bluuebunny/crossref_metadata_2025 huggingface dataset:
The usefulness of noninvasive liver stiffness assessment using shear-wave elastography for predicting liver fibrosis in children
Authors: Lee Seunghyun , Choi Young Hun , Cho Yeon Jin , Lee Seul Bi , Cheon Jung-Eun , Kim Woo Sun , Ko Jae Sung , Koh Jaemoon , Kang Gyeong Hoon
Published: April 2021

Background

Pediatric patients with liver disease require noninvasive monitoring to evaluate the risk of fibrosis progression. This study aimed to identify the significant factors affecting liver stiffness values using two-dimensional shear-wave elastography (2D-SWE), and determine whether liver stiffness can predict the fibrosis stage of various childhood liver diseases.

Methods

This study included 30 children (22 boys and 8 girls; mean age, 5.1 ± 6.1 years; range, 7 days–17.9 years) who had undergone biochemical evaluation, 2D-SWE examination, histopathologic analysis of fibrosis grade (F0 to F3), assessment of necroinflammatory activity, and steatosis grading between August 2016 and March 2020. The liver stiffness from 2D-SWE was compared between fibrosis stages using Kruskal–Wallis analysis. Factors that significantly affected liver stiffness were evaluated using univariate and multivariate linear regression analyses. The diagnostic performance was determined from the area under the receiver operating curve (AUC) values of 2D-SWE liver stiffness.

Results

Liver stiffness at the F0-1, F2, and F3 stages were 7.9, 13.2, and 21.7 kPa, respectively (P < 0.001). Both fibrosis stage and necroinflammatory grade were significantly associated with liver stiffness (P < 0.001 and P = 0.021, respectively). However, in patients with alanine aminotransferase (ALT) levels below 200 IU/L, the only factor affecting liver stiffness was fibrosis stage (P = 0.030). The liver stiffness value could distinguish significant fibrosis (≥ F2) with an AUC of 0.950 (cutoff value, 11.3 kPa) and severe fibrosis (F3 stage) with an AUC of 0.924 (cutoff value, 18.1 kPa). The 2D-SWE values for differentiating significant fibrosis were 10.5 kPa (≥ F2) and 18.1 kPa (F3) in patients with ALT levels below 200 IU/L.

Conclusion

The liver stiffness values on 2D-SWE can be affected by both fibrosis and necroinflammatory grade and can provide excellent diagnostic performance in evaluating the fibrosis stage in various pediatric liver diseases. However, clinicians should be mindful of potential confounders, such as necroinflammatory activity or transaminase level, when performing 2D-SWE measurements for liver fibrosis staging.
A new radiological measurement method used to evaluate the modified transconjunctival orbital fat decompression surgery
Authors: Li Bei , Feng Li , Tang Huamin , Zeng Liuzhi , Lin Wei
Published: April 2021

Purpose

A new radiological method was used to evaluate the plastic effect of modified transconjunctival orbital fat decompression surgery in patients with inactive thyroid-associated ophthalmopathy.

Methods

In this study, 10 inactive patients (14 eyes) with moderate to severe thyroid-associated ophthalmopathy were selected. The patients underwent modified transconjunctival orbital fat decompression surgery. According to the results of a spiral CT scan before and 6 months after the surgery, the INFINITT system workstation was used to measure the eyeball protrusion value. According to the results obtained by the PHLIPS IntelliSpace Portal elliptical area and line segment measurement tools, the standard elliptical vertebral volume formula was used to calculate the muscular cone inner volume. Changes in eyeball protrusion and the inner volume of the muscular cone before and after surgery were examined. Statistical analysis of the correlation between the two parameters was performed.

Results

Radiological measurement results confirmed that removing the orbital fat in the muscle cone during surgery was effective for alleviating eyeball protrusion in patients with thyroid-associated ophthalmopathy (P < 0.05). This surgery caused an obvious change in the muscle cone inner volume (P < 0.05). And there was significant correlation between changes in eyeball protrusion and muscle cone inner volume (r = 0.797, P = 0.0006, P < 0.05).

Conclusion

The radiological assessment method used in this study is simple and easy to implement. For inactive patients with moderate to severe thyroid-associated ophthalmopathy who just want to improve their appearance, the modified orbital fat decompression surgery is worth considering.
Outbreak response operations during the US measles epidemic, 2017–19
Authors: Martin Elena K. , Shearer Matthew P. , Trotochaud Marc , Nuzzo Jennifer B.
Published: April 2021

Background

To understand operational challenges involved with responding to US measles outbreaks in 2017–19 and identify applicable lessons in order to inform preparedness and response operations for future outbreaks, particularly with respect to specific operational barriers and recommendations for outbreak responses among insular communities.

Methods

From August 2019 to January 2020, we conducted 11 telephone interviews with 18 participants representing state and local health departments and community health centers that responded to US measles outbreaks in 2017–19, with a focus on outbreaks among insular communities. We conducted qualitative, thematic coding to identify and characterize key operational challenges and lessons identified by the interviewees.

Results

We categorized principal insights into 5 topic areas: scale of the response, vaccination operations, exclusion policies, community engagement, and countering anti-vaccine efforts. These topics address resource-intensive aspects of these outbreak responses, including personnel demands; guidance needed to support response operations and reduce transmission, such as excluding exposed or at-risk individuals from public spaces; operational challenges and barriers to vaccination and other response activities; and effectively engaging and educating affected populations, particularly with respect to insular and vulnerable communities.

