bluuebunny/crossref_metadata_2025 huggingface dataset:
One-stage tubeless percutaneous nephrolithotomy for asymptomatic calculous pyonephrosis
Authors: Guo Shijie , Zhang Xicai , Li Fengyue , Sun Chunyue , Zhang Yonghe , Cao Xiande
Published: March 2022

Background

In recent years, the safety and effectiveness of one-stage percutaneous nephrolithotomy (PCNL) for the treatment of calculous pyonephrosis have been proven. In order to further reduce postoperative pain and hospital stay, we first proposed and practiced the idea of one-stage tubeless percutaneous nephrolithotomy for calculous pyonephrosis.

Methods

A retrospective analysis was performed of case data of 30 patients with asymptomatic calculous pyonephrosis treated in our center with one-stage PCNL from January 2016 to January 2021. Patients were routinely given 20 mg of furosemide and 10 mg of dexamethasone sodium phosphate injection intravenously at the beginning of anesthesia. Among them, 27 patients successfully underwent one-stage tubeless percutaneous nephrolithotomy, while 3 cases were given indwelling nephrostomy tubes because of proposed second-stage surgery or the number of channels was greater than or equal to 3. All patients were operated on by the same surgeon.

Results

Preoperatively, 11 of 30 patients (8 men and 22 women) had positive urine bacterial cultures, and all were given appropriate antibiotics based on drug sensitivity tests. All patients completed the surgery successfully. The mean operative time was 66.6 ± 34.7 min, the mean estimated blood loss was 16.67 ± 14.34 mL and the mean postoperative hospital stay was 5.0 ± 3.1 days. The mean postoperative hospital stay was 4.6 ± 2.5 days among the 27 patients with one-stage tubeless percutaneous nephrolithotomy. Of the 3 patients with postoperative fever, 2 had the tubeless technique applied. One patient with 3 channels was given renal artery interventional embolization for control of postoperative bleeding. None of the 30 patients included in the study developed sepsis. The final stone-free rate was 93.3% (28/30) on repeat computed tomography at 1 month postoperatively. The final stone-free rate was 92.6% in the 27 patients undergoing one-stage tubeless percutaneous nephrolithotomy (25/27).

Conclusions

One-stage tubeless PCNL is an available and safe option in carefully evaluated and selected calculous pyonephrosis patients.
Development of a CHO cell line for stable production of recombinant antibodies against human MMP9
Authors: Ryu Jina , Kim Eun-Jung , Kim Joo-Kyung , Park Tai Hyun , Kim Byung-Gee , Jeong Hee-Jin
Published: March 2022

Background

Human matrix metalloproteinase 9 (hMMP9) is a biomarker in several diseases, including cancer, and the need for developing detectors and inhibitors of hMMP9 is increasing. As an antibody against hMMP9 can be selectively bound to hMMP9, the use of anti-MMP9 antibody presents new possibilities to address hMMP9-related diseases. In this study, we aimed to establish a stable Chinese hamster ovary (CHO) cell line for the stable production of antibodies against hMMP9.

Results

Weconstructed recombinant anti-hMMP9 antibody fragment-expressing genes and transfected these to CHO cells. We chose a single clone, and successfully produced a full-sized antibody against hMMP9 with high purity, sensitivity, and reproducibility. Subsequently, we confirmed the antigen-binding efficiency of the antibody.

Conclusions

We developed a novel recombinant anti-hMMP9 antibody via a CHO cell-based mammalian expression system, which has a high potential to be used in a broad range of medical and industrial areas.
Economic models of community-based falls prevention: a systematic review with subsequent commissioning and methodological recommendations
Authors: Kwon Joseph , Squires Hazel , Franklin Matthew , Lee Yujin , Young Tracey
Published: March 2022

Background

Falls impose significant health and economic burdens among older populations, making their prevention a priority. Health economic models can inform whether the falls prevention intervention represents a cost-effective use of resources and/or meet additional objectives such as reducing social inequities of health. This study aims to conduct a systematic review (SR) of community-based falls prevention economic models to: (i) systematically identify such models; (ii) synthesise and critically appraise modelling methods/results; and (iii) formulate methodological and commissioning recommendations.

Methods

The SR followed PRISMA 2021 guideline, covering the period 2003–2020, 12 academic databases and grey literature. A study was included if it: targeted community-dwelling persons aged 60 and over and/or aged 50–59 at high falls risk; evaluated intervention(s) designed to reduce falls or fall-related injuries; against any comparator(s); reported outcomes of economic evaluation; used decision modelling; and had English full text. Extracted data fields were grouped by: (A) model and evaluation overview; (B) falls epidemiology features; (C) falls prevention intervention features; and (D) evaluation methods and outcomes. A checklist for falls prevention economic evaluations was used to assess reporting/methodological quality. Extracted fields were narratively synthesised and critically appraised to inform methodological and commissioning recommendations. The SR protocol is registered in the Prospective Register of Systematic Reviews (CRD42021232147).

