recovered to the baseline level in the following nine months. A similar trend was noted in patients with benign tumors.

Conclusions

The masticatory performance and subjective chew function was significantly affected after OFF flap reconstructions in the short term, but both recovered to the preoperative levels within 9–12 months.
Patient and visitor aggression de-escalation training for nurses in a teaching hospital in Cairo, Egypt
Authors: Abozaid Dena Ali , Momen Mohamed , Ezz Nahla Fawzy Abou El , Ahmed Hanaa Abdelhakiem , Al-Tehewy Mahi Mahmoud , El-Setouhy Maged , El-Shinawi Mohamed , Hirshon Jon Mark , Houssinie Moustafa El
Published: March 2022

Background

Workplace violence (WPV) has been recognized as a major occupational hazard worldwide. Healthcare professions are particularly at a higher risk of WPV. Patients and their relatives are commonly the most common perpetrators for WPV against physicians. Trainings on the universal precautions of violence, how to effectively anticipate, recognize and manage potentially violent situation is recommended by OSHA as a part of a written, effective, comprehensive, and interactive WPV prevention program.

Objective

To implement and evaluate the effectiveness of a training session delivered to nurses. The training session aimed to increase nurses’ ability to identify potentially violent situations and to effectively manage these situations in a teaching hospital in Egypt.

Methodology

A total of 99 nurses attended the training sessions. Confidence in coping with aggressive patient scale, along with nurses’ attitudes toward WPV, were used to assess the effectiveness of the training sessions.

Results

Nurses’ perceived confidence to deal with aggression increased after attending the training sessions. Nurses’ attitudes toward WPV positively changed after attending the training session.

Conclusion and recommendations

Increasing awareness of the problem among healthcare professions as well as the public is warranted. Violence prevention program with a zero-tolerance policy is warranted.
Developing sero-diagnostic tests to facilitate Plasmodium vivax Serological Test-and-Treat approaches: modeling the balance between public health impact and overtreatment
Authors: Obadia Thomas , Nekkab Narimane , Robinson Leanne J. , Drakeley Chris , Mueller Ivo , White Michael T.
Published: March 2022

Background

Eliminating Plasmodium vivax will require targeting the hidden liver-stage reservoir of hypnozoites. This necessitates new interventions balancing the benefit of reducing vivax transmission against the risk of over-treating some individuals with drugs which may induce haemolysis. By measuring antibodies to a panel of vivax antigens, a strategy of serological-testing-and-treatment (PvSeroTAT) can identify individuals with recent blood-stage infections who are likely to carry hypnozoites and target them for radical cure. This provides a potential solution to selectively treat the vivax reservoir with 8-aminoquinolines.

Methods

PvSeroTAT can identify likely hypnozoite carriers with ~80% sensitivity and specificity. Diagnostic test sensitivities and specificities ranging 50–100% were incorporated into a mathematical model of vivax transmission to explore how they affect the risks and benefits of different PvSeroTAT strategies involving hypnozoiticidal regimens. Risk was measured as the rate of overtreatment and benefit as reduction of community-level vivax transmission.

Results

Across a wide range of combinations of diagnostic sensitivity and specificity, PvSeroTAT was substantially more effective than bloodstage mass screen and treat strategies and only marginally less effective than mass drug administration. The key test characteristic determining of the benefit of PvSeroTAT strategies is diagnostic sensitivity, with higher values leading to more hypnozoite carriers effectively treated and greater reductions in vivax transmission. The key determinant of risk is diagnostic specificity: higher specificity ensures that a lower proportion of uninfected individuals are unnecessarily treated with primaquine. These relationships are maintained in both moderate and low transmission settings (qPCR prevalence 10% and 2%). Increased treatment efficacy and adherence can partially compensate for lower test performance. Multiple rounds of PvSeroTAT with a lower performing test may lead to similar or higher reductions in vivax transmission than fewer rounds with a higher performing test, albeit with higher rate of overtreatment.