Conclusions

Measles outbreak responses are resource intensive, which can quickly overwhelm existing public health capacities. Early and effective coordination with trusted leaders and organizations in affected communities, including to provide vaccination capacity and facilitate community engagement, can promote efficient response operations. The firsthand experiences of public health and healthcare personnel who responded to measles outbreaks, including among insular communities, provide evidence-based operational lessons that can inform future preparedness and response operations for outbreaks of highly transmissible diseases.
Peer-leaders’ experiences and challenges in distributing HIV self-test kits in a rural fishing community, Rakai, Uganda
Authors: Matovu Joseph K. B. , Nambuusi Aminah , Wanyenze Rhoda K. , Serwadda David
Published: April 2021

Background

Distribution of HIV self-test kits by trained lay people in the community has resulted in increased uptake of HIV testing services among the targeted populations. However, little data exists on the experiences and challenges faced by trained lay people while distributing the kits.

Methods

This qualitative study was conducted in Kasensero fishing community, Rakai, Uganda, in September 2019. We purposely selected 18 out of 34 peer-leaders that participated in a peer-led HIV self-testing intervention to participate in a post-intervention qualitative evaluation. The main intervention included identification and training of lay people in the community (‘peer-leaders’) to distribute HIV self-test kits to pre-selected members of their social network. Data for this study were collected at the end of the intervention. Data were collected on peer-leaders’ experiences in distributing the kits, challenges experienced during distribution and suggestions on how to improve peer-led HIV self-testing in typical fishing communities in the future. Data were analyzed manually following a thematic framework approach.

Results

Of the 18 peer-leaders, eleven (61.1%) were aged 20–24 years while thirteen (72.2%) had secondary education. Most (n = 15) of the peer-leaders reported that they found it easier to distribute the kits to their social network members, with most of them distributing the kits at the social network members’ homes or at their own homes. HIV self-test kits were distributed at varying times (e.g. in the afternoon) depending on the agreement reached between the peer-leader and their social network member. A few peer-leaders reported that some of their social network members initially hesitated to accept the kits while other peer-leaders reported that they spent a ‘lot of time’ explaining the HIV self-testing procedures to some of their illiterate members. Peer-leaders argued for supervised HIV self-testing for illiterate people and the need to continuously follow-up social network members to check if they tested for HIV.

Conclusion

A majority of the peer-leaders successfully distributed the kits to their social network members save for a few who experienced challenges. These findings suggest that lay people can be trained as effective HIV self-test kits distributors to improve the distribution of kits in the community.
Using Z-score to optimize population-specific DDH screening: a retrospective study in Hangzhou, China
Authors: Li Haomin , Shu Liqi , Yu Jin , Xian Zeng , Duan Huilong , Shu Qiang , Ye Jingjing
Published: April 2021

Background

DDH (Developmental Dysplasia of the Hip) screening can potentially avert many morbidities and reduce costs. The debate about universal vs. selective DDH ultrasonography screening in different countries revolves to a large extent around effectiveness, cost, and the possibility of overdiagnosis and overtreatment. In this study, we proposed and evaluated a Z-score enhanced Graf method to optimize population-specific DDH screening.

Methods

A total of 39,710 history ultrasonography hip examinations were collected to establish a sex, side specific and age-based Z-scores model using the local regression method. The correlation between Z-scores and classic Graf types was analyzed. Four thousand two hundred twenty-nine cases with follow-up ultrasonographic examinations and 5284 cases with follow-up X-ray examinations were used to evaluate the false positive rate of the first examination based on the subsequent examinations. The results using classic Graf types and the Z-score enhanced types were compared.

Results

The Z-score enhanced Graf types were highly correlated with the classic Graf’s classification (R = 0.67, p < 0.001). Using the Z-scores ≥2 as a threshold could reduce by 86.56 and 80.44% the false positives in the left and right hips based on the follow-up ultrasonographic examinations, and reduce by 78.99% false-positive cases based on the follow-up X-ray examinations, respectively.

Conclusions

Using an age, sex and side specific Z-scores enhanced Graf’s method can better control the false positive rate in DDH screening among different populations.
Severe erosive lesion of the glenoid in gouty shoulder arthritis: a case report and review of the literature
Authors: Bao Huricha , Qi Yansong , Wei Baogang , Ma Bingxian , Wang Yongxiang , Xu Yongsheng
Published: April 2021

Background

Gout is a metabolic disease characterized by recurrent episodes of acute arthritis. Gout has been reported in many locations but is rarely localized in the shoulder joint. We describe a rare case of gouty arthritis involving bilateral shoulder joints and leading to severe destructive changes in the right shoulder glenoid.

Case presentation

A 62-year-old male was referred for pain and weakness in the right shoulder joint for two years, and the pain had increased in severity over the course of approximately nine months. A clinical examination revealed gout nodules on both feet and elbows. A laboratory examination showed a high erythrocyte sedimentation rate (ESR), high levels of C-reactive protein and hyperuricemia, and an imaging examination showed severe osteolytic destruction of the right shoulder glenoid and posterior humeral head subluxation. In addition, the left humeral head was involved and had a lytic lesion. Because a definite diagnosis could not be made for this patient, a right shoulder biopsy was performed. The pathological examination of the specimen revealed uric acid crystal deposits and granulomatous inflammation surrounding the deposits. After excluding infectious and neoplastic diseases, the patient was finally diagnosed with gouty shoulder arthritis.

