bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypernatremia and hypokalemia with Entrectinib therapy: A case of possible nephrogenic diabetes insipidus
Authors: Fadel Remy , Tabbara Jad , Huml Anne , Nakhoul Georges , Mehdi Ali
Published: January 2023

Introduction:

Hypernatremia and hypokalemia have been reported with the use of Tropomyosin Receptor Kinase Inhibitors (TRKI) but the pathophysiology is not clear. We hereby describe a 72-year-old male with metastatic papillary thyroid carcinoma presenting with hypernatremia and hypokalemia after starting Entrectinib therapy.

Case description:

A 72-year-old male with metastatic papillary thyroid carcinoma was admitted to the hospital for failure to thrive and worsening mental status 6 weeks after starting Entrectinib therapy. He was found to have hypernatremia at 154 mmol/L and hypokalemia at 2.9 mmol/L. Serum and urine osmolalities were 320 and 293 mOsm/kg, respectively with an elevated 24 h urinary potassium of 132 mmol. Polydipsia and polyuria were reported raising the suspicion for underlying diabetes insipidus (DI). Twenty-four hour urine output was around 4.5 L. A DDAVP challenge was performed with no change in hourly urine output and a trivial change in urine osmolality toward 339 mOsm/kg indicating a possible partial nephrogenic DI. Potassium was supplemented and patient was treated with free water enterally and parenterally while stopping Entrectinib therapy. One week later, a water deprivation test failed to elicit a hypernatremic response. Unfortunately, urine osmolality variations with water deprivation were not checked but urine volumes dropped significantly suggesting resolution of presumed nephrogenic DI.

Conclusion:

Hypernatremia has been reported with Tyrosine Kinase Inhibitors but no pathophysiology has been proposed. Hypokalemia however has not been reported. This case reports hypokalemia and hypernatremia in association with Entrectinib therapy with renal potassium wasting and partial nephrogenic as possible pathophysiologic bases respectively. These pathologies seem to be reversible with drug cessation. With the growing use of targeted therapies in oncology and beyond, it seems prudent to better understand the unique electrolyte and water balance abnormalities that might occur so that patients can be counseled and managed appropriately.
Total Talus Replacements
Authors: Jennison Toby , Dalgleish James , Sharpe Ian , Davies Mark , Goldberg Andrew
Published: January 2023

Background:

Total talus replacements are a surgical treatment for talar avascular necrosis (AVN) replacing the entire talus. The potential for total talus replacements has increased with the advent of patient-specific implants using 3D printing based on computed tomographic scanning of the ipsilateral or contralateral talus. The primary aim of this review is to summarize the literature on total talus replacements, providing a historical survey, indications, controversies, complications, survival, and functional outcomes.

Methods:

A systematic review was performed. Articles with survival of total talus replacements were included. Basic percentages and a critical review of the literature was performed.

Results:

Nine articles with 115 patients were included. The mean age ranged from 27.6 to 72 years, but with 5 studies having a mean age of <50 years. Mean follow-up ranged from 12.8 to 152 months. The most common indication was avascular necrosis in 67 patients (58%). Five studies used customized implants and 4 studies used 3D printing. Four studies used ceramic prostheses, 3 cobalt chromium, 1 stainless steel, and 1 titanium with ceramic surface. Three studies involved a talus replacement in conjunction with an ankle replacement. Postoperative complications ranged from 0% to 33%. Of 24 functional outcomes scores, 66.7% demonstrated significant improvement.

Conclusion:

Total talus replacements are a promising alternative to tibiotalocalcaneal fusion for patients with avascular necrosis of the talus; however, further studies are required to ensure reliable outcomes prior to widespread adoption of this technology.

Level of Evidence:

Level IV, review of case series.
Combined toxic effects of T-2 toxin and propiconazole on the early life stages of zebrafish (Danio rerio)
Authors: Zhang Shuai , Liu Xuan , Lv Lu , Liu Chuande , Luo Ting , Zhu Hongmei , Zhang Jinjie , Wang Yanhua
Published: January 2023

Background

Agricultural products are frequently co-contaminated by mycotoxins and pesticides. Most studies have only focused on the single toxicities of these chemicals, while their combined effects are neglected. Therefore, we investigated the combined toxic effects of T-2 toxin (T-2) and propiconazole (PRO) on zebrafish (Danio rerio).

Results

Our data exhibited that T-2 had higher toxicity to embryonic fish (96-h LC50 value of 0.39 mg a.i. L−1) than PRO (96-h LC50 value of 17.16 mg a.i. L−1). The mixture of T-2 and PRO showed an acute synergistic effect on zebrafish. Meanwhile, indicators associated with oxidative stress (SOD, Mn-sod, and cat) displayed significant variations in most exposures to T-2 and PRO mixtures (MTP) compared with the single exposures. The expressions of apoptosis-related genes cas3 and cas9 were also substantially elevated in the high-dose MTP exposure compared with the corresponding T-2 exposure. Besides, the expressions of endocrine system-related genes (TRβ, tsh, crh, cyp19a, and vtg1) were markedly varied in most MTP exposures compared with the corresponding single exposures. Our present results suggested that the mixture of T-2 and PRO could cause enormous effects on oxidative stress, cellular apoptosis, and the hypothalamic–pituitary–thyroid/hypothalamic–pituitary–gonadal (HPG/HPT) axis of zebrafish.