Conclusions

At current performance, PvSeroTAT is predicted to be a safe and efficacious option for targeting the hypnozoite reservoir towards vivax elimination. P. vivax sero-diagnostic tests should aim for both high performance and ease of use in the field. The target product profiles informing such development should thus reflect the trade-offs between impact, overtreatment, and ease of programmatic implementation.
Glutathione S-transferase (GST) and cortisol levels vs. microbiology of the digestive system of sheep during lambing
Authors: Szeligowska Natalia , Cholewińska Paulina , Smoliński Jakub , Wojnarowski Konrad , Pokorny Przemysław , Czyż Katarzyna , Pogoda-Sewerniak Krystyna
Published: March 2022

Background

During parturition, animals exhibit variation in hormone levels, homeostasis disturbance and dysfunction of the immune system as a result of stress. Glutathione S-transferase (GST) is responsible for the occurrence of oxidative stress in the cells. Cortisol is known as the stress hormone, but it is also involved in the metabolism of proteins, carbohydrates and metabolism processes led by adipose tissue. The aim of the this study was to determine how the levels of GST and cortisol change depending on the parity. Additionally, the influence of lambing on the microbiological composition of the digestive system and placenta in Olkuska sheep was investigated.

Methods

Eighteen ewes were selected for the experiment - primiparas (n = 9) and multiparas (n = 9), they were kept in the same environmental conditions, had the same diet and did not show any disease symptoms. Fecal samples were collected individually from each ewe (n = 18) and then bacterial DNA isolation was made, then qPCR analysis for Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria phyla and Lactobacillaceae family bacteria levels was performed. These samples were also used to analyze cortisol levels by ELISA test. In addition, placenta fragments were collected during delivery, and then the GST level from the tissue was tested.

Results

The analysis of the results showed a higher level of cortisol in primiparous sheep than in multiparous ones, as in the case of glutathione transferase. There were differences between both studied groups in the microbiological composition of the digestive system. In primiparous sheep, the levels of the tested microorganisms were significantly lower than in multiparous ones. A similar relationship occurred in the study of the placental microbiome.

Conclusion

The results show that sheep microbiome, cortisol and GST levels are different in primiparas and multiparas. The study conducted may constitute an introduction to further analyzes that would help positively affect the welfare and homeostasis of the female organism.
SARS-CoV-2: tracing the origin, tracking the evolution
Authors: Voskarides Konstantinos
Published: March 2022

The origin of SARS-CoV-2 is uncertain. Findings support a “bat origin” but results are not highly convincing. Studies found evidence that SARS-CoV-2 was around for many years before the pandemic outbreak. Evidence has been published that the progenitor of SARS-CoV-2 already had the capability to bind strongly to the human ACE2 receptor. This may be an indication that many other animal viruses are capable to jump to humans, having already affinity for a human receptor. This is quite worrying since current ecosystems’ collapse brings people to high proximity with animals, increasing probabilities for random viral transitions. On the other hand, future adaptation of SARS-CoV-2 is of great concern. Virus-host interactions are complicated and unfortunately, we still do not have accurate tools for predicting viruses’ future evolution. Viral adaptation is a multifactorial process and probably SARS-CoV-2 will not become soon, as we wish, a harmless infection. However, humanity is currently under the largest vaccination program and it’s of great interest to see if vaccinations will change the evolutionary game against the virus.
Triglyceride-glucose index and common carotid artery intima-media thickness in patients with ischemic stroke
Authors: Miao Mengyuan , Zhou Guo , Bao Anran , Sun Yaming , Du Huaping , Song Liyan , Cao Yongjun , You Shoujiang , Zhong Chongke
Published: March 2022

Background

Triglyceride glucose (TyG) index was recently reported to be associated with an increased risk of the development and recurrence of cardiovascular events, and atherosclerosis is a main speculative mechanism. However, data on the relationship between TyG index and atherosclerosis, especially in the setting of ischemic stroke, is rare. We aimed to explore the association between TyG index and carotid atherosclerosis in patients with ischemic stroke.

