bluuebunny/crossref_metadata_2025 huggingface dataset:
Knowledge, attitude, and associated factors towards mental illness among residents of Dessie town, northeast, Ethiopia, a cross-sectional study
Authors: Birkie Mengesha , Anbesaw Tamrat
Published: December 2021

Background

Knowledge and attitude towards mental illness are poor and neglected as compared to medical illness. However, there is an increasing burden of mental illness in the community. As per the knowledge of the investigators, studies are scarce and not done in the study area about knowledge and attitudes of mental illness. Therefore, this study aimed to assess the knowledge, attitude, and associated factors towards mental illness among, Dessie town residents.

Methods

A community-based cross-sectional study was conducted in Dessie town, Northeast, Ethiopia from October 27 to November 29/2020. A multi-stage sampling technique was employed. The data were collected from 477 study participants using a standard structured questionnaire, which were Mental Health Knowledge Schedule (MAKS) and Community Attitude to Mental Illness Inventory (CAMI) respectively. Data were entered using Epi-data version 3.1 and, then exported to SPSS version 26 for analyses. Bivariable and Multivariable logistic regression analyses was employed.

Results

From 477 study participants the prevalence of poor knowledge and unfavorable attitude towards mental illness were 55.3% (95% CI: 50.9, 60.0) and 45.1% (95% CI: 40.7,49.5) respectively. Being female [AOR = 1.62 (95% CI:1.06,2.47)], could not read and write [AOR = 6.28 (95% CI: 2.56, 15.39)], lack of information about mental illness [AOR = 5.82 (95% CI: 3.78,8.94)] and unfavorable attitude [AOR =1.73 (95% CI: 1.12,2.66)] were variables found statistical significant with poor knowledge. Whereas, income < 2166 [AOR = 1.64, (95% CI: 1.12, 2.41)], poor social support [AOR = 2.04, (95% CI: 1.13, 3.68)], moderate social support [AOR = 2.44, (95% CI: 1.45, 3.97)] and poor knowledge [AOR = 1.66, (95% CI: 1.13,2.43)] were variables significantly associated with unfavorable attitude toward mental illness.

Conclusion

In this study about half of the community have poor knowledge, and less than half of the participants have an unfavorable attitude to wards mental illness. There are many factors associated with poor knowledge and unfavorable attitudes. This having poor knowledge and unfavorable attitude may cause certain problems like a decrease in health care of a person with mental illness. Therefore, we recommend practice-based awareness in the community regarding mental health problems needs to be addressed.
15-year survivorship analysis of an interspinous device in surgery for single-level lumbar disc herniation
Authors: Cho Yoon Joo , Park Jong-Beom , Chang Dong-Gune , Kim Hong Jin
Published: December 2021

Background

Interspinous devices have been introduced as alternatives to decompression or fusion in surgery for degenerative lumbar diseases. This study aimed to investigate 15-year survivorship and risk factors for reoperation of a Device for Intervertebral Assisted Motion (DIAM) in surgery for 1-level lumbar disc herniation (LDH).

Methods

A total of 94 patients (54 men and 40 women) underwent discectomy and DIAM implantation for 1-level LDH, with a mean follow-up of 12.9 years (range, 6.3–15.3 years). The mean age was 46.2 years (range, 21–65 years). Sixty-two patients underwent DIAM implantation for L4–5, 27 for L5–6, and 5 for L3–4. Reoperations due to any reason associated with DIAM implantation level or adjacent levels were defined as failure and used as the end point of determining survivorship.

Results

During the 15-year follow-up, 8 patients (4 men and 4 women) underwent reoperation due to recurrence of LDH at the DIAM implantation level, a reoperation rate of 8.5%. The mean time to reoperation was 6.5 years (range, 0.8–13.9 years). Kaplan-Meier analysis showed a cumulative survival rate of the DIAM implantation of 97% at 5 years, 93% at 10 years, and 92% at 15 years after surgery; the cumulative reoperation rate of the DIAM implantation was 3% at 5 years, 7% at 10 years, and 8% at 15 years after surgery. Mean survival time was predicted to be 14.5 years (95% CI, 13.97–15.07). The log-rank test and Cox proportional hazard model showed that age, sex, and location did not significantly affect the reoperation rate of DIAM implantation.

Conclusions

Our results showed that DIAM implantation significantly decreased reoperation rate for LDH in the 15-year survivorship analysis. We suggest that DIAM implantation could be considered a useful intermediate step procedure for LDH surgery. To the best of our knowledge, this is the longest follow-up study in which surgical outcomes of interspinous device surgery were reported.
IL-6 and IL-10 gene polymorphisms and cirrhosis of liver risk from a comprehensive analysis
Authors: Zheng Minghui , Fang Weizhen , Yu Menglei , Ding Rui , Zeng Hua , Huang Yan , Mi Yuanyang , Duan Chaohui
Published: December 2021

Background

Different inflammatory and immune cytokines play a key role in the development of cirrhosis of liver (CL). To investigate the association between interleukin-6,10 (IL-6,10) genes polymorphisms and CL risk through comparison of the allele and genotype distribution frequencies by meta-analysis.

Methods

A literature search covered with the PubMed, Embase, Cochrane Library, Web of Science, Google Scholar, SinoMed (CNKI and Wanfang) through 20th April, 2021. Odds ratios (OR) and 95% confidence intervals (CI) were used to assess the strength of associations.