Results

Forty-six models were identified. The most prevalent issue according to the checklist was non-incorporation of all-cause care costs. Based on general population, lifetime models conducting cost-utility analyses, seven interventions produced favourable ICERs relative to no intervention under the cost-effectiveness threshold of US$41,900 (£30,000) per QALY gained; of these, results for (1) combined multifactorial and environmental intervention, (2) physical activity promotion for women, and (3) targeted vitamin D supplementation were from validated models. Decision-makers should explore the transferability and reaches of interventions in their local settings. There was some evidence that exercise and home modification exacerbate existing social inequities of health. Sixteen methodological recommendations were formulated.

Conclusion

There is significant methodological heterogeneity across falls prevention models. This SR’s appraisals of modelling methods should facilitate the conceptualisation of future falls prevention models. Its synthesis of evaluation outcomes, though limited to published evidence, could inform commissioning.
Mental healthcare-seeking behavior during the perinatal period among women in rural Bangladesh
Authors: Dutta Goutam Kumar , Sarker Bidhan Krishna , Ahmed Helal Uddin , Bhattacharyya Dipika Shankar , Rahman Md. Musfikur , Majumder Ratna , Biswas Taposh Kumar
Published: March 2022

Introduction

Mental health conditions are of rising concern due to their increased contribution to the global burden of disease. Mental health issues are inextricably linked with other socio-cultural and health dimensions, especially in the rural areas in developing countries. The complex relationship between mental health issues and socio-cultural settings may largely toll upon healthcare-seeking behavior. So, it urges to document the current status of mental healthcare-seeking behavior during the perinatal period among rural women in Bangladesh to develop a context-specific intervention in the future.

Methods

This study was carried out in one sub-district in Bangladesh from April 2017 to June 2018. We conducted 21 In-depth Interviews (IDIs) and seven Focus Group Discussions (FGDs) with different groups of purposively selected participants. After collecting the recorded interview and making the verbatim transcription, the data were coded throughAtlasti5.7.a. Data were analyzed thematically to interpret the findings.

Results

Two-thirds of the total respondents did not seek mental healthcare during the perinatal period at the community level. They also did not know about the mental health service provider or the facility to get set these services. Only one respondent out of twenty-one sought maternal mental healthcare from a gynecologist from a private hospital. Socio-cultural factors such as social stigma, traditional beliefs and practices, social and religious taboos, and social capital negatively influence healthcare-seeking behaviors. Besides, the community-level service providers were not found to be adequately trained and did not have proper guidelines regarding its management.

Conclusion

The findings provide evidence that there is an urgent need to increase the awareness for service users and formulate a guideline for the community-level service provider to manage maternal mental problems during the perinatal period of women in rural Bangladesh.
Sociodemographic characteristics of patients and their use of post-bariatric contouring surgery in the US
Authors: Al-Sumaih Ibrahim , Donnelly Michael , O’Neill Ciaran
Published: March 2022

Background

Expansion of healthcare insurance coverage to bariatric surgeries has led to an increased demand from patients for post-bariatric contouring surgeries. This study examined the relationship between the use of contouring procedures on post-bariatric surgery patients, clinical need and sociodemographic factors.

Methods

Data were extracted from the Healthcare Cost and Utilization Project (HCUP) Nationwide Ambulatory Surgery Sample (NASS) regarding hospital-owned ambulatory surgical centres in the US. Episodes without missing values relating to patients, 18 years old or above were the primary unit of analysis. Episodes were excluded if the field regarding expected payer was reported as “no charge.” The primary outcome was the likelihood of panniculectomy, abdominoplasty, and mastopexy among post-bariatric surgery patients; and the degree to which uptake of these types of contouring surgery were associated with age, gender, median households’ income, expected payer, patient’s location, and comorbidity.

Results

A total of 66,368 weighted episodes of care received by patients who had had bariatric surgery were extracted (54,684 female [82.4%]; mean age, 51.3 [SD, 12.1]; 6219 episodes had contouring surgeries [9.37%]). Panniculectomy was the most common post-bariatric contouring procedure (3.68%). Uptake of post-bariatric contouring procedures was associated with age, sex, payment type, area-based measures of median household income, and patient location. Compared to Medicare insured patients, the odds of receiving contouring surgery among self-payers were 1.82 (95% CI, 1.47 to 2.26) for panniculectomy, 14.79 (95% CI, 12.19 to 17.93) for abdominoplasty and 47.97 (95% CI, 32.76 to 70.24) for mastopexy. Rank order of comorbidity profiles also differed between insured and self-paying recipients of contouring surgery.