Methods

A total of 1523 ischemic stroke patients with TyG index and carotid artery imaging data were enrolled in this analysis. The TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Carotid atherosclerosis was measured by common carotid artery intima-media thickness (cIMT), and abnormal cIMT was defined as a mean cIMT and maximum cIMT value ≥ 1 mm. Multivariable logistic regression models and restricted cubic spline models were used to assess the relationships between TyG index and abnormal cIMT. Risk reclassification and calibration of models with TyG index were analyzed.

Results

The multivariable-adjusted odds ratios (95% CIs) in quartile 4 versus quartile 1 of TyG index were 1.56 (1.06–2.28) for abnormal mean cIMT and 1.46 (1.02–2.08) for abnormal maximum cIMT, respectively. There were linear relationships between TyG index and abnormal mean cIMT (P for linearity = 0.005) and abnormal maximum cIMT (P for linearity = 0.027). In addition, the TyG index provided incremental predictive capacity beyond established risk factors, shown by an increase in net reclassification improvement and integrated discrimination improvement (all P < 0.05).

Conclusions

A higher TyG index was associated with carotid atherosclerosis measured by cIMT in patients with ischemic stroke, suggesting that TyG could be a promising atherosclerotic marker.
Direct cardiac effects of SGLT2 inhibitors
Authors: Chen Sha , Coronel Ruben , Hollmann Markus W. , Weber Nina C. , Zuurbier Coert J.
Published: March 2022

Sodium-glucose-cotransporter 2 inhibitors (SGLT2is) demonstrate large cardiovascular benefit in both diabetic and non-diabetic, acute and chronic heart failure patients. These inhibitors have on-target (SGLT2 inhibition in the kidney) and off-target effects that likely both contribute to the reported cardiovascular benefit. Here we review the literature on direct effects of SGLT2is on various cardiac cells and derive at an unifying working hypothesis. SGLT2is acutely and directly (1) inhibit cardiac sodium transporters and alter ion homeostasis, (2) reduce inflammation and oxidative stress, (3) influence metabolism, and (4) improve cardiac function. We postulate that cardiac benefit modulated by SGLT2i’s can be commonly attributed to their inhibition of sodium-loaders in the plasma membrane (NHE-1, Nav1.5, SGLT) affecting intracellular sodium-homeostasis (the sodium-interactome), thereby providing a unifying view on the various effects reported in separate studies. The SGLT2is effects are most apparent when cells or hearts are subjected to pathological conditions (reactive oxygen species, inflammation, acidosis, hypoxia, high saturated fatty acids, hypertension, hyperglycemia, and heart failure sympathetic stimulation) that are known to prime these plasmalemmal sodium-loaders. In conclusion, the cardiac sodium-interactome provides a unifying testable working hypothesis and a possible, at least partly, explanation to the clinical benefits of SGLT2is observed in the diseased patient.
Fasting blood glucose in a Ghanaian adult is causally affected by malaria parasite load: a mechanistic case study using convergent cross mapping
Authors: Abidha Carol A. , Amoako Yaw Ampem , Nyamekye Richard King , Bedu-Addo George , Grziwotz Florian , Mockenhaupt Frank P. , Telschow Arndt , Danquah Ina
Published: March 2022

Background

Adults with diabetes mellitus (DM) in malaria-endemic areas might be more susceptible to Plasmodium infection than healthy individuals. Herein, the study was aimed at verifying the hypothesis that increased fasting blood glucose (FBG) promotes parasite growth as reflected by increased parasite density.