Conclusions

Our results provided new insights into the development of combined pollution standards for agricultural products. Taken together, the impact of the combined effects could be considered and regulated as priorities.
DeepSelectNet: deep neural network based selective sequencing for oxford nanopore sequencing
Authors: Senanayake Anjana , Gamaarachchi Hasindu , Herath Damayanthi , Ragel Roshan
Published: January 2023

Background

Nanopore sequencing allows selective sequencing, the ability to programmatically reject unwanted reads in a sample. Selective sequencing has many present and future applications in genomics research and the classification of species from a pool of species is an example. Existing methods for selective sequencing for species classification are still immature and the accuracy highly varies depending on the datasets. For the five datasets we tested, the accuracy of existing methods varied in the range of $$\sim$$
∼
 77 to 97% (average accuracy < 89%). Here we present DeepSelectNet, an accurate deep-learning-based method that can directly classify nanopore current signals belonging to a particular species. DeepSelectNet utilizes novel data preprocessing techniques and improved neural network architecture for regularization.

Results

For the five datasets tested, DeepSelectNet’s accuracy varied between $$\sim$$
∼
 91 and 99% (average accuracy $$\sim$$
∼
 95%). At its best performance, DeepSelectNet achieved a nearly 12% accuracy increase compared to its deep learning-based predecessor SquiggleNet. Furthermore, precision and recall evaluated for DeepSelectNet on average were always > 89% (average $$\sim$$
∼
 95%). In terms of execution performance, DeepSelectNet outperformed SquiggleNet by $$\sim$$
∼
 13% on average. Thus, DeepSelectNet is a practically viable method to improve the effectiveness of selective sequencing.

Conclusions

Compared to base alignment and deep learning predecessors, DeepSelectNet can significantly improve the accuracy to enable real-time species classification using selective sequencing. The source code of DeepSelectNet is available at https://github.com/AnjanaSenanayake/DeepSelectNet.
Characterization of the REVEILLE family in Rosaceae and role of PbLHY in flowering time regulation
Authors: Liu Zhe , Zhu Xiaoxuan , Liu Weijuan , Qi Kaijie , Xie Zhihua , Zhang Shaoling , Wu Juyou , Wang Peng
Published: January 2023

Background

The circadian clock integrates endogenous and exogenous signals and regulates various physiological processes in plants. REVEILLE (RVE) proteins play critical roles in circadian clock system, especially CCA1 (CIRCADIAN CLOCK ASSOCIATED 1) and LHY (LATE ELONGATED HYPOCOTYL), which also participate in flowering regulation. However, little is known about the evolution and function of the RVE family in Rosaceae species, especially in Pyrus bretschneideri.

Results

In this study, we performed a genome-wide analysis and identified 51 RVE genes in seven Rosaceae species. The RVE family members were classified into two groups based on phylogenetic analysis. Dispersed duplication events and purifying selection were the main drivers of evolution in the RVE family. Moreover, the expression patterns of ten PbRVE genes were diverse in P. bretschneideri tissues. All PbRVE genes showed diurnal rhythms under light/dark cycles in P. bretschneideri leaves. Four PbRVE genes also displayed robust rhythms under constant light conditions. PbLHY, the gene with the highest homology to AtCCA1 and AtLHY in P. bretschneideri, is localized in the nucleus. Ectopic overexpression of PbLHY in Arabidopsis delayed flowering time and repressed the expression of flowering time-related genes.

Conclusion

These results contribute to improving the understanding and functional research of RVE genes in P. bretschneideri.
Whole genome sequencing revealed genetic diversity, population structure, and selective signature of Panou Tibetan sheep
Authors: Shi Huibin , Li Taotao , Su Manchun , Wang Huihui , Li Qiao , Lang Xia , Ma Youji
Published: January 2023

Background

The detection of selective traits in different populations can not only reveal current mechanisms of artificial selection for breeding, but also provide new insights into phenotypic variation in new varieties and the search for genes associated with important traits. Panou sheep is a cultivated breed of Tibetan sheep in China with stable genetic performance, consistent appearance and fast growth and development after decades of artificial selection and cultivation. Due to long-term adaptation to the high altitude, cold and hypoxic environment in the plateau area, they may have formed a unique gene pool that is different from other Tibetan sheep breeds. To explore the genetic resources of Panou sheep, we used next-generation sequencing technology for the first time to investigate the genome-wide population structure, genetic diversity, and candidate signatures of positive selection in Panou sheep.

Results

Comparative genomic analysis with the closely related species Oula sheep (a native breed of Tibetan sheep in China) was used to screen the population selection signal of Panou sheep. Principal component analysis and neighbor joining tree showed that Panou sheep and Oula sheep had differences in population differentiation. Furthermore, analyses of population structure, they came from the same ancestor, and when K = 2, the two populations could be distinguished. Panou sheep exhibit genetic diversity comparable to Oula sheep, as shown by observed heterozygosity, expected heterozygosity and runs of homozygosity. Genome-wide scanning using the Fst and π ratio methods revealed a list of potentially selected related genes in Panou sheep compared to Oula sheep, including histone deacetylase 9 (HDAC9), protein tyrosine kinase 2 (PTK2), microphthalmia-related transcription factor (MITF), vesicular amine transporter 1 (VAT1), trichohyalin-like 1 (TCHHL1), amine oxidase, copper containing 3 (AOC3), interferon-inducible protein 35 (IFI35).