Conclusions

Insurance status of bariatric surgery patients and their sex were strongly associated with receipt of a range of contouring procedures. Self-payments were associated with a doubling of the odds of having panniculectomy and an increase in the odds to approximately 14 times for abdominoplasty and 48 times for mastopexy. Thus, access to contouring surgery by post-bariatric patients may be disproportionately dependent on personal preference supported by ability to pay rather than clinical need. Further research is needed to examine the impact of contouring or delayed/denied contouring on health status.
Network characteristics of a referral system for patients with hypertension in Western Kenya: results from the Strengthening Referral Networks for Management of Hypertension Across the Health System (STRENGTHS) study
Authors: Thakkar Aarti , Valente Thomas , Andesia Josephine , Njuguna Benson , Miheso Juliet , Mercer Tim , Mugo Richard , Mwangi Ann , Mwangi Eunice , Pastakia Sonak D. , Pathak Shravani , Pillsbury Mc Kinsey M. , Kamano Jemima , Naanyu Violet , Williams Makeda , Vedanthan Rajesh , Akwanalo Constantine , Bloomfield Gerald S.
Published: March 2022

Background

Health system approaches to improve hypertension control require an effective referral network. A national referral strategy exists in Kenya; however, a number of barriers to referral completion persist. This paper is a baseline assessment of a hypertension referral network for a cluster-randomized trial to improve hypertension control and reduce cardiovascular disease risk.

Methods

We used sociometric network analysis to understand the relationships between providers within a network of nine geographic clusters in western Kenya, including primary, secondary, and tertiary care facilities. We conducted a survey which asked providers to nominate individuals and facilities to which they refer patients with controlled and uncontrolled hypertension. Degree centrality measures were used to identify providers in prominent positions, while mixed-effect regression models were used to determine provider characteristics related to the likelihood of receiving referrals. We calculated core-periphery correlation scores (CP) for each cluster (ideal CP score = 1.0).

Results

We surveyed 152 providers (physicians, nurses, medical officers, and clinical officers), range 10–36 per cluster. Median number of hypertensive patients seen per month was 40 (range 1–600). While 97% of providers reported referring patients up to a more specialized health facility, only 55% reported referring down to lower level facilities. Individuals were more likely to receive a referral if they had higher level of training, worked at a higher level facility, were male, or had more job experience. CP scores for provider networks range from 0.335 to 0.693, while the CP scores for the facility networks range from 0.707 to 0.949.

Conclusions

This analysis highlights several points of weakness in this referral network including cluster variability, poor provider linkages, and the lack of down referrals. Facility networks were stronger than provider networks. These shortcomings represent opportunities to focus interventions to improve referral networks for hypertension.

Trial registration

Trial Registered on ClinicalTrials.gov NCT03543787, June 1, 2018.
The relationship between capacity and utilization of nonpharmacologic therapies in the US Military Health System
Authors: Bolton Rendelle , Ritter Grant , Highland Krista , Larson Mary Jo
Published: March 2022

Background

Nonpharmacologic therapies (NPTs) are recommended as first-line treatments for pain, however the impact of expanding professional capacity to deliver these therapies on use has not been extensively studied. We sought to examine whether an effort by the US Military Health System (MHS) to improve access to NPTs by expanding professional capacity increased NPT utilization in a cohort at higher risk for pain – Army soldiers returning from deployment.

Methods

Our study involved secondary analysis of MHS workforce data derived from the Defense Medical Human Resources System Internet (DMHRSi), and healthcare utilization data obtained from two ambulatory record systems of the Military Health System (MHS) for a sample of 863,855 Army soldiers previously deployed to Iraq or Afghanistan over a 10-year period (2008–2017). We measured clinical provider capacity in three occupational groups responsible for pain management at 130 military treatment facilities (MTFs): physical therapy, chiropractic, and behavioral health, measured annually as full-time equivalence per 100,000 patients served at each MTF. Utilization in both direct and purchased care settings was measured as annual mean NPT users per 1000 sample members and mean encounters per NPT user. Generalized estimating equation models estimated the associations of facility-level occupational capacity measures and facility-level utilization NPT measures.

Results

In 2008, nearly all MTFs had some physical therapist and behavioral health provider capacity, but less than half had any chiropractor capacity. The largest increase in capacity from 2008 to 2017 was for chiropractors (89%) followed by behavioral health providers (77%) and physical therapists (37%). Models indicated that increased capacity of physical therapists and chiropractors were associated with significantly increased utilization of six out of seven NPTs. Acupuncture initiation was associated with capacity increases in each occupation. Increased professional capacity in MTFs was associated with limited but positive effects on NPT utilization in purchased care.