Methods

Seven adults without DM were recruited in rural Ghana to determine the relationships between FBG and malaria parasite load. Socio-economic data were recorded in questionnaire-based interviews. Over a period of 6 weeks, FBG and Plasmodium sp. Infection were measured in peripheral blood samples photometrically and by polymerase chain reaction (PCR)-assays, respectively. Daily physical activity and weather data were documented via smartphone recording. For the complex natural systems of homeostatic glucose control and Plasmodium sp. life cycle, empirical dynamic modelling was applied.

Results

At baseline, four men and three women (median age, 33 years; interquartile range, 30–48) showed a median FBG of 5.5 (5.1–6.0 mmol/L); one participant had an asymptomatic Plasmodium sp. infection (parasite density: 240/µL). In this participant, convergent cross mapping (CCM) for 34 consecutive days, showed that FBG was causally affected by parasite density (p < 0.02), while the reciprocal relationship was not discernible (p > 0.05). Additionally, daily ambient temperature affected parasite density (p < 0.01).

Conclusion

In this study population living in a malaria-endemic area, time series analyses were successfully piloted for the relationships between FBG and Plasmodium sp. density. Longer observation periods and larger samples are required to confirm these findings and determine the direction of causality.
Liquid biopsy: a step closer to transform diagnosis, prognosis and future of cancer treatments
Authors: Lone Saife N. , Nisar Sabah , Masoodi Tariq , Singh Mayank , Rizwan Arshi , Hashem Sheema , El-Rifai Wael , Bedognetti Davide , Batra Surinder K. , Haris Mohammad , Bhat Ajaz A. , Macha Muzafar A.
Published: March 2022

Over the past decade, invasive techniques for diagnosing and monitoring cancers are slowly being replaced by non-invasive methods such as liquid biopsy. Liquid biopsies have drastically revolutionized the field of clinical oncology, offering ease in tumor sampling, continuous monitoring by repeated sampling, devising personalized therapeutic regimens, and screening for therapeutic resistance. Liquid biopsies consist of isolating tumor-derived entities like circulating tumor cells, circulating tumor DNA, tumor extracellular vesicles, etc., present in the body fluids of patients with cancer, followed by an analysis of genomic and proteomic data contained within them. Methods for isolation and analysis of liquid biopsies have rapidly evolved over the past few years as described in the review, thus providing greater details about tumor characteristics such as tumor progression, tumor staging, heterogeneity, gene mutations, and clonal evolution, etc. Liquid biopsies from cancer patients have opened up newer avenues in detection and continuous monitoring, treatment based on precision medicine, and screening of markers for therapeutic resistance. Though the technology of liquid biopsies is still evolving, its non-invasive nature promises to open new eras in clinical oncology. The purpose of this review is to provide an overview of the current methodologies involved in liquid biopsies and their application in isolating tumor markers for detection, prognosis, and monitoring cancer treatment outcomes.
Cholesterol promotes EGFR-TKIs resistance in NSCLC by inducing EGFR/Src/Erk/SP1 signaling-mediated ERRα re-expression
Authors: Pan Zhenzhen , Wang Kai , Wang Xiniao , Jia Zhirong , Yang Yuqi , Duan Yalei , Huang Lianzhan , Wu Zhuo-Xun , Zhang Jian-ye , Ding Xuansheng
Published: March 2022

Background

The use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) brings remarkable benefits for the survival of patients with advanced NSCLC harboring EGFR mutations. Unfortunately, acquired resistance seems to be inevitable and limits the application of EGFR-TKIs in clinical practice. This study reported a common molecular mechanism sustaining resistance and potential treatment options to overcome EGFR-TKIs resistance.

Methods

EGFR-TKIs resistant NSCLC cells were established and confirmed by MTT assay. Cholesterol content was detected and the promotional function of cholesterol on NSCLC growth was determined in vivo. Then, we identified ERRα expression as the downstream factor of cholesterol-mediated drug resistance. To dissect the regulatory mechanism, we conducted experiments, including immunofluorescence, co-immunoprecipitation, luciferase reporter assay and chromatin immunoprecipitation assay.