Results

After a comprehensive search, three common polymorphisms (rs1800872, rs1800871, rs1800896) in IL-10 gene were selected, and three common polymorphisms (rs1800795, rs1800796, rs1800797) in IL-6 gene were also identified. The important finding was that IL-10 rs1800872 was a risk factor for CL development. For example, there has a significantly increased relationship between rs1800872 polymorphism and CL both in the whole group (OR: 1.30, 95%CI: 1.01–1.67 in heterozygote model), Asian population (OR: 1.40, 95%CI: 1.03–1.88 in heterozygote model) and hospital-based source of control (OR: 1.40, 95%CI: 1.01–1.96 in dominant model). In addition, significant association was found between rs1800896 and primary biliary cirrhosis subtype disease (OR: 1.30, 95%CI: 1.01–1.68 in allelic contrast model). No association was observed in all three polymorphisms in IL-6 gene.

Conclusion

Our present study suggests that the IL-10 rs1800872 and rs1800896 polymorphisms is potentially associated with the risk of CL susceptibility.
How can learning effects be measured in Balint groups? Validation of a Balint group questionnaire in China
Authors: Fritzsche Kurt , Shi Lili , Löhlein Johanna , Wei Jing , Sha Yue , Xie Yongbiao , He Yanling , Tschuschke Volker , Flatten Guido , Wang Yibo , Jin Chen , Leonhart Rainer
Published: December 2021

Background

Balint groups aim to reflect doctor-patient relationships on the basis of personal cases. This study reports the validation of a questionnaire aimed at the identification of learning processes among Balint group participants in China.

Methods

This multicenter cross-sectional study was conducted during Balint group sessions in Beijing, Guangzhou and Shanghai. A heterogeneous sample of different professional groups was intended to adequately capture the reality of Balint work in China. After a Balint group session, the participants were asked to complete the Mandarin version of the Balint group session questionnaire (BGQ-C) and the group questionnaire (GQ), an internationally validated instrument to assess central dimensions of therapeutic relationships during group processes.

Results

Questionnaires from n = 806 participants from 55 Chinese Balint groups, predominantly comprising individuals with a medical background, were analyzed. Most participants were female (74.6%), and the average age was 34.2 years old (SD = 9.4). The results indicated good to very good reliability (Cronbach’s α = .70 to .86; retest rs = .430 to .697). The verification of the construct validity of the BGQ-C showed satisfying convergent (rs = .465 to .574) and discriminant validity (rs = -.117 to -.209). The model was tested with a confirmatory factor analysis of a three-factor model (standardized root mean square residual = .025; comparative fit index = .977; Tucker-Lewis index = .971). The 3 empirically identified scales resulted in good model fit with the theoretical dimensions of Balint work postulated in the literature: “reflection of transference dynamics in the doctor-patient relationship”, “emotional and cognitive learning” and “case mirroring in the dynamic of the group”. Due to the high correlations between the factors, a single-factor model was possible. A group comparison between the German and Chinese samples showed different loadings across cultures.

Conclusions

The BGQ-C is a quick-to-complete, item-based measuring instrument that allows the relevant dimensions of Balint group work to be recorded. This study suggests good psychometric properties of the Chinese version. Nevertheless, it must be assumed that the composition of constructs in the two countries is different.
Knowledge, attitude, and associated factors towards older people care among nurses working at public hospitals in West Shoa zone, Oromia region, Ethiopia
Authors: Fita Firomsa , Mekonnen Habtamu Sewunet , Endalew Helen Lamesgin , Azagew Abere Woretaw
Published: December 2021

Background

Nurses’ knowledge and attitude regarding the care of older people can have an impact on patient outcomes such as reduced length of hospital stays, reduced readmission rates, and increased patient and family satisfaction. However, evidence is scarce in Ethiopia, particularly in the study area. Therefore, the study aimed to assess the knowledge, attitude, and associated factors towards the care of older people among nurses working at public hospitals in West Shoa Zone, Ethiopia.

Methods

Institutional based cross-sectional study was conducted from April1–30, 2021 among 423 nurses who were working in adult care units. Data were collected through a self-administered questionnaire. The sample was selected using simple random sampling. The logistic regression analysis model was fitted and the Adjusted Odds Ratio at 95% confidence interval was used. P-values less than or equal to 0.05 were considered statistically significant.

Results

A total of 411 nurses participated in the study with a 97.16% response rate. The mean age of the participants was 29.11 (SD ± 3.84) years. The study showed that 37.2% (95% CI: 33, 42%) of the participants had good knowledge and 45.7% (95% CI: 40.9, 50.6%) had a favorable attitude toward the care of older people. The significantly associated factors positively affected both the knowledge and the attitude of nurses. Age greater than 30 years (AOR:2.37, 95% CI: 1.18, 4.75), experience greater than 5 years (3.00: 1.21, 7.41), being BSc degree holder and above (3.57: 1.40, 9.09), lived with older people (2.14: 1.34, 3.42), and nurses working in adult intensive care unit (3.03: 1.03, 8.91) were significantly associated with knowledge. Likewise, being female (2.04: 1.33, 3.12), being BSc degree holder and above (2.77: 1.35, 5.65), lived with older people (1.59: 1.03, 2.44), and care for older people (1.63: 1.06, 2.53) were significantly associated with attitude.

Conclusion

In this study, less than half of the nurses had good knowledge and a favorable attitude towards the care of older people. Continuous professional development regarding the care of older people is important to enhance nurses’ knowledge and attitude.
Reversibility of clinical and computed tomographic lesions mimicking pulmonary fibrosis in a young cat
Authors: Stavri Alba , Masseau Isabelle , Reinero Carol R.
Published: December 2021

Background

In humans with idiopathic pulmonary fibrosis (IPF), specific thoracic computed tomographic (CT) features in the correct clinical context may be used in lieu of histologic examination. Cats develop an IPF-like condition with similar features to humans. As few cats have invasive lung biopsies, CT has appeal as a surrogate diagnostic, showing features consistent with architectural remodeling supporting “end-stage lung”.