Conclusions

The results suggest that traits related to growth and development and plateau adaptation may be selection targets for the domestication and breeding improvement of Tibetan sheep. This study provides the fundamental footprints for Panou sheep breeding and management.
Significantly different results in the ocular surface microbiome detected by tear paper and conjunctival swab
Authors: Chen Zhangling , Xiang Zhaoyu , Cui Lipu , Qin Xinran , Chen Shuli , Jin Huiyi , Zou Haidong
Published: January 2023

Background

Great variation has been observed in the composition of the normal microbiota of the ocular surface, and therefore, in addition to differences in detection techniques, the method of collecting ocular surface specimens has a significant impact on the test results.The goal of this study is to ascertain whether the eye surface microbial communities detected by two different sampling methods are consistent and hence explore the feasibility of using tear test paper instead of conjunctival swabs to collect eye surface samples for microbial investigation.

Materials and methods

From July 15, 2021, to July 30, 2021, nonirritating tear test strips and conjunctival swabs of both eyes were used in 158 elderly people (> 60 years old) (79 diabetic and 79 nondiabetic adults) in Xinjing Community for high-throughput sequencing of the V3-V4 region of the 16S rRNA gene. The composition of the microbial communities in tear test paper and conjunctival swab samples was analyzed.

Results

There was no statistically significant difference in Alpha diversity of ocular surface microorganisms represented by tear strip and conjunctival swab in diabetic group (P > 0.05), but there was statistically significant difference in Alpha diversity of ocular surface microorganisms detected by tear strip and conjunctival swab in nondiabetic group (P < 0.05). There were statistically significant differences in Beta diversity of ocular surface microorganisms detected by two sampling methods between diabetic group and nondiabetic group (P < 0.05). There were statistically significant differences in ocular surface microorganisms detected by tear strip method between diabetic group and nondiabetic group (P < 0.05), but there was no statistically significant difference in conjunctival swab method (P > 0.05).

Conclusions

Tear test paper and conjunctival swabs detect different compositions of microbes through two different techniques of eye surface microbe sampling. Tear test paper cannot completely replace conjunctival swab specimens for the study of microbes related to eye surface diseases.
In vitro gut microbiome response to carbohydrate supplementation is acutely affected by a sudden change in diet
Authors: Pantoja-Feliciano Ida Gisela , Karl J. Philip , Perisin Matthew , Doherty Laurel A. , McClung Holly L. , Armstrong Nicholes J. , Renberg Rebecca , Racicot Kenneth , Branck Tobyn , Arcidiacono Steve , Soares Jason W.
Published: January 2023

Background

Interactions between diet, stress and the gut microbiome are of interest as a means to modulate health and performance. Here, in vitro fermentation was used to explore the effects of a sudden change in diet, 21 days sole sustenance on the Meal, Ready-to-Eat (MRE) U.S. military combat ration, on inter-species competition and functional potential of the human gut microbiota. Human fecal samples collected before and after MRE intervention or consuming a habitual diet (HAB) were introduced to nutrient-rich media supplemented with starch for in vitro fermentation under ascending colon conditions. 16S rRNA amplicon and Whole-metagenome sequencing (WMS) were used to measure community composition and functional potential. Specific statistical analyses were implemented to detect changes in relative abundance from taxa, genes and pathways.

Results

Differential changes in relative abundance of 11 taxa, Dorea, Lachnospira, Bacteroides fragilis, Akkermansia muciniphila, Bifidobacterium adolescentis, Betaproteobacteria, Enterobacteriaceae, Bacteroides egerthii, Ruminococcus bromii, Prevotella, and Slackia, and nine Carbohydrate-Active Enzymes, specifically GH13_14, over the 24 h fermentation were observed as a function of the diet intervention and correlated to specific taxa of interest.

Conclusions

These findings suggest that consuming MRE for 21 days acutely effects changes in gut microbiota structure in response to carbohydrate but may induce alterations in metabolic capacity. Additionally, these findings demonstrate the potential of starch as a candidate supplemental strategy to functionally modulate specific gut commensals during stress-induced states.
Construction of the Armenian Surname List (ASL) for public health research
Authors: Movsisyan Ani S. , Nasseri Kiumarss , Keegan Theresa H.
Published: January 2023

Background

There are an estimated 460,000 Armenians in the United States, and more than half live in California. Armenian-Americans are generally represented within the ‘White’ or ‘Some Other Race’ race categories in population-based research studies. While Armenians have been included in studies focused on Middle-Eastern populations, there are no studies focused exclusively on Armenians due to a lack of standardized collection of Armenian ethnicity in the United States or an Armenian surname list. To fill this research gap, we sought to construct and evaluate an Armenian Surname List (ASL) for use as an identification tool in public health and epidemiological research studies focused on Armenian populations.

Methods

Data sources for the ASL included the California Public Use Death Files (CPUDF) and the Middle Eastern Surname List (MESL). For evaluation of the ASL, the California Cancer Registry (CCR) database was queried for surnames with birthplace in Armenia and identified by the MESL.

Results

There are a total of 3,428 surnames in the ASL. Nearly half (1,678) of surnames in the ASL were not identified by the MESL. The ASL captured 310 additional Armenian surnames in the CCR than the MESL.