Conclusions

Gout affecting the bilateral shoulder joints is exceedingly uncommon, and to our knowledge, severe erosion of the glenoid has not been previously reported. When severe erosion is present, physicians and orthopedic surgeons should consider gouty shoulder arthritis according to previous medical history and clinical manifestations.
Effect of ridge preservation at molar extraction sites with severe periodontitis on the Schneiderian membrane thickness changes: a pilot study
Authors: Wei Yiping , Zhang Bo , Yang Gang , Xu Tao , Hu Wenjie , Chung Kwok-Hung
Published: April 2021

Background

Information regarding the reaction of bone augmentation in terms to sinus mucosa thickness of periodontally compromised molar extraction sites is limited. This retrospective study aimed to analyze the effect of ridge preservation procedures following the extraction of molars with severe periodontitis on the healing pattern of adjacent maxillary sinus mucosal membranes.

Methods

Thirty-one periodontally compromised maxillary molar teeth either receiving ridge preservation (test group, n = 20) or undergoing spontaneous healing (control group, n = 11) were investigated. Cone-beam computed tomography (CBCT) scanning was performed before the extraction procedure and repeated 6 months later. The mucosa thickness (MT) of the adjacent periodontally compromised molar tooth was measured from CBCT images before tooth extraction and after 6 months of healing at nine assigned measurement points. The data were analyzed at α = 0.05.

Results

The prevalence of pre-extraction maxillary sinus mucosal thickening was 60.0% and 63.6% in the test and control groups, respectively. The average MT of the thickened sinus mucosa before tooth extraction was 3.78 ± 2.36 mm in the test group and 4.63 ± 3.20 mm in the control group (P = 0.063). The mean mucosal thickening reductions in the thickened MT subjects after 6 months of healing were 2.20 ± 2.05 mm (test group) and 2.64 ± 2.70 mm (control group), P = 0.289. The differences of MT between the time prior to extraction and after 6 months of healing were statistically significant within both groups (P < 0.05).

Conclusions

Following extraction of molars with severe periodontitis, a reduction in swelling of the Schneiderian membrane has been observed regardless of the addition of a DBBM socket graft. However, a mucosal thickness > 2 mm was still frequently observed.
Online dental teaching practices during the COVID-19 pandemic: a cross-sectional online survey from China
Authors: Jiang Zhiwei , Zhu Danji , Li Jialu , Ren Lingfei , Pu Rui , Yang Guoli
Published: April 2021

Background

Coronavirus disease 2019 (COVID-19) emerged in China in December 2019. The COVID-19 pandemic hindered dental education, as school buildings were closed. Online dental teaching provided an alternative teaching tool for dental education. However, the efficiency of online dental teaching and student preferences for online dental teaching are unclear.

Aim

To investigate the satisfaction with online dental teaching practices among undergraduate dental students and standardized resident physician training students during the COVID-19 pandemic in China.

Methods

A total of 104 undergraduate dental students and 57 standardized resident physician training students from Zhejiang University participated in the study. A 12-item survey was conducted. This investigation included the teaching methods received, frequency of classes, degree of satisfaction, preferred teaching method, whether to participate in a course regarding COVID-19 prevention, and the effects of teaching. The percentages were then calculated and evaluated for each item.

Results

A total of 161 students (104 undergraduate dental students and 57 standardized resident physician training students) participated in this survey. All students had online dental classes during the COVID-19 pandemic. Lecture-based learning (LBL), case-based learning (CBL), problem-based learning (PBL), team-based learning (TBL), and research-based learning (RBL) were selected as teaching methods. Students were more satisfied with LBL and CBL than PBL, RBL, and TBL. The majority of students had more than four classes per week. The most selected protective measures were hand washing, wearing masks, and wearing gloves. A total of 46.6% of students participated in courses on COVID-19. After training, the students consciously chose to wear face shields and protective clothing.

Conclusions

Dental students accepted online dental learning during the COVID-19 pandemic. Students preferred LBL and CBL and were satisfied with the classes. Courses on COVID-19 helped students understand how to prevent COVID-19 transmission in the dental clinic.
Validity and reliability of the Persian version of the nurse spiritual care therapeutics scale (NSCTS)
Authors: Merati-Fashi Fatemeh , Khaledi-Paveh Behnam , Mosafer Hadis , Ebadi Abbas
Published: April 2021

Background

Dealing with the spiritual needs of patients has been recognized as one of the principles of holistic care in nursing. Therefore, it is necessary for nurses to deal with the spiritual issues of patients. Also, a valid and reliable scale is needed to measure nurse-provided spiritual care. So the purpose of this study was to determine the validity and reliability of the Persian version of the “Nurse Spiritual Care Therapeutics Scale” in Iranian nurses.

Method

In a methodological study, English version of the Nurse Spiritual Care Therapeutics Scale was translated into Persian by forward–backward translation procedure. Face validity was assessed by cognitive interview, and content validity was assessed by a panel of experts. In addition, construct validity was assessed by exploratory factor analysis. The participants were 188 nurses working in different adult wards. Reliability was measured using the Cronbach’s alpha and stability reliability was assessed using the internal correlation coefficient (ICC).