Case presentation

A 1-year-old female spayed Domestic Shorthair cat presenting with progressive respiratory clinical signs and thoracic CT changes (reticular pattern, parenchymal bands, subpleural interstitial thickening, pleural fissure thickening, subpleural lines and regions of increased attenuation with traction bronchiectasis and architectural distortion) consistent with reports of IPF was given a grave prognosis for long-term survival. The cat was treated with prednisolone, fenbendazole, pradofloxacin and clindamycin. Five months later, while still receiving an anti-inflammatory dose of prednisolone, the cat was re-evaluated with owner-reported absent respiratory clinical signs. Thoracic CT demonstrated resolution of lung patterns consistent with fibrosis.

Conclusions

Fibrotic lung disease is irreversible. Despite this cat having compatible progressive respiratory signs and associated lung patterns on thoracic CT scan, these abnormalities resolved with non-specific therapy and time, negating the possibility of IPF. While the cause of the distinct CT lesions that ultimately resolved was not determined, infection was suspected. Experimental Toxocara cati infection shows overlapping CT features as this cat and is considered a treatable disease. Improvement of CT lesions months after experimental heartworm-associated respiratory disease in cats has been documented. Reversibility of lesions suggests inflammation rather than fibrosis was the cause of the thoracic CT lesions. This cat serves as a lesson that although thoracic CT has been advocated as a surrogate for histopathology in people with IPF, additional studies in cats are needed to integrate CT findings with signalment, other clinicopathologic features and therapeutic response before providing a diagnosis or prognosis of fibrotic lung disease.
An electrophysiological perspective on Parkinson’s disease: symptomatic pathogenesis and therapeutic approaches
Authors: Lee Lan-Hsin Nancy , Huang Chen-Syuan , Chuang Hsiang-Hao , Lai Hsing-Jung , Yang Cheng-Kai , Yang Ya-Chin , Kuo Chung-Chin
Published: December 2021

Parkinson’s disease (PD), or paralysis agitans, is a common neurodegenerative disease characterized by dopaminergic deprivation in the basal ganglia because of neuronal loss in the substantia nigra pars compacta. Clinically, PD apparently involves both hypokinetic (e.g. akinetic rigidity) and hyperkinetic (e.g. tremor/propulsion) symptoms. The symptomatic pathogenesis, however, has remained elusive. The recent success of deep brain stimulation (DBS) therapy applied to the subthalamic nucleus (STN) or the globus pallidus pars internus indicates that there are essential electrophysiological abnormalities in PD. Consistently, dopamine-deprived STN shows excessive burst discharges. This proves to be a central pathophysiological element causally linked to the locomotor deficits in PD, as maneuvers (such as DBS of different polarities) decreasing and increasing STN burst discharges would decrease and increase the locomotor deficits, respectively. STN bursts are not so autonomous but show a “relay” feature, requiring glutamatergic synaptic inputs from the motor cortex (MC) to develop. In PD, there is an increase in overall MC activities and the corticosubthalamic input is enhanced and contributory to excessive burst discharges in STN. The increase in MC activities may be relevant to the enhanced beta power in local field potentials (LFP) as well as the deranged motor programming at the cortical level in PD. Moreover, MC could not only drive erroneous STN bursts, but also be driven by STN discharges at specific LFP frequencies (~ 4 to 6 Hz) to produce coherent tremulous muscle contractions. In essence, PD may be viewed as a disorder with deranged rhythms in the cortico-subcortical re-entrant loops, manifestly including STN, the major component of the oscillating core, and MC, the origin of the final common descending motor pathways. The configurations of the deranged rhythms may play a determinant role in the symptomatic pathogenesis of PD, and provide insight into the mechanism underlying normal motor control. Therapeutic brain stimulation for PD and relevant disorders should be adaptively exercised with in-depth pathophysiological considerations for each individual patient, and aim at a final normalization of cortical discharge patterns for the best ameliorating effect on the locomotor and even non-motor symptoms.
Client, provider, and visit factors associated with quality in contraceptive counseling in Mexico: an exploratory cross-sectional analysis
Authors: Walker Kay , Prata Ndola , Lahiff Maureen , Quintero Ximena , Holt Kelsey
Published: December 2021

Background

Monitoring clients’ experiences with contraceptive care is vital to inform quality improvement efforts and ensure fulfillment of individuals’ human rights. The Quality of Contraceptive Counseling (QCC) Scale is a previously validated scale that comprehensively measures individuals’ experiences receiving counseling in three subscales: Information Exchange, Interpersonal Relationship, and Disrespect and Abuse. We sought to better understand the correlation of client, provider, and visit factors with client-reported quality of contraceptive counseling in the public sector in two Mexican states using the QCC Scale.

Methods

This cross-sectional survey study used the QCC Scale total score and subscale scores as outcome variables. Explanatory variables included clients’ age, LGBTTTIQ status, relationship status, number of children, education, and occupation; providers’ gender and type of provider; and the reason for visit. Linear and logistic regression models assessed bivariate associations. Multivariable, multilevel mixed-effects models with clinic as a random effect were fit. All models used complete cases (n = 470).