Conclusions

Increasing occupational capacity in three professions responsible for delivering NPTs at MTFs were associated with growing utilization of seven NPTs in this Army sample. Despite increasing capacity in MTFs, some positive associations between MTF capacity and purchased care utilization suggest an unmet need for NPTs. Future research should examine if these changes lead to greater receipt of guideline-concordant pain management.
Clinical presentation, diagnostic findings and outcome of dogs undergoing surgical resection for intracranial meningioma: 101 dogs
Authors: Forward Alexander K. , Volk Holger Andreas , Cherubini Giunio Bruto , Harcourt-Brown Tom , Plessas Ioannis N. , Garosi Laurent , De Decker Steven
Published: March 2022

Background

Meningioma is the most common primary brain neoplasm in dogs. Further information is required regarding the expected long-term prognosis of dogs following the surgical resection of an intracranial meningioma together with the influence of adjunctive therapies. Whilst there have been several studies reporting the long-term outcome of intracranial meningioma resection following surgery alone, surgery with the use of an ultrasonic aspirator, surgery combined with radiotherapy and surgery combined with the addition of hydroxyurea, it is currently unclear which type of adjunctive therapy is associated with the most favourable outcomes. The objective of this study is to describe the presentation and outcome of dogs undergoing surgery for the resection of an intracranial meningioma and the effect of clinical factors, adjunctive therapies and meningioma histopathological subtype on the long-term outcome.

Results

A hundred and one dogs that had intracranial surgery for meningioma resection were investigated from four referral centres. 94% of dogs survived to hospital discharge with a median survival time of 386 days. Approximately 50% of dogs survived for less than a year, 25% survived between 1 and 2 years, 15% survived between 2 and 3 years and 10% survived for greater than 3 years following discharge from hospital. One or more adjunctive therapies were used in 75 dogs and the analysis of the data did not reveal a clear benefit of a specific type of adjunctive therapy. Those dogs that had a transfrontal approach had a significantly reduced survival time (MST 184 days) compared to those dogs that had a rostrotentorial approach (MST 646 days;p < 0.05). There was no association between meningioma subtype and survival time.

Conclusions

This study did not identify a clear benefit of a specific type of adjunctive therapy on the survival time. Dogs that had a transfrontal approach had a significantly reduced survival time. Intracranial surgery for meningioma resection offers an excellent prognosis for survival to discharge from hospital with a median long term survival time of 386 days.
The role of the M-band myomesin proteins in muscle integrity and cardiac disease
Authors: Lamber Ekaterina P. , Guicheney Pascale , Pinotsis Nikos
Published: March 2022

Transversal structural elements in cross-striated muscles, such as the M-band or the Z-disc, anchor and mechanically stabilize the contractile apparatus and its minimal unit—the sarcomere. The ability of proteins to target and interact with these structural sarcomeric elements is an inevitable necessity for the correct assembly and functionality of the myofibrillar apparatus. Specifically, the M-band is a well-recognized mechanical and signaling hub dealing with active forces during contraction, while impairment of its function leads to disease and death. Research on the M-band architecture is focusing on the assembly and interactions of the three major filamentous proteins in the region, mainly the three myomesin proteins including their embryonic heart (EH) isoform, titin and obscurin. These proteins form the basic filamentous network of the M-band, interacting with each other as also with additional proteins in the region that are involved in signaling, energetic or mechanosensitive processes. While myomesin-1, titin and obscurin are found in every muscle, the expression levels of myomesin-2 (also known as M-protein) and myomesin-3 are tissue specific: myomesin-2 is mainly expressed in the cardiac and fast skeletal muscles, while myomesin-3 is mainly expressed in intermediate muscles and specific regions of the cardiac muscle. Furthermore, EH-myomesin apart from its role during embryonic stages, is present in adults with specific cardiac diseases. The current work in structural, molecular, and cellular biology as well as in animal models, provides important details about the assembly of myomesin-1, obscurin and titin, the information however about the myomesin-2 and -3, such as their interactions, localization and structural details remain very limited. Remarkably, an increasing number of reports is linking all three myomesin proteins and particularly myomesin-2 to serious cardiovascular diseases suggesting that this protein family could be more important than originally thought. In this review we will focus on the myomesin protein family, the myomesin interactions and structural differences between isoforms and we will provide the most recent evidence why the structurally and biophysically unexplored myomesin-2 and myomesin-3 are emerging as hot targets for understanding muscle function and disease.
Long non-coding RNA LINC00680 functions as a ceRNA to promote esophageal squamous cell carcinoma progression through the miR-423-5p/PAK6 axis
Authors: Xue Song-tao , Zheng Bin , Cao Shi-qiang , Ding Jian-cheng , Hu Guo-sheng , Liu Wen , Chen Chun
Published: March 2022

Background

Esophageal squamous cell carcinoma (ESCC) is a common invasive malignancy worldwide with poor clinical outcomes. Increasing amount of long non-coding RNAs (lncRNAs) have been reported to be involved in cancer development. However, lncRNAs that are functional in ESCC and the underlying molecular mechanisms remain largely unknown.

Methods

Transcriptomic analysis was performed to identify dysregulated lncRNAs in ESCC tissue samples. The high expression of LINC00680 in ESCC was validated by RT-qPCR, and the oncogenic functions of LINC00680 was investigated by cell proliferation, colony formation, migration and invasion assays in ESCC cells in vitro and xenografts derived from ESCC cells in mice. RNA-seq, competitive endogenous RNA (ceRNA) network analysis, and luciferase reporter assays were carried out to identify LINC00680 target genes and the microRNAs (miRNAs) bound to LINC00680. Antisense oligonucleotides (ASOs) were used for in vivo treatment.