Conclusions

The ASL is the first surname list for identifying Armenians in major databases for epidemiological research.
Subarachnoid extension and unfavorable outcomes in patients with supratentorial intracerebral hemorrhage
Authors: Wang Jinjin , Wang Dandan , Bian Liheng , Wang Anxin , Zhang Xiaoli , Jiang Ruixuan , Wang Wenjuan , Ju Yi , Lu Jingjing , Zhao Xingquan
Published: January 2023

Objective

Our study aimed to investigate the association between the subarachnoid extension of intracranial hemorrhage (SAHE) and clinical outcomes in patients with supratentorial intracerebral hemorrhage (ICH).

Methods

We analyzed the data from a prospective, multi-center, and registry-based database. Two experienced investigators independently assessed ICH imaging data. We compared baseline characteristics and follow-up outcomes. Multivariable logistic regression analysis was used to evaluate the association between SAHE and poor clinical outcomes. We also performed Kaplan–Meier curves and Cox proportional hazards regression analyses to analyze whether SAHE was relevant to a higher mortality rate.

Results

A total of 931 patients were included in this study (SAHE vs. no SAHE, 121 [13.0%] vs. 810 [87.0%]). Patients with SAHE had more severe neurological deficits, higher scores of the mRS, and more remarkable mortality rates at follow-up (allpvalues < 0.05). In multivariable-adjusted models, SAHE was independently associated with a higher risk of poor outcomes (adjusted OR [95%CI]: 2.030 [1.142–3.608] at 3 months; 2.348 [1.337–4.123] at 1 year). In addition, SAHE remained an independent association with an increased death rate at 1 year (adjusted HR [95%CI], 1.314[1.057–1.635]). In the subgroup analysis, the correlation between SAHE and prognosis exists in patients with lobar or deep ICH.

Conclusions

SAHE is independently associated with poor outcomes in patients with supratentorial ICH. It may provide a promising target for developing new predictive tools targeting ICH.
Uptake of antepartum care services in a matrilineal-matrilocal society: a study of Garo indigenous women in Bangladesh
Authors: Chowdhury Suban Kumar
Published: January 2023

Background

The indigenous Garo is a close-knit matrilineal-matrilocal community. This community's expectant mothers receive less antepartum biomedical care, making them prone to maternal mortality. This study developed a conceptual framework to explore how the external environment, personal predispositions, enabling components and perceived antepartum care needs influence and generate a gap in antepartum biomedical care uptake.

Methods

The author used qualitative data from the study area. The data were collected through conducting 24 semi-structured interviews with purposively selected Garo women. After transcribing the data, the author generated the themes, grouped them into two broader domains, and analyzed them using the grounded theory approach.

Results

The emergent themes suggest adding the external environment (i.e., healthcare facilities' availability and services and culturally relevant healthcare services) to Anderson's behavioral model to understand indigenous women's antepartum care uptake disparity. Antepartum care uptake disparities arise when Andersen's behavioral model's other three drivers-personal predisposition, enabling components, and needs components-interact with the external environment. The interplay between enabling resources and the external environment is the conduit by which their predispositions and perceived needs are shaped and, thus, generate a disparity in antepartum care uptake. The data demonstrate that enabling resources include gendered power dynamics in families, home composition and income, men's spousal role, community practices of maternal health, and mother groups' and husbands' knowledge. Birth order, past treatment, late pregnancy, and healthcare knowledge are predispositions. According to data, social support, home-based care, mental health well-being, cultural norms and rituals, doctors' friendliness, affordable care, and transportation costs are perceived needs.

Conclusions

Garo family members (mothers/in-laws and male husbands) should be included in health intervention initiatives to address the problem with effective health education, highlighting the advantages of biomedical antepartum care. Health policymakers should ensure the availability of nearby and culturally appropriate pregnancy care services.
High resolution dermal ultrasound (US) combined with superficial radiation therapy (SRT) versus non-image guided SRT or external beam radiotherapy (XRT) in early-stage epithelial cancer: a comparison of studies
Authors: Yu Lio , Moloney Mairead , Zheng Songzhu , Rogers James
Published: January 2023

Background

To compare the effectiveness of high-resolution dermal ultrasound (US) guided superficial radiotherapy (SRT) to non-image-guided radiotherapy in the treatment of early-stage Non-Melanoma Skin Cancer (NMSC).

Methods

A high-resolution dermal ultrasound (US) image guided form of superficial radiation therapy (designated here as US-SRT) was developed in 2013 where the tumor configuration and depth can be visualized prior to, during, and subsequent to treatments, using a 22 megahertz (MHz) dermal ultrasound (US) with a doppler component. We previously published the results using this technology to treat 2917 early-stage epithelial cancers showing a high local control (LC) rate of 99.3%. We compared these results with similar American studies from a comprehensive literature search used in an article/guideline published by American Society of Radiation Oncology (ASTRO) on curative radiation treatment of basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and squamous cell carcinoma in-situ (SCCIS) lesions from 1988 to 2018. Only U.S. based studies with greater than 100 cases with similar patient/lesion characteristics and stages treated by external beam, electron, or superficial/orthovoltage radiation therapy were included in the criteria for selection. The resultant 4 studies had appropriate comparable cases identified and the data analyzed/calculated with regard to local control. Logistic regression analysis was performed comparing each study to US-SRT individually and collectively with stratification by histology (BCC, SCC, and SCCIS).

Results

US-SRT LC was found to be statistically superior to each of the 4 non-image-guided radiation therapy studies individually and collectively (as well as stratified by histology subtype) with p-values ranging from p < 0.0001 to p = 0.0438.