Results

In the multilevel mixed-effects analyses, patients aged 35+ years reported worse Information Exchange (coefficient − 0.29, p = 0.01). Clients receiving care post-partum reported worse Information Exchange (coefficient − 0.25, p = 0.02) and worse total scores (coefficient − 0.15, p = 0.04) compared to clients seeking contraceptive information or methods. Clients who had 1+ children reported better Information Exchange (coefficient 0.21, p = 0.01) than those with no children. Though Disrespect and Abuse subscale scores were overall high (indicating high quality of care), we found a significant association between age and report of such negative experiences: clients in increasing age categories had increasingly higher adjusted odds of reporting no disrespect and abuse (aORs compared to the youngest group were 2.50 for those aged 19–24 years, p = 0.04; 4.53 for those 25–34 years, p = 0.01; and 6.11 for those 35+ years, p = 0.01.)

Conclusions

Our findings align with previous results that younger clients have lower adjusted odds of reporting high-quality services in Mexico. There is a need for continued work supporting youth-friendly services in Mexico, and efforts should aim to ensure zero tolerance for disrespectful or coercive provider behaviors, such as pressuring or scolding clients. Improvements are also needed to ensure quality in counseling for post-partum clients, those aged 35+ years, and those without children.
“Fear of stopping” vs “wanting to get off the medication”: exploring women’s experiences of using domperidone as a galactagogue - a qualitative study
Authors: Zizzo Gabriella , Rumbold Alice R. , Grzeskowiak Luke E.
Published: December 2021

Background

Domperidone is the most frequently prescribed medicine used to increase breast milk supply. There is considerable controversy surrounding the use of domperidone in lactation, due to limited evidence about efficacy and concerns about rare but life-threatening side-effects. Despite this, in many high-income settings such as Australia, use of domperidone among breastfeeding mothers appears to be increasing. The aim of this paper was to explore women’s experiences of using domperidone during breastfeeding.

Methods

Semi-structured interviews were conducted in 2019 with 15 women in Australia who reported using domperidone as a galactagogue during breastfeeding. Interviews were recorded, transcribed and analysed thematically.

Results

Women reported a wide variety of practices concerning the timing of initiation of domperidone use, including prophylactic use, as well as the dose and duration of use. Prolonged periods of use and unsupervised dosing were commonly reported, these practices were sometimes associated with a fear of the consequences of stopping, insufficient provision of information about the drug or feeling dismissed by health professionals. Some women indicated that when doctors refused to prescribe domperidone they responded by doctor shopping and seeking anecdotal information about benefits and risks online, leading to unsupervised practices. Women often reported high expectations surrounding the effectiveness of domperidone, and most used the medication in conjunction with food/herbal galactagogues and non-galactagogue support. Positive outcomes following domperidone use included having greater confidence in breastfeeding and pride at achieving breastfeeding goals.

Conclusions

This study identified a variety of practices concerning domperidone use, including potentially unsafe practices, linked in some cases to inconsistent advice from health professionals and a reliance on online, anecdotal information sources. These findings emphasise the urgent need for development of clinical practice guidelines and a greater focus on translating existing evidence concerning domperidone into clinical practice, including clinical support that is tailored to women’s needs.
Roles of reactive oxygen species, mitochondrial membrane potential, and p53 in evodiamine-induced apoptosis and G2/M arrest of human anaplastic thyroid carcinoma cells
Authors: Chien Chih-Chiang , Wu Ming-Shun , Chou Shih-Wei , Jargalsaikhan Ganbolor , Chen Yen-Chou
Published: December 2021

Background

Our previous studies have shown that evodiamine (EVO) as paclitaxel and nocodazole could trigger apoptosis in various human cancer cells including human renal cell carcinoma cells, colorectal carcinoma cells, and glioblastoma cells. This study aims to investigate the anti-cancer effects of EVO on human anaplastic thyroid carcinoma (ATC) cells, and underlining mechanism.

Methods

Two different endogenous p53 status human anaplastic thyroid carcinoma (ATC) cells including SW1736 (wtp53) and KAT4B (mutp53) were applied in the present study. The cytotoxicity of EVO on ATC cells was measured by MTT assay, and apoptosis and G2/M arrest were detected by propidium iodide (PI) staining followed by flow cytometry. Expression of indicated proteins was evaluated by Western blotting analysis, and pharmacological studies using chemical inhibitors and siRNA were performed for elucidating underlying mechanism. The roles of mitochondrial membrane potential and reactive oxygen species were investigated by flow cytometry using DiOC6 and DCFH-DA dye, respectively.

Results

SW1736 (wtp53) cells showed a higher apoptotic percentage than KAT4B (mutp53) cells in response to EVO stimulation via a flow cytometric analysis. Mechanistic studies showed that increased p53 and its downstream proteins, and disrupted MMP with increased intracellular peroxide production participated in EVO-induced apoptosis and G2/M arrest of SW1736 cells. In EVO-treated KAT4B cells, significant increases in G2/M percentage but little apoptotic events by EVO was observed. Structure-activity analysis showed that an alkyl group at position 14 was critical for induction of apoptosis related to ROS production and MMP disruption in SW1736 cells.

Conclusion

Evidence indicated that the endogenous p53 status affected the sensitivity of ATC cells to EVO-induced apoptosis and G2/M arrest, revealing the potential role of p53 related to increased ROS production and disrupted MMP in the anticancer actions of EVO, and alkylation at position 14 of EVO is a critical substitution for apoptosis of ATC cells.
ZIP10 is a negative determinant for anti-tumor effect of mannose in thyroid cancer by activating phosphate mannose isomerase
Authors: Ma Sharui , Wang Na , Liu Rui , Zhang Rui , Dang Hui , Wang Yubo , Wang Simeng , Zeng Zekun , Ji Meiju , Hou Peng
Published: December 2021

Background

Mannose, a natural hexose existing in daily food, has been demonstrated to preferentially inhibit the progression of tumors with low expression of phosphate mannose isomerase (PMI). However, its function in thyroid cancer still remains elusive.