Results

Long-term exposure to EGFR-TKIs generate drug resistance with the characteristic of cholesterol accumulation in lipid rafts, which promotes EGFR and Src to interact and lead EGFR/Src/Erk signaling reactivation-mediated SP1 nuclear translocation and ERRα re-expression. Further investigation identifies ERRα as a target gene of SP1. Functionally, re-expression of ERRα sustains cell proliferation by regulating ROS detoxification process. Lovastatin, a drug used to decrease cholesterol level, and XCT790, an inverse agonist of ERRα, overcome gefitinib and osimertinib resistance both in vitro and in vivo.

Conclusions

Our study indicates that cholesterol/EGFR/Src/Erk/SP1 axis-induced ERRα re-expression promotes survival of gefitinib and osimertinib-resistant cancer cells. Besides, we demonstrate the potential of lowing cholesterol and downregulation of ERRα as effective adjuvant treatment of NSCLC.
Positive regulation of ataxia-telangiectasia-mutated protein (ATM) by E2F transcription Factor 1 (E2F-1) in cisplatin-resistant nasopharyngeal carcinoma cells
Authors: Zhou Zun-Yan , Yang Ji-Yuan , Shao Cheng-Ze , Luo Fei , Du Wei
Published: March 2022

Objective

To explore the mechanism of E2F transcription Factor 1 (E2F-1)-mediated ataxia-telangiectasia-mutated protein (ATM) in cisplatin (DDP)-resistant nasopharyngeal carcinoma (NPC).

Methods

E2F-1 and ATM expression was assessed in DDP-resistant NPC cell lines (CNE2/DDP and HNE1/DDP) and parental cells. Then, DDP-resistant NPC cells were transfected with control shRNA (short hairpin RNA) or E2F-1 shRNAs with or without ATM lentiviral activation particles. The half maximal inhibitory concentration (IC50) was evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, and the cell cycle and cell proliferation were measured by flow cytometry and EdU staining, respectively. In addition, the expression of genes and proteins was quantified by quantitative reverse-transcription polymerase chain reaction (qRT–PCR) and western blotting, respectively.

Results

Both E2F-1 and ATM expression in DDP-resistant NPC cells was much higher than that in parental cells. E2F-1 shRNA reduced ATM expression in DDP-resistant NPC cells, but ATM overexpression had no significant effect on E2F-1. ATM overexpression enhanced DDP resistance in DDP-resistant NPC cells with increased IC50 values, which was reversed by E2F-1 inhibition. Meanwhile, ATM overexpression resulted in upregulation of ABCA2 and ABCA5 in DDP-resistant NPC cells, induced elevations in the transition of the cells into S-phase, and increased cell proliferation with enhanced expression of cyclin E1, CDK2, and Ki67, which was reversed by E2F-1 shRNAs.

Conclusion

Downregulation of E2F-1, possibly by regulating ATM, could block the cell cycle in the G1 phase and reduce the proliferation of CNE2/DDP cells, thereby reversing the resistance of human NPC cells to DDP.
Effects of NAD+ precursor supplementation on glucose and lipid metabolism in humans: a meta-analysis
Authors: Zhong Ou , Wang Jinyuan , Tan Yongpeng , Lei Xiaocan , Tang Zhihan
Published: March 2022

Background

This meta-analysis was performed to investigate the effects of nicotinamide adenine dinucleotide (NAD+) precursor supplementation on glucose and lipid metabolism in human body.

Methods

PubMed, Embase, CENTRAL, Web of Science, Scopus databases were searched to collect clinical studies related to the supplement of NAD+ precursor from inception to February 2021. Then the retrieved documents were screened, the content of the documents that met the requirements was extracted. Meta-analysis and quality evaluation was performed detection were performed using RevMan5.4 software. Stata16 software was used to detect publication bias, Egger and Begg methods were mainly used. The main research terms of NAD+ precursors were Nicotinamide Riboside (NR), Nicotinamide Mononucleotide (NMN), Nicotinic Acid (NA), Nicotinamide (NAM). The changes in the levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and fasting blood glucose were mainly concerned.