Results

Transcriptome profiling revealed that a large number of lncRNAs was dysregulated in ESCC tissues. Notably, LINC00680 was highly expressed, and upregulation of LINC00680 was associated with large tumor size, advanced tumor stage, and poor prognosis. Functionally, knockdown of LINC00680 restrained ESCC cell proliferation, colony formation, migration, and invasion in vitro and inhibited tumor growth in vivo. Mechanistically, LINC00680 was found to act as a ceRNA by sponging miR-423-5p to regulate PAK6 (p21-activated kinase 6) expression in ESCC cells. The cell viability and motility inhibition induced by LINC00680 knockdown was significantly reversed upon PAK6 restoration and miR-423-5p inhibition. Furthermore, ASO targeting LINC00680 substantially suppressed ESCC both in vitro and in vivo.

Conclusions

An oncogenic lncRNA, LINC00680, was identified in ESCC, which functions as a ceRNA by sponging miR-423-5p to promote PAK6 expression and ESCC. LINC00680/miR-423-5p/PAK6 axis may serve as promising diagnostic and prognostic biomarkers and therapeutic targets for ESCC.
Lenvatinib inhibits the growth of gastric cancer patient-derived xenografts generated from a heterogeneous population
Authors: Karalis John D. , Yoon Lynn Y. , Hammer Suntrea T. G. , Hong Changjin , Zhu Min , Nassour Ibrahim , Ju Michelle R. , Xiao Shu , Castro-Dubon Esther C. , Agrawal Deepak , Suarez Jorge , Reznik Scott I. , Mansour John C. , Polanco Patricio M. , Yopp Adam C. , Zeh Herbert J. , Hwang Tae Hyun , Zhu Hao , Porembka Matthew R. , Wang Sam C.
Published: March 2022

Background

Lenvatinib is a multitargeted tyrosine kinase inhibitor that is being tested in combination with immune checkpoint inhibitors to treat advanced gastric cancer; however, little data exists regarding the efficacy of lenvatinib monotherapy. Patient-derived xenografts (PDX) are established by engrafting human tumors into immunodeficient mice. The generation of PDXs may be hampered by growth of lymphomas. In this study, we compared the use of mice with different degrees of immunodeficiency to establish PDXs from a diverse cohort of Western gastric cancer patients. We then tested the efficacy of lenvatinib in this system.

Methods

PDXs were established by implanting gastric cancer tissue into NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) or Foxn1nu (nude) mice. Tumors from multiple passages from each PDX line were compared histologically and transcriptomically. PDX-bearing mice were randomized to receive the drug delivery vehicle or lenvatinib. After 21 days, the percent tumor volume change (%Δvtumor) was calculated.

Results

23 PDX models were established from Black, non-Hispanic White, Hispanic, and Asian gastric cancer patients. The engraftment rate was 17% (23/139). Tumors implanted into NSG (16%; 18/115) and nude (21%; 5/24) mice had a similar engraftment rate. The rate of lymphoma formation in nude mice (0%; 0/24) was lower than in NSG mice (20%; 23/115; p < 0.05). PDXs derived using both strains maintained histologic and gene expression profiles across passages. Lenvatinib treatment (mean %Δvtumor: -33%) significantly reduced tumor growth as compared to vehicle treatment (mean %Δvtumor: 190%; p < 0.0001).

Conclusions

Nude mice are a superior platform than NSG mice for generating PDXs from gastric cancer patients. Lenvatinib showed promising antitumor activity in PDXs established from a diverse Western patient population and warrants further investigation in gastric cancer.
Non-linear relationship between the body roundness index and incident type 2 diabetes in Japan: a secondary retrospective analysis
Authors: Wu Liling , Pu Hailu , Zhang Man , Hu Haofei , Wan Qijun
Published: March 2022

Background

Body roundness index (BRI) is one of the obesity-related anthropometric indices. However, studies on the relationship between BRI and diabetes risk is limited. The purpose of this study was to explore the relationship between baseline BRI and incident type 2 diabetes mellitus (T2DM) in the Japanese population.

Methods

A retrospective longitudinal study of 15,310 participants in a physical examination program at Murakami Memorial Hospital in Japan from 2004 to 2015. The association between BRI levels and incident T2DM was analyzed by Cox proportional-hazards regression, smooth curve fitting, subgroup analyses, and a set of sensitivity analyses. Receiver operating characteristic curve analysis was used to assess the ability of BRI to predict diabetes.