Methods

MTT, colony formation and flow cytometry assays were performed to determine the response of thyroid cancer cells to mannose. Meanwhile, mouse models of subcutaneous xenograft and primary papillary thyroid cancer were established to determine in vivo anti-tumor activity of mannose. The underlying mechanism of mannose selectively killing thyroid cancer cells was clarified by a series of molecular and biochemical experiments.

Results

Our data demonstrated that mannose selectively suppressed the growth of thyroid cancer cells, and found that enzyme activity of PMI rather than its protein expression was negatively associated with the response of thyroid cancer cells to mannose. Besides, our data showed that zinc ion (Zn2+) chelator TPEN clearly increased the response of mannose-insensitive cells to mannose by inhibiting enzyme activity of PMI, while Zn2+ supplement could effectively reverse this effect. Further studies found that the expression of zinc transport protein ZIP10, which transport Zn2+ from extracellular area into cells, was negatively related to the response of thyroid cancer cells to mannose. Knocking down ZIP10 in mannose-insensitive cells significantly inhibited in vitro and in vivo growth of these cells by decreasing intracellular Zn2+ concentration and enzyme activity of PMI. Moreover, ectopic expression of ZIP10 in mannose-sensitive cells decrease their cellular response to mannose. Mechanistically, mannose exerted its anti-tumor effect by inhibiting cellular glycolysis; however, this effect was highly dependent on expression status of ZIP10.

Conclusion

The present study demonstrate that mannose selectively kills thyroid cancer cells dependent on enzyme activity of PMI rather than its expression, and provide a mechanistic rationale for exploring clinical use of mannose in thyroid cancer therapy.
A link between mitotic defects and mitotic catastrophe: detection and cell fate
Authors: Sazonova Elena V. , Petrichuk Svetlana V. , Kopeina Gelina S. , Zhivotovsky Boris
Published: December 2021

Although the phenomenon of mitotic catastrophe was first described more than 80 years ago, only recently has this term been used to explain a mechanism of cell death linked to delayed mitosis. Several mechanisms have been suggested for mitotic catastrophe development and cell fate. Depending on molecular perturbations, mitotic catastrophe can end in three types of cell death, namely apoptosis, necrosis, or autophagy. Moreover, mitotic catastrophe can be associated with different types of cell aging, the development of which negatively affects tumor elimination and, consequently, reduces the therapeutic effect. The effective triggering of mitotic catastrophe in clinical practice requires induction of DNA damage as well as inhibition of the molecular pathways that regulate cell cycle arrest and DNA repair. Here we discuss various methods to detect mitotic catastrophe, the mechanisms of its development, and the attempts to use this phenomenon in cancer treatment.
Increased Leishmania infantum resistance to miltefosine and amphotericin B after treatment of a dog with miltefosine and allopurinol
Authors: Gonçalves Gustavo , Campos Monique Paiva , Gonçalves Alessandra Silva , Medeiros Lia Carolina Soares , Figueiredo Fabiano Borges
Published: December 2021

Background

Leishmania infantumis the most important etiological agent of visceral leishmaniasis in the Americas and Mediterranean region, and the dog is the main host. Miltefosine was authorized to treat canine leishmaniasis (CanL) in Brazil in 2017, but there is a persistent fear of the emergence of parasites resistant not only to this drug but, through cross-resistance mechanisms, also to meglumine antimoniate and amphotericin B. Additionally, the literature shows that acquisition of resistance is followed by increased parasite fitness, with higher rates of proliferation, infectivity and metacyclogenesis, which are drivers of parasite virulence. In this context, the aim of this study was to analyze the impact of treating a dog with miltefosine and allopurinol on the generation of parasites resistant to miltefosine, amphotericin B and meglumine antimoniate.

Methods

In vitro susceptibility tests were conducted against miltefosine, amphotericin B and meglumine antimoniate with T0 (parasites isolated from a dog before treatment with miltefosine plus allopurinol), T1 (after 1 course of treatment) and T2 (after 2 courses of treatment) isolates. The rates of cell proliferation, infectivity and metacyclogenesis of the isolates were also evaluated.

Results

The results indicate a gradual increase in parasite resistance to miltefosine and amphotericin B with increasing the number of treatment courses. An increasing trend in the metacyclogenesis rate of the parasites was also observed as drug resistance increased.

Conclusion

The data indicates an increasedL. infantumresistance to miltefosine and amphotericin B after the treatment of a dog with miltefosine plus allopurinol. Further studies with a larger number ofL. infantumstrains isolated from dogs with varied immune response profiles and undergoing different treatment regimes, are advocated.

Graphical Abstract
Randomized controlled trial of ragweed sublingual immunotherapy tablet in the subpopulation of Canadian children and adolescents with allergic rhinoconjunctivitis
Authors: Ellis Anne K. , Gagnon Remi , Bernstein David I. , Nolte Hendrik
Published: December 2021

Background

Post hoc analyses of randomized placebo-controlled trials have demonstrated efficacy and tolerability of the ragweed sublingual immunotherapy (SLIT)-tablet in Canadian adults with ragweed pollen-induced allergic rhinitis/conjunctivitis (AR/C). This post hoc analysis evaluated the efficacy and tolerability of the ragweed SLIT-tablet in the subpopulation of Canadian children and adolescents with AR/C in a previously described randomized, double-blind, placebo-controlled trial.