Results

A total of 40 articles were included in the meta-analysis, with a sample of 14,750 cases, including 7406 cases in the drug group and 7344 cases in the control group. The results of meta-analysis showed that: NAD+ precursor can significantly reduce TG level (SMD = − 0.35, 95% CI (− 0.52, − 0.18), P < 0.0001), and TC (SMD = − 0.33, 95% CI (− 0.51, − 0.14), P = 0.0005), and LDL (SMD = − 0.38, 95% CI (− 0.50, − 0.27), P < 0.00001), increase HDL level (SMD = 0.66, 95% CI (0.56, 0.76), P < 0.00001), and plasma glucose level in the patients (SMD = 0.27, 95% CI (0.12, 0.42), P = 0.0004). Subgroup analysis showed that supplementation of NA had the most significant effect on the levels of TG, TC, LDL, HDL and plasma glucose.

Conclusions

In this study, a meta-analysis based on currently published clinical trials with NAD+ precursors showed that supplementation with NAD+ precursors improved TG, TC, LDL, and HDL levels in humans, but resulted in hyperglycemia, compared with placebo or no treatment. Among them, NA has the most significant effect on improving lipid metabolism. In addition, although NR and NAM supplementation had no significant effect on improving human lipid metabolism, the role of NR and NAM could not be directly denied due to the few relevant studies at present. Based on subgroup analysis, we found that the supplement of NAD+ precursors seems to have little effect on healthy people, but it has a significant beneficial effect on patients with cardiovascular disease and dyslipidemia. Due to the limitation of the number and quality of included studies, the above conclusions need to be verified by more high-quality studies.
Variability of α/β ratios for prostate cancer with the fractionation schedule: caution against using the linear-quadratic model for hypofractionated radiotherapy
Authors: Cui Ming , Gao Xian-Shu , Li Xiaoying , Ma Mingwei , Qi Xin , Shibamoto Yuta
Published: March 2022

Background

Prostate cancer (PCa) is known to be suitable for hypofractionated radiotherapy due to the very low α/β ratio (about 1.5–3 Gy). However, several randomized controlled trials have not shown the superiority of hypofractionated radiotherapy over conventionally fractionated radiotherapy. Besides, in vivo and in vitro experimental results show that the linear-quadratic (LQ) model may not be appropriate for hypofractionated radiotherapy, and we guess it may be due to the influence of fractionation schedules on the α/β ratio. Therefore, this study attempted to estimate the α/β ratio in different fractionation schedules and evaluate the applicability of the LQ model in hypofractionated radiotherapy.

Methods

The maximum likelihood principle in mathematical statistics was used to fit the parameters: α and β values in the tumor control probability (TCP) formula derived from the LQ model. In addition, the fitting results were substituted into the original TCP formula to calculate 5-year biochemical relapse-free survival for further verification.

Results

Information necessary for fitting could be extracted from a total of 23,281 PCa patients. A total of 16,442 PCa patients were grouped according to fractionation schedules. We found that, for patients who received conventionally fractionated radiotherapy, moderately hypofractionated radiotherapy, and stereotactic body radiotherapy, the average α/β ratios were 1.78 Gy (95% CI 1.59–1.98), 3.46 Gy (95% CI 3.27–3.65), and 4.24 Gy (95% CI 4.10–4.39), respectively. Hence, the calculated α/β ratios for PCa tended to become higher when the dose per fraction increased. Among all PCa patients, 14,641 could be grouped according to the risks of PCa in patients receiving radiotherapy with different fractionation schedules. The results showed that as the risk increased, the k (natural logarithm of an effective target cell number) and α values decreased, indicating that the number of effective target cells decreased and the radioresistance increased.