Result

Baseline BRI levels were elevated in participants who developed T2DM. Baseline BRI levels were positively associated with incident T2DM after adjusting confounding variables (HR = 1.570, 95% CI 1.360–1.811). Additionally, we did a set of sensitivity analyses to ensure the robustness of the results. There was also a non-linear relationship between BRI and incident diabetes in both genders, and the inflection point of BRI was 4.137 in females and 3.146 in males. We found a strong positive correlation between BRI and the incidence of diabetes on the right of the inflection point (Male: HR = 1.827, 95% CI 1.449–2.303; Female: HR = 4.189, 95% CI 1.862–9.421). What’s more, among the anthropometric indices, BRI showed the optimal capability to predict T2DM (Male: AUC = 0.706, 95% CI 0.674–0.738; Female: AUC = 0.735, 95% CI 0.676–0.795).

Conclusion

An elevated BRI level in baseline was independently associated with incident T2DM. Baseline BRI improves the identification of patients at risk of T2DM and may enable early and optimized therapy to improve their outcomes.
Deconvolution of the epigenetic age discloses distinct inter-personal variability in epigenetic aging patterns
Authors: Shahal Tamar , Segev Elad , Konstantinovsky Thomas , Marcus Yonit , Shefer Gabi , Pasmanik-Chor Metsada , Buch Assaf , Ebenstein Yuval , Zimmet Paul , Stern Naftali
Published: March 2022

Background

The epigenetic age can now be extrapolated from one of several epigenetic clocks, which are based on age-related changes in DNA methylation levels at specific multiple CpG sites. Accelerated aging, calculated from the discrepancy between the chronological age and the epigenetic age, has shown to predict morbidity and mortality rate. We assumed that deconvolution of epigenetic age to its components could shed light on the diversity of epigenetic, and by inference, on inter-individual variability in the causes of biological aging.

Results

Using the Horvath original epigenetic clock, we identified several CpG sites linked to distinct genes that quantitatively explain much of the inter-personal variability in epigenetic aging, with CpG sites related to secretagogin and malin being the most variable. We show that equal epigenetic age in different subjects can result from variable contribution size of the same CpG sites to the total epigenetic age. In a healthy cohort, the most variable CpG sites are responsible for accelerated and decelerated epigenetic aging, relative to chronological age.

Conclusions

Of the 353 CpG sites that form the basis for the Horvath epigenetic age, we have found the CpG sites that are responsible for accelerated and decelerated epigenetic aging in healthy subjects. However, the relative contribution of each site to aging varies between individuals, leading to variable personal aging patterns. Our findings pave the way to form personalized aging cards allowing the identification of specific genes related to CpG sites, as aging markers, and perhaps treatment of these targets in order to hinder undesirable age drifting.
Examining the interaction of different factors on pointing precision when using handheld laser pointers
Authors: Tse Choi Yeung Andy , Kong Pui Wah , Poh Jun Jie , Fong Daniel T. P.
Published: March 2022

Objective

Laser pointers are common teaching tools used during lessons. The pointing precision may influence the teaching effectiveness. In this study, we examined the effect of four external factors, namely aiming distance, target size, light condition and colour of the laser beam on the pointing precision.

Results

Thirty participants (15 males and 15 females; age = 23.2 ± 4.3) were asked to aim at the target black circles with different sizes (diameters = 4 mm, 8 mm, 12 mm and 16 mm) from five various distances (2 m, 4 m, 6 m, 8 m and 10 m) at two brightness conditions (i.e., bright and dark) using two different coloured laser pointers (red and green). Three aiming parameters, namely number of hits, duration per hit and pointing precision were measured. Results showed that the aiming parameters were the highest with the aiming distance of 2 m and the use of green laser pointer towards larger target sizes regardless of the environmental brightness. Among all factors, aiming distance was the most important external factor that could influence pointing precision.
Plasma Neuron-Specific Enolase is not a reliable biomarker for staging Trypanosoma brucei rhodesiense sleeping sickness patients
Authors: Kato Charles D. , Twesigye Dorothy , Alibu Vincent P. , Nanteza Ann , Nsubuga Julius , Mugasa Claire M. , Matovu Enock
Published: March 2022

Objective

Currently, the only available staging criterion for T. b. rhodesiense requires a lumber puncture to collect and later examine cerebrospinal fluid (CSF). This study examined the potential of plasma Neuron-Specific Enolase (NSE) in discriminating between early and late-stage patients.

Results

When median NSE levels were compared between early and late-stage patients, results showed a significant (P < 0.02) upregulation among late-stage patients (599.8 ng/mL). No significant differences (P > 0.9) in NSE levels were observed between early-stage patients (300 ng/mL) and controls (454 ng/mL). We used Receiver Operator Characteristic (ROC) curves to explore the likelihood of using plasma NSE as a potential stage biomarker in discriminating between early and late-stage HAT patients. Our results showed that NSE demonstrated an area under the curve (AUC) of 0.702 (95% CI 0.583–0.830). A high staging accuracy for NSE was obtained by using a cutoff of > 346.5 ng/mL with a sensitivity of 68.6% (95% CI 55–79.7%) and a specificity of 93.3% (95% CI 70.2–99.7%). Although our results demonstrate that plasma NSE is upregulated in T. b. rhodesiense sleeping sickness patients, its value in discriminating between late and early-stage patients is limited. However, future studies could consider improving its specificity by combining it with other identified plasma biomarkers.
Levothyroxine dosages during pregnancy among hypothyroid women. An experience from a tertiary care center of Karachi, Pakistan, based on data from Maternal Hypothyroidism on Pregnancy Outcomes Study (MHPO-5)
Authors: Kiran Zareen , Khalid Wardah , Sheikh Aisha , Islam Najmul
Published: March 2022