Methods

The trial (NCT02478398) was conducted in North American and European children/adolescents ages 5–17 years with ragweed pollen-induced AR/C with or without asthma (FEV1 ≥ 80% predicted). Participants were randomized to daily ragweed SLIT-tablet (12 Amb a 1-U) or placebo for up to 28 weeks. The primary endpoint was the average total combined score (TCS; sum of rhinoconjunctivitis daily symptom score [DSS] and daily medication score [DMS]) during peak ragweed pollen season (RPS). Key secondary endpoints were TCS during the entire RPS, and DSS and DMS during peak RPS. Post hoc analyses of the primary and key secondary endpoints were conducted in the subpopulation of Canadian participants.

Results

Of the 1025 randomized participants, 246 (SLIT-tablet, n = 116; placebo, n = 130) were in the Canadian subpopulation. In the total study population, relative TCS (95% CI) improvement with ragweed SLIT-tablet versus placebo was − 38.3% (− 46.0%, − 29.7%; least square [LS] mean difference, − 2.73; P < 0.001) during peak RPS. In the Canadian subpopulation, relative TCS improvements with ragweed SLIT-tablet versus placebo were − 40.8% (− 54.5%, − 20.2%; LS mean difference, − 1.59; P = 0.001) during peak RPS and − 36.6% (− 50.2%, − 16.5%; LS mean difference, − 1.36; P = 0.002) during the entire RPS. DSS and DMS during peak RPS in the Canadian subpopulation improved with SLIT-tablet versus placebo by − 30.6% (− 45.2%, − 7.7%; LS mean difference, − 0.94; P = 0.010) and − 77.2% (− 97.5%, − 44.2%; LS mean difference, − 0.66; P = 0.003), respectively. No events of anaphylaxis, airway compromise, intramuscular epinephrine administration, eosinophilic esophagitis, or severe treatment-related systemic allergic reactions were reported in the overall population or Canadian subpopulation.

Conclusion

Efficacy and safety of the ragweed SLIT-tablet in Canadian children/adolescents with ragweed pollen-induced AR/C was consistent with the total study population. The ragweed SLIT-tablet resulted in clinically meaningful improvement in symptoms, decreased symptom-relieving medication use, and was well tolerated in Canadian children/adolescents.

Trial registration: clinicaltrials.gov, NCT02478398. Registered June 23, 2015, https://clinicaltrials.gov/ct2/show/NCT02478398?term=NCT02478398&draw=2&rank=1
Deep neuromuscular block reduces the incidence of intra-operative complications during laparoscopic donor nephrectomy: a pooled analysis of randomized controlled trials
Authors: Reijnders-Boerboom Gabby T. J. A. , van Helden Esmee V. , Minnee Robert C. , Albers Kim I. , Bruintjes Moira H. D. , Dahan Albert , Martini Chris H. , d’Ancona Frank C. H. , Scheffer Gert-Jan , Keijzer Christiaan , Warlé Michiel C.
Published: December 2021

Study objective

To assess whether different intensities of intra-abdominal pressure and deep neuromuscular blockade influence the risk of intra-operative surgical complications during laparoscopic donor nephrectomy.

Design

A pooled analysis of ten previously performed prospective randomized controlled trials.

Setting

Laparoscopic donor nephrectomy performed in four academic hospitals in the Netherlands: Radboudumc, Leiden UMC, Erasmus MC Rotterdam, and Amsterdam UMC.

Patients

Five hundred fifty-six patients undergoing a transperitoneal, fully laparoscopic donor nephrectomy enrolled in ten prospective, randomized controlled trials conducted in the Netherlands from 2001 to 2017.

Interventions

Moderate (tetanic count of four > 1) versus deep (post-tetanic count 1–5) neuromuscular blockade and standard (≥10 mmHg) versus low (<10 mmHg) intra-abdominal pressure.

Measurements

The primary endpoint is the number of intra-operative surgical complications defined as any deviation from the ideal intra-operative course occurring between skin incision and closure with five severity grades, according to ClassIntra. Multiple logistic regression analyses were used to identify predictors of intra- and postoperative complications.

Main results

In 53/556 (9.5%) patients, an intra-operative complication with ClassIntra grade ≥ 2 occurred. Multiple logistic regression analyses showed standard intra-abdominal pressure (OR 0.318, 95% CI 0.118–0.862; p = 0.024) as a predictor of less intra-operative complications and moderate neuromuscular blockade (OR 3.518, 95% CI 1.244–9.948; p = 0.018) as a predictor of more intra-operative complications. Postoperative complications occurred in 31/556 (6.8%), without significant predictors in multiple logistic regression analyses.

Conclusions

Our data indicate that the use of deep neuromuscular blockade could increase safety during laparoscopic donor nephrectomy. Future randomized clinical trials should be performed to confirm this and to pursue whether it also applies to other types of laparoscopic surgery.

Trial registration

Clinicaltrials.gov LEOPARD-2 (NCT02146417), LEOPARD-3 trial (NCT02602964), and RELAX-1 study (NCT02838134), Klop et al. (NTR 3096), Dols et al. 2014 (NTR1433).
Identification of ACOT13 and PTGER2 as novel candidate genes of autosomal dominant polycystic kidney disease through whole exome sequencing
Authors: Du Na , Dong Dan , Sun Luyao , Che Lihe , Li Xiaohua , Liu Yong , Wang Bin
Published: December 2021

Background

Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic kidney disorder. Half of the patients would slowly progress to end-stage renal disease. However, the potential target for ADPKD treatment is still lacking.