Conclusions

The LQ model appeared to be inappropriate for high doses per fraction owing to α/β ratios tending to become higher when the dose per fraction increased. Therefore, to convert the conventionally fractionated radiation doses to equivalent high doses per fraction using the standard LQ model, a higher α/β ratio should be used for calculation.
Minimally invasive surgery in emergency surgery: a WSES survey
Authors: Ceresoli Marco , Pisano Michele , Abu-Zidan Fikri , Allievi Niccolò , Gurusamy Kurinchi , Biffl Walt L. , Tebala Giovanni D. , Catena Fausto , Ansaloni Luca , Sartelli Massimo , Kluger Yoram , Baiocchi Gianluca ,   WSES MIS working group, Fette Andreas , Hecker Andreas , Litvin Andrey , Forgione Antonello , Leppaniemi Ari , De Simone Belinda , Sakakushev Boris , Palmatier Casey R. , Bendinelli Cino , Damaskos Dimitris , Picetti Edoardo , Tan Edward , Poiasina Elia , Pikoulis Emmanouil , Cicuttin Enrico , Moore Ernest E. , Velmahos George , Fraga Gustavo , Van Goor Harry , Civil Ian , Wani Imtiz , Di Carlo Isidoro , Galante Joseph , Søreide Kjetil , Degrate Luca , Zorcolo Luigi , De Moya Marc , Braga Marco , Cereda Marco , Sugrue Micheal , Chirica Mircea , De Angelis Nicola , Stahel Philip F. , Ivatury Rao , Ten Broek Richard , Di Saverio Salomone , Beka Solomon Gurmu , Magnone Stefano , Cui Yunfeng , Balogh Zsolt J. , Kelly Micheal Dennis , Inaba Kenji ,   WSES MIS consortia, Coccolini Federico
Published: March 2022

Background

The diffusion of minimally invasive surgery in emergency surgery still represents a developing challenge. Evidence about the use of minimally invasive surgery shows its feasibility and safety; however, the diffusion of these techniques is still poor. The aims of the present survey were to explore the diffusion and variations in the use of minimally invasive surgery among surgeons in the emergency setting.

Methods

This is a web-based survey administered to all the WSES members investigating the diffusion of minimally invasive surgery in emergency. The survey investigated personal characteristics of participants, hospital characteristics, personal confidence in the use of minimally invasive surgery in emergency, limitations in the use of it and limitations to prosecute minimally invasive surgery in emergency surgery. Characteristics related to the use of minimally invasive surgery were studied with a multivariate ordinal regression.

Results

The survey collected a total of 415 answers; 42.2% of participants declared a working experience > 15 years and 69.4% of responders worked in tertiary level center or academic hospital. In primary emergencies, only 28,7% of participants declared the use of laparoscopy in more than 50% of times. Personal confidence with minimally invasive techniques was the highest for appendectomy and cholecystectomy. At multivariate ordinal regression, a longer professional experience, the use of laparoscopy in major elective surgery and bariatric surgery expertise were related to a higher use of laparoscopy in emergency surgery.

Conclusions

The survey shows that minimally invasive techniques in emergency surgery are still underutilized. Greater focus should be placed on the development of dedicated training in laparoscopy among emergency surgeons.
Large medial meniscus extrusion and varus are poor prognostic factors of arthroscopic partial meniscectomy for degenerative medial meniscus lesions
Authors: Xu Tao , Xu Liuhai , Li Xinzhi , Zhou You
Published: March 2022

Background

The indications and efficacy after arthroscopic partial meniscectomy (APM) for degenerative medial meniscus lesions (DMMLs) have been controversial. The purpose of this study was to identify predictors of unfavorable clinical and radiologic outcomes after APM for DMMLs and to choose appropriate indications and improve treatment efficacy.