Conclusions

Results of US-SRT in local control were statistically significantly superior across the board versus non-image-guided radiation modalities in treatment of epithelial NMSC and should be considered a new gold standard for treatment of early-stage cutaneous BCC, SCC, and SCCIS.
Establishment and evaluation of nomogram for predicting intraventricular hemorrhage in neonatal acute respiratory distress syndrome
Authors: Arkin Nurbiya , Wang Yanmei , Wang Le
Published: January 2023

Background

Intraventricular hemorrhage (IVH) is the most common type of brain injury in newborns, especially in newborns with Neonatal acute respiratory distress syndrome (ARDS). IVH can cause brain parenchyma damage and long-term neurological sequelae in children. Early identification and prevention of sequelae are essential. This study aims to establish a predictive nomogram for the early prediction of IVH in newborns with ARDS.

Methods

From 2019 to 2021, we collected data from 222 infants diagnosed with ARDS in the Department of Neonatology, First Affiliated Hospital of Xinjiang Medical University. Infants have been randomly assigned to the training set (n = 161) or the validation set (n = 61) at a ratio of 7:3. Variables were screened using the Least Absolute Contract and Selection Operator (LASSO) regression to create a risk model for IVH in infants with ARDS. The variables chosen in the LASSO regression model were used to establish the prediction model using multivariate logistic regression analysis.

Results

We recognized 4 variables as independent risk factors for IVH in newborns with ARDS via LASSO analysis, consisting of premature rupture of membranes (PROM), pulmonary surfactant (PS) dosage, PH1 and Arterial partial pressure of oxygen (PaO21). The C-Index for this dataset is 0.868 (95% CI: 0.837–0.940) and the C index in bootstrap verification is 0.852 respectively. The analysis of the decision curve shows that the model can significantly improve clinical efficiency in predicting IVH. We also provide a website based on the model and open it to users for free, so that the model can be better applied to clinical practice.

Conclusion

In conclusion, the nomogram based on 4 factors shows good identification, calibration and clinical practicability. Our nomographs can help clinicians make clinical decisions, screen high-risk ARDS newborns, and facilitate early identification and management of IVH patients.
Transanal recto-anal anastomosis for treatment of rectal atresia: a review of 4 cases
Authors: Shehata Sameh , ElSawaf Mohamed , Kotb Mostafa
Published: January 2023

Introduction

Rectal atresia is a rare subtype of anorectal malformations in which the patients are born with a normal anal canal but have complete atresia located few centimeters proximal to the dentate line. We present the transanal end-to-end rectoanal anastomosis as a surgical technique for the management of these patients, highlight the outcomes, and emphasize on some clinical tips.

Methods

Four patients were diagnosed as having rectal atresia on clinical and radiological basis. All of them underwent single loop low sigmoid colostomy in the first 24 h. After 6 months, transanal end-to-end rectoanal anastomosis was performed followed by closure of the stoma 3 months later.

Results

The 2 cases that are older than 3 years demonstrated normal continence and are clean between bowel movements, while the other two showed good anal tone and passing stools between 1–3 times daily, being dry in between.

Conclusion

Transanal recto-anal anastomosis allows a safer route of anatomical reconstruction of the anorectum, therefore avoiding the potential complications associated with the other more invasive approaches.
Trends in the utilization of medicines sold in the private sector post- registration in South Africa and the implications for similar countries
Authors: Mpanza Ntobeko Magnate , Godman Brian , Keele Mothobi Godfrey , Matlala Moliehi
Published: January 2023

Background

Regulatory authorities register medicines for patients to access them within a reasonable period of time. There is a paucity of available data regarding the extent to which registered medicines reach the public after market authorisation is granted by the South African Health Products Regulatory Authority (SAHPRA). This is important since time spent by SAHPRA assessing medicines that are subsequently not launched onto the South African market means time wasted, which could be spent on assessing new medicines that address an unmet need in the country. Consequently, we initially analysed the time taken for registered medicines to reach patients and the relationship between medicines registered at SAHPRA and those subsequently dispensed in private pharmacies. The extent of registration of multiple sourced versus new patented medicines was also explored.

Methods

A retrospective, descriptive and quantitative investigation was conducted for medicines registered between 2014 and 2019. Registered and dispensed medicines were compared to establish accessibility post registration. Data sources included SAHPRA and IQVIA datasets. Microsoft Excel and SAS were used for data storage, analysis, and computation of descriptive statistical analysis.

Results

Of (N = 2175) registered medicines, only 358 (16.5%; 95% CI 15.0%—18.1%) were dispensed to patients, and out of 1735 medicines registered between 2015 and 2019, only 57 (3.3%; 95% CI 2.5%—4.2%) were dispensed during the study period. Medicines acting on the central nervous system were registered and dispensed the most at 21.0% and 18.0%, respectively, whereas antineoplastic and immunomodulation agents were registered and dispensed only 11% and 5%, respectively. A concern was that only 13.0% of registered medicines were originators, with most either as generics, including branded generics, or pseudo-generics.

Conclusion

Regulatory measures should be implemented to ensure increased medicine access post-registration for new originators, especially for priority disease areas that benefit patients. Mental health diseases and improved access to oncology medicines require special attention and further investigation in South Africa.
The effect of iliotibial band surgery at the hip: a systematic review
Authors: Storgaard Jensen Simon , Lund Kristina , Lange Jeppe
Published: January 2023

Background

Current literature presents a variety of surgical interventions aimed at modifying the iliotibial band (ITB) at the hip to relieve lateral hip pain (LHP). However, a focus towards the hip abductors as a main driver in LHP has evolved in the last decade, which could influence the indications for isolated ITB surgery. No previous review has been undertaken to evaluate isolated ITB surgery in LHP cases.