Results

In assessing the construct validity, two factors with eigenvalues greater than 1 were identified, which explained 58.47% of the total variance. Cronbach’s alpha value was 0.932, and ICC was 0.892.

Conclusion

As a result, the Persian version of the Nurse Spiritual Care Therapeutics Scale shows a good validity and reliability. Therefore, this scale can be used to evaluate spiritual care at the bedside in Iran.
Pan-dent-emic: safety considerations for dental surgery in the era of COVID-19
Authors: Mascarenhas Roma Enette , Pralhad Swati , Manaktala Nidhi
Published: April 2021

The global coronavirus disease 2019 (COVID-19) pandemic spread has seized the entire world and has created extensive health concerns in the general population. Despite various efforts to prevent the pandemic spread, the flare-up of this disease is still soaring due to the community spread in every area. The droplet spread from the afflicted is of the highest concern because of its rapid spread to uninfected individuals. Dental treatments have to be planned and carried out with extreme caution and dental personnel should take extreme care and follow meticulous guidelines when treating an individual with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection. This article highlights the clinical picture of COVID-19 (coronavirus diseases 2019) and presents a summary of precautionary and prophylactic measures in preventing the cross-infection and the nosocomial spread of the infection in a dental setting.
Prophylactic use of dural tenting sutures in elective craniotomies in adults—is it necessary? A study protocol for a multicentre, investigator- and participant-blinded randomised, parallel-group, non-inferiority trial
Authors: Kunert Przemysław , Przepiórka Łukasz , Fortuniak Jan , Wiśniewski Karol , Bobeff Ernest Jan , Larysz Patrycja , Kruk Rafał , Kulesza Bartłomiej , Szczepanek Dariusz , Ładziński Piotr , Żyłkowski Jarosław , Kujawski Sławomir , Łabędzka Kamila , Jaskólski Dariusz , Rola Radosław , Trojanowski Tomasz , Marchel Andrzej
Published: April 2021

Background

In the early days of neurosurgery, extradural haemorrhages (EDHs) contributed to a high mortality rate after craniotomies. Almost a century ago, Walter Dandy reported dural tenting sutures as an effective way to prevent postoperative EDH. Over time, his technique gained in popularity and significance to finally become a neurosurgical standard. Yet, several retrospective reports and one prospective report have questioned the ongoing need for dural tenting sutures. Dandy’s explanation that the haemostasis observed under hypotensive conditions is deceiving and eventually causes EDH may be obsolete. Today, proper intra- and postoperative care, including maintenance of normovolemia and normotension and the use of modern haemostatic agents, may be sufficient for effective haemostasis. Thus, there is a fundamental need to evaluate the necessity of dural tenting sutures in a solid, unbiased, evidence-based manner.

Methods

This study is designed as a randomised, multicentre, double-blinded, controlled interventional trial with 1:1 allocation. About one half of the participants will undergo craniotomy without dural tenting sutures and will be considered an intervention group. The other half will undergo craniotomy with these sutures. Both groups will be followed clinically and radiologically. The primary outcome is reoperation due to extradural haematoma. Secondary outcomes aim to evaluate the impact of dural tenting sutures on mortality, readmission risk, postoperative headaches, size of extradural collection, cerebrospinal fluid leak risk and the presence of any new neurological deficit. The study protocol follows the SPIRIT 2013 statement.

Discussion

It is possible that many neurosurgeons around the globe are tenting the dura in elective craniotomies which brings no benefit and only extends the operation. Unfortunately, there is not enough data to support or reject this technique in modern neurosurgery. This is the first study that may produce strong, evidence-based recommendations on using dural tenting sutures.

Trial registration, ethics and dissemination

The Bioethics Committee of the Medical University of Warsaw approved the study protocol (KB/106/2018). The trial is registered at http://www.clinicaltrials.gov (NCT03658941) on September 6, 2018. The findings of this trial will be submitted to a peer-reviewed neurosurgical journal. Abstracts will be submitted to relevant national and international conferences.

Trial status

Protocol version and date: version 1.5, 14.01.2020

First recruitment: September 7, 2018

Estimated recruitment completion: September 1, 2021
Determinants of lungworm specificity in five cetacean species in the western Mediterranean
Authors: Pool Rachel , Romero-Rubira Clara , Raga Juan Antonio , Fernández Mercedes , Aznar Francisco Javier
Published: April 2021

Background

Current data about Pseudaliidae show contrasting patterns of host specificity between congeneric species. We investigated how both contact and compatibility between hosts and parasites contributed to the patterns of lungworm infection observed in a community of five species of cetaceans in the western Mediterranean.

Methods

The lungs of 119 striped dolphins Stenella coeruleoalba, 18 bottlenose dolphins Tursiops truncatus, 7 Risso’s dolphins Grampus griseus, 7 long-finned pilot whales Globicephala melas, and 6 common dolphins Delphinus delphis were analysed for lungworms. Parasites were identified by morphology and analysis of ITS2 sequences using both maximum likelihood and Bayesian inference methods. Body length was used as a proxy for lungworm species fitness in different hosts and compared with Kruskal-Wallis tests. Infection parameters were compared between cetacean species using Fisher’s exact tests and Kruskal-Wallis tests. Phylogenetic specificity was explored by collating the overall lungworm species prevalence values in hosts from previous surveys in various localities. To explore the relative importance of vertical and horizontal transmission, Spearman’s rank correlation was used to look for an association between host size and lungworm burden. A Mantel test was used to explore the association between lungworm species similarity and prey overlap using dietary data.