Methods

Four ADPKD patients and two healthy family members were included in this study. The peripheral blood samples were obtained and tested by the whole exome sequencing (WES). The autosomal mutations in ADPKD patients were retained as candidate sites. The Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein–protein interaction network (PPI) analyses were performed by clusterProfiler R package. A dataset containing 18 ADPKD patients and three normal samples were downloaded from the Gene Expression Omnibus (GEO) database and analyzed using the limma R package.

Results

A total of six mutant genes were identified based on the dominant genetic pattern and most of them had not been reported to be associated with ADPKD. Furthermore, 19 harmful genes were selected according to the harmfulness of mutation. GO and KEGG enrichment analyses showed that the processes of single-organism cellular process, response to stimulus, plasma membrane, cell periphery, and anion binding as well as cyclic adenosine monophosphate (cAMP) signaling pathway and pathways in cancer were significantly enriched. Through integrating PPI and gene expression analyses, acyl-CoA thioesterase 13 (ACOT13), which has not been reported to be related to ADPKD, and prostaglandin E receptor 2 (PTGER2) were identified as potential genes associated with ADPKD.

Conclusions

Through combination of WES, gene expression, and PPI network analyses, we identified ACOT13 and PTGER2 as potential ADPKD-related genes.
RETRACTED ARTICLE: Extracorporeal membrane oxygenation support for SARS-CoV-2: a multi-centered, prospective, observational study in critically ill 92 patients in Saudi Arabia
Authors: Alhumaid Saad , Al Mutair Abbas , Alghazal Header A. , Alhaddad Ali J. , Al-Helal Hassan , Al Salman Sadiq A. , Alali Jalal , Almahmoud Sana , Alhejy Zulfa M. , Albagshi Ahmad A. , Muhammad Javed , Khan Amjad , Sulaiman Tarek , Al-Mozaini Maha , Dhama Kuldeep , Al-Tawfiq Jaffar A. , Rabaan Ali A.
Published: December 2021

Background

Extracorporeal membrane oxygenation (ECMO) has been used as a rescue strategy in patients with severe with acute respiratory distress syndrome (ARDS) due to SARS-CoV-2 infection, but there has been little evidence of its efficacy.

Objectives

To describe the effect of ECMO rescue therapy on patient-important outcomes in patients with severe SARS-CoV-2.

Methods

A case series study was conducted for the laboratory-confirmed SARS-CoV-2 patients who were admitted to the ICUs of 22 Saudi hospitals, between March 1, 2020, and October 30, 2020, by reviewing patient’s medical records prospectively.

Results

ECMO use was associated with higher in-hospital mortality (40.2% vs. 48.9%; p = 0.000); lower COVID-19 virological cure (41.3% vs 14.1%, p = 0.000); and longer hospitalization (20.2 days vs 29.1 days; p = 0.000), ICU stay (12.6 vs 26 days; p = 0.000) and mechanical ventilation use (14.2 days vs 22.4 days; p = 0.000) compared to non-ECMO group. Also, there was a high number of patients with septic shock (19.6%) and multiple organ failure (10.9%); and more complications occurred at any time during hospitalization [pneumothorax (5% vs 29.3%, p = 0.000), bleeding requiring blood transfusion (7.1% vs 38%, p = 0.000), pulmonary embolism (6.4% vs 15.2%, p = 0.016), and gastrointestinal bleeding (3.3% vs 8.7%, p = 0.017)] in the ECMO group. However, PaO2 was significantly higher in the 72-h post-ECMO initiation group and PCO2 was significantly lower in the 72-h post-ECMO start group than those in the 12-h pre-ECMO group (62.9 vs. 70 mmHg, p = 0.002 and 61.8 vs. 51 mmHg, p = 0.042, respectively).

Conclusion

Following the use of ECMO, the mortality rate of patients and length of ICU and hospital stay were not improved. However, these findings need to be carefully interpreted, as most of our cohort patients were relatively old and had multiple severe comorbidities. Future randomized trials, although challenging to conduct, are highly needed to confirm or dispute reported observations.
Risk factors of asthma in the Asian population: a systematic review and meta-analysis
Authors: Sio Yang Yie , Chew Fook Tim
Published: December 2021

Background and objective

An increasing trend of asthma prevalence was observed in Asia; however, contributions of environmental and host-related risk factors to the development of this disease remain uncertain. This study aimed to perform a systematic review and meta-analysis for asthma-associated risk factors reported in Asia.

Methods

We systematically searched three public databases (Web of Science, PubMed, and Scopus) in Feb 2021. We only included articles that reported environmental and host-related risk factors associated with asthma in the Asian population. Random-effect meta-analyses were conducted for frequently reported asthma-associated risk factors to provide an overall risk estimate of asthma development.

Results

Of 4030 records obtained from public databases, 289 articles were selected for review. The most frequently reported asthma-associated risk factor was the family history of allergy-related conditions. The random-effect asthma risk estimates (pooled odds ratio,OR) were 4.66 (95% confidence interval (CI): 3.73–5.82) for the family history of asthma, 3.50 (95%CI: 2.62–4.67) for the family history of atopy, 3.57 (95%CI: 3.03–4.22) for the family history of any allergic diseases, 1.96 (95%CI: 1.47–2.61) for the family history of allergic rhinitis, and 2.75 (95%CI: 1.12–6.76) for the family history of atopic dermatitis. For housing-related factors, including the presence of mold, mold spots, mold odor, cockroach, water damage, and incense burning, the random-effect pooledORranged from 1.43 to 1.73. Other risk factors with significant pooledORfor asthma development included male gender (1.30, 95%CI: 1.23–1.38), cigarette smoke exposure (1.44, 95%CI: 1.30–1.60), cigarette smoking (1.66, 95%CI: 1.44–1.90), body mass index (BMI)–related parameters (pooledORranged from 1.06 to 2.02), various types of air pollution (NO2, PM10, and O3; pooledORranged from 1.03 to 1.22), and pre- and perinatal factors (low birth weight, preterm birth, and cesarean section; pooledORranged from 1.14 to 1.32).