Purpose

The purpose of this systematic review was to evaluate isolated ITB surgery in LHP patients in relation to pain, snapping, use of non-surgical treatments postoperatively, and repeated surgery.

Methods

The study was reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The study was registered in Prospero (CRD42021216707) prior to initiation. A systematic search of literature on PubMed and Embase as well as bibliography screening on adult patients undergoing isolated ITB surgery with or without additional bursectomies was performed. Due to the lack of reliable data, no meta-analysis was performed.

Results

A total of 21 studies (360 patients) were considered eligible for inclusion. The snapping and non-snapping group consisted of 150 and 210 patients, respectively. The mean follow-up time in the snapping group was 30 months and 19 months in the non-snapping group. Utilizing different surgical techniques, complete pain relief was not achieved in 12% of patients in the snapping group and 36% of the patients in the non-snapping group. In the snapping group, snapping was eliminated in 95% of patients, and five of 150 patients (3%) had repeated surgery. Eight of nine non-snapping studies reported information regarding repeated surgery, in which seven of 205 patients (3%) received repeated surgery.

Conclusion

ITB surgery at the hip remains widely adopted, although only level 4 studies are available, and little information exists on the long-term clinical, as well as patient reported outcomes. Based on the available data, we found indication of a positive short-term outcome in LHP with snapping regarding elimination of snapping, pain reduction, reuse of non-surgical treatment, and repeated surgery. In LHP with no snapping, we found limited evidence supporting ITB surgery based on current literature.
Transvaginal natural orifice transluminal endoscopic surgery versus conventional vaginal surgery for sacrospinous ligament fixation of apical compartment prolapse: a retrospective analysis
Authors: Huang Lu , Yu Jie , Li Yan , Gong Zhao-Lin , Feng Dan , He Li , Lin Yong-Hong
Published: January 2023

Background

To objectively assess the safety, feasibility, advantages, and disadvantages of transvaginal natural orifice transluminal endoscopic surgery (vNOTES) versus conventional vaginal (CV) surgery for sacrospinous ligament fixation (SSLF).

Methods

We retrospectively analyzed the data of patients who underwent hysterectomy for SSLF via vNOTES or CV surgery due to apical compartment prolapse between April 2019 and April 2020 at our hospital. The patients were classified into the vNOTES group (n = 31) and CV surgery group (n = 51) based on surgical approach and their general characteristics and perioperative outcomes compared.

Results

The two groups had similar general characteristics. The anatomical success and bilateral salpingo-oophorectomy rates were higher in the vNOTES than CV surgery group, while the postoperative stay was shorter in the vNOTES than CV surgery group. All differences were statistically significant. However, there were no statistically significant intergroup differences in operation time, bilateral salpingectomy rate, colporrhaphy rate, postoperative visual analog scale score, estimated blood loss, hemoglobin decrease at 72 h postoperative, maximum body temperature at 72 h postoperative, complication rate, buttock pain, or Pelvic Floor Impact Questionnaire-7 and Pelvic Floor Distress Inventory Questionnaire-20 scores at 1 year postoperative.

Conclusions

VNOTES for SSLF was safe and feasible and resulted in superior objective and subjective outcomes versus CV surgery for SSLF. These findings suggest that vNOTES could be an alternative to CV surgery for SSLF.
Monitoring the clinical practice of palliative sedation (PALSED) in patients with advanced cancer: an international, multicentre, non-experimental prospective observational study protocol
Authors: Rijpstra Maaike , Vissers Kris , Centeno Carlos , Menten Johan , Radbruch Lukas , Mercadante Sebastiano , Van der Elst Michael , Adile Claudio , Arantzamendi Maria , Kuip Evelien , Payne Sheila , Preston Nancy , Hasselaar Jeroen
Published: January 2023

Background

Palliative sedation involves the intentional lowering of consciousness at the end of life. It can be initiated to relieve a patient’s burden caused by refractory symptoms at the end of life. The impact of palliative sedation needs to be clinically monitored to adjust the proper dose and regimen of sedative medication to ensure that patients are at ease and comfortable at the end of their lives. Although there is consensus among health care professionals and within guidelines that efficacy of palliative sedation needs to be closely monitored, there is no agreement about how, when, and by whom, this monitoring should be performed. The aim of this study is to evaluate the effects of palliative sedation by measuring the discomfort levels and sedation/agitation levels of the patients at regular timepoints. In addition, the clinical trajectories of those patients receiving palliative sedation will be monitored and recorded.

Methods

The study is an international prospective non-experimental observational multicentre study. Patients are recruited from in-patient palliative care settings in Belgium, Germany, Italy, Spain and the Netherlands. Adult patients with advanced cancer are monitored by using proxy observations of discomfort (DS-DAT) and depth of sedation/agitation levels (RASS-PAL) during palliative sedation. After the palliative sedation period, the care for the specific participant case is evaluated by one of the attending health care professionals and one relative via a questionnaire.

Discussion

This study will be the first international prospective multicenter study evaluating the clinical practice of palliative sedation including observations of discomfort levels and levels of sedation. It will provide valuable information about the practice of palliative sedation in European countries in terminally ill cancer patients. Results from this study will facilitate the formulation of recommendations for clinical practice on how to improve monitoring and comfort in patients receiving palliative sedation.