Results

Halocercus delphini had higher infection levels in striped dolphins and common dolphins; Stenurus ovatus had higher infection levels in bottlenose dolphins; and Stenurus globicephalae had higher infection levels in long-finned pilot whales. These results are congruent with findings on a global scale. Morphometric comparison showed that the larger nematodes were found in the same host species that had the highest parasite burden. Lungworms were found in neonatal striped dolphins and a Risso’s dolphin, and there was a weak but significant correlation between host size and parasite burden in striped dolphins and bottlenose dolphins. There was also a weak but significant association between prey overlap and lungworm species similarity.

Conclusions

Data indicate that phylogenetic specificity has an important role in governing host–parasite associations, as indicated by the higher infection levels and larger nematode size in certain hosts. However, diet can also influence infection patterns in these preferred hosts and contribute to less severe infections in other hosts.

Graphical Abstract
In vitro effects of tropisetron and granisetron against Echinococcus granulosus (s.s.) protoscoleces by involvement of calcineurin and calmodulin
Authors: Shiee Mohammad Reza , Kia Eshrat Beigom , Zahabiun Farzaneh , Naderi Mahmood , Motevaseli Elahe , Nekoeian Shahram , Fasihi Harandi Majid , Dehpour Ahmad Reza
Published: April 2021

Background

Cystic echinococcosis (CE) is a disease caused by the larval stage of Echinococcus granulosus sensu lato  (s.l.). The treatment of CE mainly relies on the use of benzimidazoles, which can commonly cause adverse side effects. Therefore, more efficient treatment options are needed. Drug repurposing is a useful approach for advancing drug development. We have evaluated the in vitro protoscolicidal effects of tropisetron and granisetron in E. granulosus sensu stricto (s.s.) and assessed the expression of the calcineurin (CaN) and calmodulin (CaM) genes, both of which have been linked to cellular signaling activities and thus are potentially promising targets for the development of drugs.

Methods

Protoscoleces (PSC) of E. granulosus (s.s.) (genotype G1) obtained from sheep hepatic hydatid cysts were exposed to tropisetron and granisetron at concentrations of 50, 150 and 250 µM for various periods of time up to 10 days. Cyclosporine A (CsA) and albendazole sulfoxide were used for comparison. Changes in the morphology of PSC were investigated by light microscopy and scanning electron microscopy. Gene expression was assessed using real-time PCR at the mRNA level for E. granulosus calcineurin subunit A (Eg-CaN-A), calcineurin subunit B (Eg-CaN-B) and calmodulin (Eg-CaM) after a 24-h exposure at 50 and 250 µM, respectively.

Results

At 150 and 250 µM, tropisetron had the highest protoscolicidal effect, whereas CsA was most effective at 50 µM. Granisetron, however, was less effective than tropisetron at all three concentrations. Examination of morphological alterations revealed that the rate at which PSC were killed increased with increasing rate of PSC evagination, as observed in PSC exposed to tropisetron. Gene expression analysis revealed that tropisetron at 50 μM significantly upregulated Eg-CaN-B and Eg-CaM expression while at 250 μM it significantly downregulated both Eg-CaN-B and Eg-CaM expressions; in comparison, granisetron decreased the expression of all three genes at both concentrations.

Conclusions

Tropisetron exhibited a higher efficacy than granisetron against E. granulosus (s.s.) PSC, which is probably due to the different mechanisms of action of the two drugs. The concentration-dependent effect of tropisetron on calcineurin gene expression might reflect its dual functions, which should stimulate future research into its mechanism of action and evaluation of its potential therapeutical effect in the treatment of CE.

Graphical Abstract
Apoptosis-like cell death upon kinetoplastid induction by compounds isolated from the brown algae Dictyota spiralis
Authors: Chiboub Olfa , Sifaoui Ines , Abderrabba Manef , Mejri Mondher , Fernández José J. , Díaz-Marrero Ana R. , Lorenzo-Morales Jacob , Piñero José E.
Published: April 2021

Background

The in vitro activity of the brown seaweed Dictyota spiralis against both Leishmania amazonensis and Trypanosoma cruzi was evaluated in a previous study. Processing by bio-guided fractionation resulted in the isolation of three active compounds, classified as diterpenes. In the present study, we performed several assays to detect clinical features associated to cell death in L. amazonensis and T. cruzi with the aim to elucidate the mechanism of action of these compounds on parasitic cells.

Methods

The aims of the experiments were to detect and evaluate specific events involved in apoptosis-like cell death in the kinetoplastid, including DNA condensation, accumulation of reactive oxygen species and changes in ATP concentration, cell permeability and mitochondrial membrane potential, respectively, in treated cells.

Results

The results demonstrated that the three isolated diterpenes could inhibit the tested parasites by inducing an apoptosis-like cell death.

Conclusions

These results encourage further investigation on the isolated compounds as potential drug candidates against both L. amazonensis and T. cruzi.

Graphical Abstract
Prevalence of mental health problems and associated factors among front-line public health workers during the COVID-19 pandemic in China: an effort–reward imbalance model-informed study
Authors: Zhang Jing , Wang Yijing , Xu Jingdong , You Hua , Li Yan , Liang Yuan , Li Shan , Ma Lina , Lau Joseph Tak-fai , Hao Yuantao , Chen Shilin , Zeng Jing , Li Jinghua , Gu Jing
Published: April 2021

Background

Poor mental health status and associated risk factors of public health workers have been overlooked during the COVID-19 pandemic. This study used the effort–reward imbalance model to investigate the association between work-stress characteristics (effort, over-commitment, reward) and mental health problems (anxiety and depression) among front-line public health workers during the COVID-19 pandemic in China.