Objectives

The dosage of levothyroxine (LT4) during pregnancy differs among different ethnic groups worldwide. These differences are due to variations in geographical iodine distribution, autoimmunity, and variations in thyrotropin (TSH) targets for pregnancy. To the best of our knowledge, we report the levothyroxine dosage prescribed during pregnancy in hypothyroid women, for the first time from Pakistan.

Results

Levothyroxine dosage of 280 hypothyroid women during pregnancy were reviewed. The median LT4 dosages prescribed before conception was 85.7 mcg per day which increased by 14.3 mcg per day in the first trimester (P 0.001). A significant difference in dosage was observed between controlled and uncontrolled TSH groups in the first trimester (P 0.05). Lower LT4 dosage was prescribed for subclinical hypothyroid women as compared to overt hypothyroid cases, whereas dosages did not differ according to autoimmune status in the latter part of gestation.
Extrapulmonary tuberculosıs: an old but resurgent problem
Authors: Baykan Ali H. , Sayiner Hakan S. , Aydin Elcin , Koc Mustafa , Inan Ibrahim , Erturk Sukru M.
Published: March 2022

Tuberculosis (TB) primarily affects the lungs, but some of its most devastating clinical consequences arise because of its ability to spread from the lungs to other organs. Extrapulmonary TB (EPTB) constitutes 15–20% of all TB cases. Imaging findings are not always specific and can mimic many diseases; therefore, EPTB should be considered in the differential diagnosis, particularly in patients with immune system disorders (AIDS, patients receiving chemotherapy, etc.) and those in other high-risk groups including people with diabetes. The bacterium's passage to the regional lymph nodes is essential for developing a protective T-cell-mediated immune response, but the bacterium can spread hematologically and via the lymphatic system, leading to extrapulmonary involvement. Diagnosis of EPTB in high-risk patients is made based on suspected clinical and radiological findings, but further positive culture and histopathological confirmation may be required in some instances. Radiological evaluations are critical for diagnosis and crucial in planning the treatment and follow-up. This paper aims to review the typical and atypical imaging features and the differential diagnosis of EPTB.
Impact of a radiological protection campaign in emergency paediatric radiology: a multicentric observational study in Brazil
Authors: Oliveira Bernardo Mônica , Morgado Flávio , dos Santos Alair Augusto Sarmet Moreira Damas , Foley Shane , Paulo Graciano , de Almeida Fernando Antônio
Published: March 2022

Purpose

To evaluate the impact of a paediatric radiological protection campaign, implemented in the emergency units of a healthcare provider network in Brazil. This campaign aimed to promote awareness among emergency department physicians, regarding justification of paediatric X-ray referrals for paranasal sinus, chest and CT exams, as a strategy to reduce exposure to ionising radiation.

Method

Frequency analysis of common paediatric imaging referrals from 19 emergency departments was performed for a 3-year period (2015–2018) to coincide with before, during and after the implementation of the radiation protection campaign. The campaign was multifaceted and involved dissemination of educational materials and imaging referral guidelines along with quarterly meetings with participating centres' leaderships. Additionally, patient dose cards were distributed to patients/carers. The Chi-Square test was used to examine the association between the type of examination and the patient's age group. Exact-Fisher test was performed to check for an association between participant engagement and the existence of the radiation protection committee.

Results

Referrals reduced by 25% following the campaign with no reports of misdiagnosis. Many referrals in the youngest age groups. In 15 units, a radiological protection committee was created to raise awareness and to create a multi professional team to communicate the risks and benefits of radiological procedure in children.

Conclusion

The campaign resulted in a substantial reduction in radiological referrals while promoting a radiation protection culture. Simple education initiatives can contribute to savings in both finances and radiation doses, particularly important in radiosensitive cohorts.
Genetic correction of concurrent α- and β-thalassemia patient-derived pluripotent stem cells by the CRISPR-Cas9 technology
Authors: Li Lingli , Yi Hongyan , Liu Zheng , Long Ping , Pan Tao , Huang Yuanhua , Li Yongsheng , Li Qi , Ma Yanlin
Published: March 2022

Background

Thalassemia is a genetic blood disorder characterized by decreased hemoglobin production. Severe anemia can damage organs and severe threat to life safety. Allogeneic transplantation of bone marrow-derived hematopoietic stem cell (HSCs) at present represents a promising therapeutic approach for thalassemia. However, immune rejection and lack of HLA-matched donors limited its clinical application. In recent years, human-induced pluripotent stem cells (hiPSCs) technology offers prospects for autologous cell-based therapy since it could avoid the immunological problems mentioned above.