Methods

A total of 86 patients with DMMLs undergoing APM were retrospectively reviewed. The mean follow-up time was 32.1 months. Clinical outcomes (including Lysholm score) and radiographic results (including Kellgren-Lawrence grade (K–L grade: 0/1/2/3/4) were evaluated at preoperative and final follow-up. Preoperative prognostic factors, including gender, age, Body Mass Index (BMI), Hip–Knee–Ankle (HKA), Medial Posterior Tibial Slope (MPTS), Medial Meniscus Extrusion (MME), K–L grade, occupational kneeling, and cartilaginous condition (Outerbridge grade ≤ 2, VS ≥ 3), for relatively unfavorable (fair or poor grade) Lysholm and progression of K–L grade, were investigated by multivariate logistic regression analysis. Receiver operating characteristic curve was used to identify a cutoff point for the extent of medial meniscal extrusion that was associated with the final Lysholm score.

Results

A significantly improved postoperative Lysholm score (84.5 ± 9.7) compared with the preoperative score (63.8 ± 9.3) (P < 0.001), but a progression of K–L grade (20/36/30/0/0–15/27/25/19/0) (P < 0.001). The adverse prognostic factor of Lysholm score was the advancing age (OR 1.109,P = 0.05) and HKA (OR 0.255,P < 0.001). The adverse prognostic factor of K–L grade progression was MME (OR 10.327,P < 0.001). The cutoff point for the relative value of preoperative medial meniscal extrusion associated with relatively unfavorable Lysholm scores was 2.05 mm (Area = 0.8668,Pvalue < 0.0001, Sensitivity = 62.16%, Specificity = 93.88%).

Conclusions

Clinically, varus alignment, large MME, and older age were found to predict a poor prognosis after APM for DMMLs. The preoperative extent of MME can be used as a predictive factor for osteoarthritis in APM. Patients with varus and MME should avoid APM. High tibial osteotomy may be an effective treatment strategy.
MiR-539-3p inhibited chondrogenic differentiation in human adipose stem cells by targeting Sox9
Authors: Qin Feng , Wang Fang , Wang Xiao-Ping , Chen Jie , Zeng Feng-hua , Sun Cui-Lan , Mao Jia-Cuo Peng , Li Chun-Liang
Published: March 2022

Background

Mesenchymal stem cells (MSCs) have emerged as the attractive candidates for cell therapy for cartilage repair in clinical therapy of osteoarthritis (OA). MiR-539-3p was reported to differentially express during chondrogenic differentiation of adipose stem cells (ASCs) by miRNA microarrays. The aim of the study was to investigate the effects and underlying mechanisms of miR-539-3p on chondrogenic differentiation of ASCs.

Methods

Human ASCs (hASCs) were obtained from liposuction and transfected with miR-539-3p mimic or inhibitor. Then, the cells were cultured in chondrogenic differentiation medium including transforming growth factor-β1 (TGF-β1).

Results

Our results found that miR-539-3p was gradually down-regulated during chondrogenic differentiation of hASCs. MiR-539-3p overexpression inhibited TGF-β1-induced chondrogenic differentiation of hASCs, as supported by reducing the gene and protein expression of chondrogenic differentiation markers type II collagen alpha 1 (COL2A1), aggrecan (ACAN), and type II collagen. In contrast, miR-539-3p inhibitor significantly promoted the chondrogenic differentiation of hASCs. Dual luciferase reporter assay demonstrated that Sox9 was a direct target gene of miR-539-3p. The expression of SRY-box transcription factor 9 (Sox9) was up-regulated progressively over time during chondrogenic differentiation of hASCs. Additionally, Sox9 overexpression notably reversed chondrogenic differentiation of hASCs inhibited by miR-539-3p mimic, as demonstrated by the decreased expression of COL2A1, ACAN, and type II collagen.

Conclusions

Altogether, miR-539-3p inhibited chondrogenic differentiation of hASCs by targeting Sox9. MiR-539-3p may have significant clinical applications for use as a targeted therapy of OA.