Conclusions

The family history of asthma was the most frequently reported risk factor for asthma development in Asia with the highest risk estimate for asthma development. This suggests a major role of the genetic component in asthma pathogenesis. Further study on asthma genetics is required to improve the current understanding of asthma etiology.
Elevated LDH greater than 400 U/L portends poorer overall survival in diffuse large B-cell lymphoma patients treated with CD19 CAR-T cell therapy in a real world multi-ethnic cohort
Authors: Rabinovich Emma , Pradhan Kith , Sica R. Alejandro , Bachier-Rodriguez Lizamarie , Mantzaris Ioannis , Kornblum Noah , Shastri Aditi , Gritsman Kira , Goldfinger Mendel , Verma Amit , Braunschweig Ira
Published: December 2021

Anti-CD19 chimeric antigen receptor T-cell therapies have shown striking clinical activity in diffuse large B-cell lymphoma but robust biomarkers predictive of responsiveness are still needed. We treated a multi-ethnic cohort of 31 diffuse large B-cell lymphoma patients with axicabtagene ciloleucel with an overall response rate of 71%. Analysis of various biomarkers identified a significant decrease in overall survival with elevated lactate dehydrogenase, measured both at time of cell infusion and before lymphodepletion. Lactate dehydrogenase was prognostic in a multivariate analysis [HR = 1.47 (1.1–2.0)] and a value of 400 U/L at time of infusion and a value of 440 U/L before lymphodepletion provided the best prognostic cutoffs for overall survival in our cohort. These data demonstrate efficacy of anti-CD19 chimeric antigen receptor T-cell therapy in a diverse inner city population and demonstrate novel lactate dehydrogenase cutoffs as prognostic biomarkers.
Genotypic variation in root morphology, cotton subtending leaf physiology and fiber quality against nitrogen
Authors: ASIF Iqbal , DONG Qiang , WANG Xiangru , GUI Huiping , ZHANG Hengheng , PANG Nianchang , ZHANG Xiling , SONG Meizhen
Published: December 2021

Background

Nitrogen (N) is important for improving various morphological and physiological processes of cotton but their contribution to fiber quality is still lacking.

Aims

The current study aimed to explore the relationship between root morphology, subtending leaf physiology, and fiber quality of contrasting N-efficient cotton genotypes in response to N.

Methods

We analyzed the above parameters of CCRI 69 (N-efficient) and Xinluzao-30 (XLZ-30, N-inefficient) under control (2.5 mmol·L−1) and high N (5 mmol·L−1) conditions.

Results

The results showed that root morphological traits were increased in CCRI-69 under control conditions than high N. Subtending leaf morphology, chlorophyll and carotenoid contents, free amino acids, and soluble proteins were higher under high N as compared with the control. However, soluble sugars, fructose, sucrose contents, and sucrose phosphate synthase were higher under control conditions than high N across the growth stages. Irrespective of the N conditions, all morphological and physiological traits of cotton subtending leaf were higher in CCRI-69 than XLZ-30. Except for fiber uniformity, fiber quality traits like fiber length, strength, micronaire, and elongation were improved under control conditions than high N. Between the genotypes, CCRI-69 had significantly higher fiber length, strength, micronaire, and elongation as compared with XLZ-30. Strong positive correlations were found between root morphology, soluble sugars, sucrose content, and sucrose phosphate synthase activity with fiber quality traits, respectively.

Conclusions

These findings suggest that CCRI-69 performed better in terms of growth and fiber quality under relatively low N condition, which will help to reduce fertilizer use, the cost of production, and environmental pollution.
Interprofessional Internet Consultations: The Potential Benefits and Perils of eConsults
Authors: Kass Joseph S. , Rose Rachel V.
Published: December 2021

This article addresses the question of whether neurologists performing interprofessional internet consultations, known as eConsults, face the same malpractice liability as for face-to-face patient care. Because the physician-patient relationship is usually unambiguous, determining the scope of legal liability arising from these relatively new approaches to patient care requires understanding the types of interactions courts have found to establish a patient-physician relationship.
The Transformation of Documenting and Coding: Evaluation and Management Codes for Outpatient Neurology Services
Authors: Villanueva Raissa , Busis Neil A. , Cohen Bruce H. , Ciccarelli Luana
Published: December 2021

This article discusses the optimal ways to document and code for outpatient evaluation and management (E/M) codes. Since the changes for Current Procedural Terminology (CPT) codes 99202-99215 were finalized for 2021, they have been modified by the Centers for Medicare & Medicaid Services (CMS) in their Medicare Physician Fee Schedule and by technical corrections issued on March 9, 2021. The 21st Century Cures Act mandated that patients can access their notes and test results immediately. These developments have transformed medical documentation and coding for outpatient E/M services. One year in, the authors have a better understanding of the subtleties of documenting and accurately determining levels of service for outpatient encounters using these new rules and regulations, and they share key insights gained by experience with the new system.