Methods

A total of 4850 valid online questionnaires were collected through a self- constructed sociodemographic questionnaire, the adapted ERI questionnaire, the 9-item Patient Health Questionnaire (PHQ-9) and the 7-item General Anxiety Disorder Scale (GAD-7). Hierarchical logistic regression analysis was conducted to investigate the association between ERI factors and mental health problems (i.e., depression and anxiety), with reward treated as a potential moderator in such associations.

Results

The data showed that effort and over-commitment were positively associated with depression and anxiety, while reward was negatively associated with depression and anxiety. Development and job acceptance were the two dimensions of reward buffered the harmful effect of effort/over-commitment on depression and anxiety, whereas esteem was non-significant.

Conclusions

This study confirmed the harmful effects of effort and over-commitment on mental health among public health workers during the COVID-19 pandemic in China. Such effects could be alleviated through an appropriate reward system, especially the development and job acceptance dimensions of such a system. These findings highlight the importance of establishing an emergency reward system, comprising reasonable work-allocation mechanism, bonuses and honorary titles, a continuous education system and better career-development opportunities.
A phase 1 study of dalpiciclib, a cyclin-dependent kinase 4/6 inhibitor in Chinese patients with advanced breast cancer
Authors: Zhang Pin , Xu Binghe , Gui Lin , Wang Wenna , Xiu Meng , Zhang Xiao , Sun Guilan , Zhu Xiaoyu , Zou Jianjun
Published: April 2021

Background

Dalpiciclib (SHR6390) is a novel inhibitor of cyclin-dependent kinase 4/6 which demonstrated promising anti-tumor potency in preclinical models. This first-in-human study was conducted to evaluate the tolerability, pharmacokinetics, safety, and preliminary antitumor activity of dalpiciclib in patients with advanced breast cancer (ABC).

Methods

In this open-label, phase 1 study, Chinese patients who had failed standard therapy were enrolled to receive oral dalpiciclib in 3 + 3 dose-escalation pattern at doses of 25–175 mg. Eligible patients were given a single-dose of dalpiciclib in week 1, followed by once daily continuous doses for 3 weeks, and 1 week off in 28-day cycles. Based on the tolerability, pharmacokinetics, and activity data revealed from the dose-escalation phase, three dose cohorts were selected to expand to 8–10 patients. The primary endpoints were maximum tolerated dose (MTD) and pharmacokinetics.

Results

Between Apr 15, 2016 and Dec 21, 2018, 40 patients were enrolled; all were diagnosed of hormone receptor-positive and HER2-negative ABC. Dalpiciclib 100 mg, 125 mg, and 150 mg cohorts were expanded to 10 patients. No dose-limiting toxicity was observed and the MTD was not reached. Adverse events (AEs) of grade 3 or 4 were observed in 22 (55.0%) of 40 patients, being neutropenia (52.5%), leukopenia (35.0%), thrombocytopenia (5.0%), and hypertension (2.5%). No serious AEs were reported. At the doses of 50–175 mg, steady state areas under the concentration-time curve and peak concentration increased almost proportionally with dose. The disease control rate (DCR) was 62.5% (25/40, 95% CI: 45.8–77.3). Two patients (5%; 125 mg and 150 mg cohorts) achieved partial response, with responses lasting 169 and 356+ days, respectively. Among the three expansion cohorts, the 150 mg cohort had the numerically highest DCR of 80.0% (95% CI: 44.4–97.5) and longest median progression-free survival of 8.4 months (95% CI: 2.1–not reached).

Conclusions

Dalpiciclib showed acceptable safety profile and dose-dependent plasma exposure in Chinese patients with ABC. The recommended phase 2 dose was 150 mg. Preliminary evidence of clinical activity was observed, which warrants further validation.

Trial registration

ClinicalTrials.gov identifier: NCT02684266. Registered Feb 17, 2016.
“If you have a pain, get on a plane”: qualitatively exploring how short-term Canadian international retirement migrants prepare to manage their health while abroad
Authors: Pickering John , Crooks Valorie A. , Snyder Jeremy , Milner Trudie
Published: April 2021

Background

Every year, tens of thousands of older Canadians travel abroad during the winter months to enjoy warmer destinations that offer social and recreational opportunities. How do these Canadians prepare to manage their health while abroad? In this analysis we explore this question by developing a typology of preparatory strategies.

Methods

Semi-structured interviews were conducted with 19 older Canadians living seasonally in Yuma, Arizona (United States). Interviews were transcribed verbatim and thematically analysed to form the basis of a typology of preparatory strategies.

Results

Four distinct preparatory strategies form the typology that summarizes how Canadian international retirement migrants prepare to manage their health while abroad. First, some participants became thoroughly prepared by gathering information from multiple sources and undertaking specific preparatory activities (e.g., visiting a travel medicine clinic, purchasing travel health insurance, bringing prescription refills). Second, some participants were preparation-adverse and relied on their abilities to address health needs and crises in-the-moment. Third, some participants became well informed about things they could do in advance to protect their health while abroad (e.g., purchasing travel health insurance) but opted not to undertake preparatory actions. A final group of participants prepared haphazardly.