Trial registration

This study is registered at Clinicaltrials.gov since January 22, 2021, registration number: NCT04719702.
Total flavonoids of Chrysanthemum indicum L inhibit acute pancreatitis through suppressing apoptosis and inflammation
Authors: Yang Xiaojuan , Liu Yun , Zhong Chao , Hu Jia , Xu Song , Zhang Ping , He Ling
Published: January 2023

Acute pancreatitis (AP) is one of the most common acute abdomen. Inflammation and apoptosis are closely linked with AP development. Total flavonoids of Chrysanthemum indicum L (TFC) has been proved to inhibit inflammation and apoptosis. If TFC could suppress AP remains unclear. AP animal and cell models were established with Cerulein. The pancreatic tissue injury was measured with HE staining. Inflammatory factors were detected with ELISA method. The protein expression was evaluated with Western blotting. Inhibition of AP in vivo was achieved by TFC by inhibiting serum amylase, myeloperoxidase (MPO), and water content of pancreatic tissue. The increased inflammatory response and activation of NF-κB signaling pathway in AP rats were inhibited after TFC treatment. The activation of NF-κB signaling pathway, increase of cell apoptosis and inflammatory factors in AR42J cells were suppressed by TFC. We demonstrated that TFC could significantly inhibit AP through restraining serum amylase, MPO, water content of pancreatic tissue, inflammation levels, apoptosis, and NF-κB signaling pathway activation. This study might clarify the potential inhibition mechanism of TFC in AP development.
Synergistic inhibitory activity of Glycyrrhizae Radix and Rubi Fructus extracts on biofilm formation of Streptococcus mutans
Authors: Ham Youngseok , Kim Tae-Jong
Published: January 2023

Background

Streptococcus mutans is a bacterium that causes oral diseases. Plaque, a biofilm produced by S. mutans and other bacteria, makes it difficult to remove cariogenic oral microorganisms, including biofilm producers. Glucan synthesis by glucosyltransferase is one of the mechanisms underlying plaque formation. This study demonstrates the effectiveness of inhibiting biofilm formation by interfering with the glucosyltransferase activity of S. mutans using edible herbal medicines.

Methods

This study investigated the inhibitory activity of Glycyrrhizae Radix extract, Rubi Fructus extract, glycyrrhizin from Glycyrrhizae Radix, and ellagic acid from Rubi Fructus against glucosyltransferase activity of S. mutans. Enzyme kinetic analysis identified the mechanism by which glycyrrhizin and ellagic acid inhibit enzyme activity.

Results

The conditions for synergistically inhibiting biofilm formation by combining Glycyrrhizae Radix and Rubi Fructus extracts were identified. Biofilm formation was also synergistically inhibited by mixing their respective active constituents, glycyrrhizin and ellagic acid. Glycyrrhizin and ellagic acid inhibited glucosyltransferase via noncompetitive and uncompetitive mechanisms, respectively, indicating that they inhibit it via distinct mechanisms.

Conclusions

This study presents an effective oral hygiene method using the synergistic activity of two natural plant extracts to inhibit biofilm formation through different inhibitory mechanisms against glucosyltransferase of S. mutans.
Primary health care nurses’ mental health knowledge and attitudes towards patients and mental health care in a South African metropolitan municipality
Authors: Kigozi-Male Nanteza Gladys , Heunis James Christoffel , Engelbrecht Michelle Catherine
Published: January 2023

Background

In South Africa, there are on-going calls to integrate mental health services into existing primary health care (PHC) programmes such as Tuberculosis (TB). Successful service integration and quality service delivery partially depend on healthcare providers’ mental health-related knowledge and attitudes. The aim of this study was to assess PHC nurses’ mental health knowledge and attitudes towards mental health patients and mental health care.

Methods

This was a cross-sectional survey involving the distribution of self-administered questionnaires among PHC nurses across 47 clinics. Data on socio-demographics, stigma-related mental health knowledge, and nurses’ attitudes towards people with mental health problems and mental health care were subjected to descriptive and multiple regression analyses.

Results

Out of 205 respondents, the majority were female (n = 178, 86.8%). The nurses’ median age was 50 (interquartile range: 39–56). Their mean mental health knowledge score was 23.0 (standard deviation [sd]: 3.07) out of 30. Nurses were less knowledgeable about the employment (n = 95, 46.3%), recovery (n = 112, 54.6%), and help-seeking behaviour (n = 119, 58.0%) of people with mental health problems. Professional nurses had a significantly higher mean mental health knowledge score than enrolled/assistant nurses (22.8 vs. 21.1, t203 = 4.775, p < 0.001). Regarding attitudes, the nurses’ mean attitude score was 40.68 (sd: 9.70) out of 96. Two in every five nurses (n = 91, 44.4%) scored above the mean attitude score, implying that they were inclined to have negative (stigmatising) attitudes towards people with mental problems and mental health care. Age (p = 0.048), job category (p < 0.001), and prior in-service mental health training (p = 0.029) made a unique contribution to predicting nurses’ attitudes.