Conclusions

This typology can assist health care providers in international retirement migrant destinations to appreciate differences among this patient population that is often characterized as being relatively homogenous. More research is needed to determine if these preparatory strategies are common in other mobile populations and if they are found in other destinations popular with international retirement migrants.
Formaldehyde exposure and leukemia risk: a comprehensive review and network-based toxicogenomic approach
Authors: Kang Doo Seok , Kim Hyun Soo , Jung Jong-Hyeon , Lee Cheol Min , Ahn Yeon-Soon , Seo Young Rok
Published: April 2021

Formaldehyde is a widely used but highly reactive and toxic chemical. The International Agency for Research on Cancer classifies formaldehyde as a Group 1 carcinogen, based on nasopharyngeal cancer and leukemia studies. However, the correlation between formaldehyde exposure and leukemia incidence is a controversial issue. To understand the association between formaldehyde exposure and leukemia, we explored biological networks based on formaldehyde-related genes retrieved from public and commercial databases. Through the literature-based network approach, we summarized qualitative associations between formaldehyde exposure and leukemia. Our results indicate that oxidative stress-mediated genetic changes induced by formaldehyde could disturb the hematopoietic system, possibly leading to leukemia. Furthermore, we suggested major genes that are thought to be affected by formaldehyde exposure and associated with leukemia development. Our suggestions can be used to complement experimental data for understanding and identifying the leukemogenic mechanism of formaldehyde.
Association of ABCC8 and KCNJ11 gene variants with type 1 diabetes in south Indians
Authors: Reddy Shilpa , Maddhuri Sailaja , Nallari Pratibha , Ananthapur Venkateshwari , Kalyani Srinivas , Krishna Murali , Cherkuri Nirmala , Patibandala Sireesha
Published: April 2021

Background

Type 1 diabetes mellitus (TIDM) is a polygenic disorder with the involvement of several genetic and environmental risk factors. Mutation in genes namely ABCC8 and KCNJ11 disrupt the potentiality of KATP channel and regulates the secretion of insulin by detecting a change in the blood glucose level and consequently maintains glucose homeostasis. The present study was designed to investigate the association of ABCC8 and KCNJ11gene polymorphisms with type 1 diabetes. A case-control study was conducted enrolling 60 cases suffering from T1DM and 60 healthy controls of comparable age and sex. Gene variations were determined by PCR-RFLP and ARMS-PCR method.

Results

The ABCC8-3C > T (rs1799854) variation was found to be significantly associated with T1DM (p<0.01) and “CT” genotype was found to be predominant in T1DM with a threefold increased risk to diabetes and the association was statistically significant. However, we did not find any significant association of C>T (rs1801261) polymorphism of ABCC8 with T1DM. A significant association was observed for genetic variation at rs5219 C>T polymorphism and the frequency of TT genotype was found to be significantly higher in patients (46.7%) than in controls (21.7%), indicating the significant role of the KCNJ11 rs5219 variant in T1DM susceptibility (p<0.001), but we did not observe any significant association of G>A (rs5215) polymorphism of KCNJ11 with T1DM. In addition, haplotype analysis of the two genes revealed four haplotypes such as T-C-G-T, T-C-A-T, C-C-G-T, and T-T-G-T as risk haplotypes for type 1 diabetes (p<0.02) potentially making individual effects of these variants on the disease susceptibility, thereby indicating the synergistic role of these genes in the regulation of glucose homeostasis.

Conclusions

The present study highlights the importance of personalized medicine based on individual genetic profile.
Multivariate optimization of liquid chromatographic conditions for determination of dapagliflozin and saxagliptin, application to an in vitro dissolution and stability studies
Authors: Gurrala Sunitha , Raj Shiva , Subrahmanyam C. V. S. , Anumolu Panikumar D.
Published: April 2021

Background

Analytical quality by design driven HPLC method has been optimized for simultaneous estimation of dapagliflozin and saxagliptin in pharmaceutical dosage form. Response surface methodology was employed for optimization of experimental conditions using three factors such as organic phase (%), pH of aqueous phase, and flow rate of mobile phase.

Results

Virtuous separation of analytes was achieved with mobile phase consisted of acetonitrile: phosphate buffer, pH 5.8 (26:74% v/v) with flow rate 0.96 mL/min using SPOLAR C18 column (250 × 4.6 mm, 5 μ) with run time 6 min and UV detection at 236 nm. Retention time for dapagliflozin and saxagliptin were found to be 3.5 and 5.0 min, respectively. Method was validated as per ICH guidelines. The plot between peak area vs concentration for dapagliflozin and saxagliptin were rectilinear in the range of 0.2-300 μg/mL and 0.1-150 μg/mL respectively with detection and quantification limits were 0.061 and 0.18 μg/mL for dapagliflozin and 0.014 and 0.043 μg/mL for saxagliptin, respectively.

Conclusion

The proposed method was exploited for assay, in vitro dissolution, and stability studies of target drugs in marketed dosage form.
Prevalence of post-traumatic stress symptoms among people influenced by coronavirus disease 2019 outbreak: A meta-analysis
Authors: Qiu Dan , Li Yilu , Li Ling , He Jun , Ouyang Feiyun , Xiao Shuiyuan
Published: April 2021

Background

As one of the most widely researched consequence of traumatic events, the prevalence of post-traumatic stress symptoms among people exposed to the trauma resulting from coronavirus disease 2019 (COVID-19) outbreak varies greatly across studies. This review aimed at examining the pooled prevalence of post-traumatic stress symptoms among people exposed to the trauma resulting from COVID-19 outbreak.

Methods

Systematic searches of databases were conducted for literature published on PubMed, EMBASE, Web of Science, the Cochrane Library, PsycArticle, and Chinese National Knowledge Infrastructure until October 14, 2020. Statistical analyses were performed using R software (PROSPERO registration number: CRD42020180309).

Results

A total of 106,713 people exposed to the trauma resulting from the COVID-19 outbreak were identified in the 76 articles, of which 33,810 were reported with post-traumatic stress symptoms. The pooled prevalence of post-traumatic stress symptoms among people exposed to the trauma resulting from COVID-19 outbreak was 28.34%, with a 95% confidence interval of 23.03-34.32%. Subgroup analysis indicated that older age, male and bigger sample size were associated with higher prevalence of post-traumatic stress symptoms. After controlling for other factors, the results of meta-regression showed that the influence of gender and sample size on prevalence is no longer significant.

Conclusions

Symptoms of post-traumatic stress disorder (PTSD) were very common among people exposed to the trauma resulting from COVID-19 outbreak. Further research is needed to explore more possible risk factors for post-traumatic stress symptoms and identify effective strategies for preventing PTSD-related symptoms among people exposed to the trauma resulting from COVID-19 outbreak.
Characterization of the Action of Tachykinin Signaling on Pulsatile LH Secretion in Male Mice
Authors: Talbi Rajae , Ferrari Kaitlin , Choi Ji Hae , Gerutshang Achi , McCarthy Elizabeth A , Dischino Daniel , León Silvia , Navarro Víctor M
Published: April 2021

The alternation of the stimulatory action of the tachykinin neurokinin B (NKB) and the inhibitory action of dynorphin within arcuate (ARH) Kiss1 neurons has been proposed as the mechanism behind the generation of gonadotropin-releasing hormone (GnRH) pulses through the pulsatile release of kisspeptin. However, we have recently documented that GnRH pulses still exist in gonadectomized mice in the absence of tachykinin signaling. Here, we document an increase in basal frequency and amplitude of luteinizing hormone (LH) pulses in intact male mice deficient in substance P, neurokinin A (NKA) signaling (Tac1KO), and NKB signaling (Tac2KO and Tacr3KO). Moreover, we offer evidence that a single bolus of the NKB receptor agonist senktide to gonad-intact wild-type males increases the basal release of LH without changing its frequency. Altogether, these data support the dispensable role of the individual tachykinin systems in the generation of LH pulses. Moreover, the increased activity of the GnRH pulse generator in intact KO male mice suggests the existence of compensation by additional mechanisms in the generation of kisspeptin/GnRH pulses.
Measuring Race and Ancestry in the Age of Genetic Testing
Authors: Johfre Sasha Shen , Saperstein Aliya , Hollenbach Jill A.
Published: April 2021

Will the rise of genetic ancestry tests (GATs) change how Americans respond to questions about race and ancestry on censuses and surveys? To provide an answer, we draw on a unique study of more than 100,000 U.S. adults that inquired about respondents' race, ancestry, and genealogical knowledge. We find that people in our sample who have taken a GAT, compared with those who have not, are more likely to self-identify as multiracial and are particularly likely to select three or more races. This difference in multiple-race reporting stems from three factors: (1) people who identify as multiracial are more likely to take GATs; (2) GAT takers are more likely to report multiple regions of ancestral origin; and (3) GAT takers more frequently translate reported ancestral diversity into multiracial self-identification. Our results imply that Americans will select three or more races at higher rates in future demographic data collection, with marked increases in multiple-race reporting among middle-aged adults. We also present experimental evidence that asking questions about ancestry before racial identification moderates some of these GAT-linked reporting differences. Demographers should consider how the meaning of U.S. race data may be changing as more Americans are exposed to information from GATs.
Contribution of Genomics to the Surgical Management and Study of Oral Cancer
Authors: Saidak Zuzana , Lailler Claire , Testelin Sylvie , Chauffert Bruno , Clatot Florian , Galmiche Antoine
Published: April 2021

Background

Oral squamous cell carcinoma (OSCC) is the most frequent type of tumor arising from the oral cavity. Surgery is the cornerstone of the treatment of these cancers. Tumor biology has long been overlooked as an important contributor to the outcome of surgical procedures, but recent studies are challenging this concept. Molecular analyses of tumor DNA or RNA provide a rich source of information about the biology of OSCC.

Methods

We searched for relevant articles using PubMed. We examined in particular the prospect of applying molecular methods for minimally invasive exploration of OSCC biology.

Results

We examined five potential applications of genomics to the surgical management and study of OSCC: i) assessing oral potentially malignant lesions; ii) tumor staging prior to surgery; iii) predicting postoperative risk in locally advanced tumors; iv) measuring minimal residual disease and optimizing the longitudinal monitoring of OSCC; and v) predicting the efficacy of medical treatment.

Conclusions

Genomic information can be harnessed in order to identify new biomarkers that could improve the staging, choice of therapy and management of OSCC. The identification of new biomarkers is awaited for better personalization of the surgical treatment of OSCC.