Conclusion

Gaps were established in PHC nurses’ stigma-related mental health knowledge. A significant proportion of nurses had a propensity for negative (stigmatising) attitudes towards mental health patients and mental health care. Efforts towards integration of mental health into TB services in this metropolitan and similar settings should address mental health knowledge deficits and factors influencing nurses’ negative attitudes. In-service training on mental health should be optimised, with attention to older nurses and enrolled/nursing assistants.
Exploring genes for immunoglobulin A nephropathy: a summary data-based mendelian randomization and FUMA analysis
Authors: Zhang Qian , Zhang Kang , Zhu Yining , Yuan Guangwei , Yang Jingyun , Zhang Minmin
Published: January 2023

Background

Immunoglobulin A nephropathy (IgAN) is a complex autoimmune disease, and the exact pathogenesis remains to be elucidated. This study aimed to explore genes underlying the pathogenesis of IgAN.

Methods

We conducted the summary data-based Mendelian randomization (SMR) analysis and performed functional mapping and annotation using FUMA to explore genetic loci that are potentially involved in the pathogenies of IgAN. Both analyses used summarized data of a recent genome-wide association study (GWAS) on IgANs, which included 477,784 Europeans (15,587 cases and 462,197 controls) and 175,359 East Asians (71 cases and 175,288 controls). We performed SMR analysis using Consortium for the Architecture of Gene Expression (CAGE) expression quantitative trait loci (eQTL) data and replicated the analysis using Genotype-Tissue Expression (GTEx) eQTL data.

Results

Using the CAGE eQTL data, our SMR analysis identified 32 probes tagging 25 unique genes whose expression were pleiotropically associated with IgAN, with the top three probes being ILMN_2150787 (tagging HLA-C, PSMR= 2.10 × 10–18), ILMN_1682717 (tagging IER3, PSMR= 1.07 × 10–16) and ILMN_1661439 (tagging FLOT1, PSMR=1.16 × 10–14). Using GTEx eQTL data, our SMR analysis identified 24 probes tagging 24 unique genes whose expressions were pleiotropically associated with IgAN, with the top three probes being ENSG00000271581.1 (tagging XXbac-BPG248L24.12, PSMR= 1.44 × 10–10), ENSG00000186470.9 (tagging BTN3A2, PSMR= 2.28 × 10–10), and ENSG00000224389.4 (tagging C4B, PSMR= 1.23 × 10 –9). FUMA analysis identified 3 independent, significant and lead SNPs, 2 genomic risk loci and 39 genes that are potentially involved in the pathogenesis of IgAN.

Conclusion

We identified many genetic variants/loci that are potentially involved in the pathogenesis of IgAN. More studies are needed to elucidate the exact mechanisms of the identified genetic variants/loci in the etiology of IgAN.
The predictive value of nontraditional lipid parameters for intracranial and extracranial atherosclerotic stenosis: a hospital-based observational study in China
Authors: Yu Shun , Yan Lihong , Yan Junwei , Sun Xiaozhi , Fan Meixia , Liu Huanhuan , Li Yongxin , Guo Mingjin
Published: January 2023

Background

Ischemic strokes are primarily caused by intracranial and extracranial atherosclerotic stenosis. Nontraditional lipid parameters broaden traditional lipid profiles, better reflect the metabolism and interaction between different lipid components, and optimize the predictive ability of lipid profiles for atherosclerotic diseases. This research was carried out to investigate the predictive value of nontraditional lipid parameters for intracranial or extracranial atherosclerotic stenosis.

Methods

The investigation collected data from inpatients who underwent cervical vascular ultrasonography, carotid CTA, cerebral artery CTA or MRA, and brain MRI or CT from December 2014 to December 2021. The nontraditional lipid parameters were calculated by collecting traditional lipid parameters. To evaluate the predictive power of nontraditional lipid parameters, logistic regression and receiver operating characteristic curve (ROC) analyses were performed.

Results

Based on the inclusion and exclusion criteria, 545 patients were included. According to the imaging results, inpatients were divided into two groups, including no intracranial or extracranial atherosclerotic stenosis (n = 250) and intracranial or extracranial atherosclerotic stenosis (AS, n = 295). Among them, AS was further divided into three subgroups: intracranial atherosclerotic stenosis (ICAS), extracranial atherosclerotic stenosis (ECAS) and combined intracranial and extracranial atherosclerotic stenosis (IECAS). Logistic regression analysis showed that nontraditional lipid parameters, including the atherogenic index of plasma (AIP), remnant cholesterol (RC), nonhigh-density lipoprotein cholesterol (non-HDL-C), lipoprotein combine index (LCI), atherogenic coefficient (AC), Castelli’s index-I (CRI-I) and Castelli’s index-II (CRI-II), were significantly correlated with intracranial or extracranial atherosclerotic stenosis (P < 0.05). Compared with other nontraditional lipid parameters, regardless of adjusting for potential confounding factors, AIP had a greater OR value in ICAS (OR = 4.226, 95% CI: 1.681–10.625), ECAS (OR = 2.993, 95% CI: 1.119–8.003) and IECAS (OR = 4.502, 95% CI: 1.613–12.561). ROC curve analysis revealed that nontraditional lipid parameters had good predictive power for intracranial or extracranial atherosclerotic stenosis.

Conclusions

This Chinese hospital-based study demonstrates that nontraditional lipid parameters (AIP, LCI, RC, CRI-II, AC, CRI-I and non-HDL-C) are effective predictors of intracranial and extracranial atherosclerotic stenosis, of which AIP may be a significant risk factor for predicting atherosclerotic arterial stenosis in the intracranial or extracranial regions.