Methods

In the present study, we established a new hiPSCs line derived from amniotic cells of a fetus with a homozygous β41-42 (TCTT) deletion mutation in the HBB gene and a heterozygous Westmead mutation (C > G) in the HBA2 gene. We designed a CRISPR-Cas9 to target these casual mutations and corrected them. Gene-corrected off-target analysis was performed by whole-exome capture sequencing. The corrected hiPSCs were analyzed by teratoma formation and erythroblasts differentiation assays.

Results

These mutations were corrected with linearized donor DNA through CRISPR/Cas9-mediated homology-directed repair. Corrections of hiPSCs were validated by sequences. The corrected hiPSCs retain normal pluripotency. Moreover, they could be differentiated into hematopoietic progenitors, which proves that they maintain the multilineage differentiation potential.

Conclusions

We designed sgRNAs and demonstrated that these sgRNAs facilitating the CRISPR-Cas9 genomic editing system could be applied to correct concurrent α- and β-thalassemia in patient-derived hiPSCs. In the future, these corrected hiPSCs can be applied for autologous transplantation in patients with concurrent α- and β-thalassemia.
Adipose-derived stem cells ameliorate atopic dermatitis by suppressing the IL-17 expression of Th17 cells in an ovalbumin-induced mouse model
Authors: Guan Jingyan , Li Yibao , Lu Feng , Feng Jingwei
Published: March 2022

Background

Mesenchymal stem cells (MSCs) have therapeutic potential for atopic dermatitis (AD) owing to their immunoregulatory effects. However, the underlying mechanisms associated with the therapeutic efficacy of MSCs on AD are diverse and related to both cell type and delivery method.

Objectives

This study investigated the therapeutic effect and mechanisms of adipose-derived stem cells (ADSCs) on AD using an ovalbumin (OVA)-induced AD mouse model.

Methods

AD mice were subcutaneously injected with mouse ADSCs, cortisone, or PBS, and the therapeutic effects were determined by gross and histological examinations and serum IgE levels. Additionally, qPCR, RNA-sequencing analyses of skin samples and co-culture of ADSCs and Th17 cells were conducted to explore the underlying therapeutic mechanisms.

Results

ADSCs treatment attenuated the AD pathology, decreased the serum IgE levels, and decreased mast cells infiltration in the skin of the model mice. Moreover, tissue levels of IL-4R and Th17-relevant products (IL-17A, CCL20, and MMP12) were suppressed in the ADSC- and cortisone-treated groups. Genomics and bioinformatics analyses demonstrated significant enrichment of inflammation-related pathways in the downregulated genes of the ADSC- and cortisone-treated groups, specifically the IL-17 signaling pathway. Co-culture experiments revealed that ADSCs significantly suppressed the proliferation of Th17 cells and the expression of proinflammatory cytokines (IL-17A and RORγT). Furthermore, expression levels of PD-L1, TGF-β, and PGE2 were significantly upregulated in co-cultured ADSCs relative to those in monocultured ADSCs.

Conclusion

ADSCs ameliorate OVA-induced AD in mice mainly by downregulating IL-17 secretion of Th17 cells.
Cardiovascular disease (CVD) risk assessment of HIV medication regimens using hematopoietic CD34+ progenitor cells
Authors: Elzarki Adrian Farid , Nandula Seshagiri Rao , Awal Hassan , Simon Gary L. , Sen Sabyasachi
Published: March 2022

Background

To determine the effects of integrase inhibitor (INSTI) in comparison with non-INSTI-based regimens such as non-nucleoside reverse transcriptase inhibitors (NNRTIs)-based regimens on cardiovascular disease (CVD) risk in HIV+ patients without overt history of CVD or diabetes, with normal CD4:CD8 count. For CVD risk assessment we primarily used hematopoietic CD34+ progenitor cells, as a biomarker.

Methods

Nineteen male subjects, ages 32–61 years with BMI 21.0–36.0, were enrolled. This was a single time point, cross-sectional, observational study. Subjects were enrolled under 2 groups (either on INSTI-based regimen with 13 subjects or NNRTI (non-INSTI)-based regimens with 6 subjects) who were taking stable doses of HAART. The medication regimens were a combination of one NRTI (typically tenofovir–emtricitabine) plus one INSTI or NNRTI. Our outcome measures were focused on cardiovascular and endothelial cell function and systemic inflammation. Our primary outcome measures were peripheral blood-derived hematopoietic progenitor cell number (CD34 and CD133 positive), CD34+ cell function and gene expression studies. Our secondary outcomes were arterial stiffness measures and serum-based markers of inflammation.

Results

A significant increase in percentage number of progenitor cells, CD133+ cells (p = 0.004), was noted along with an increase of double progenitor mark positive CD133+/CD34+ progenitor cell population being observed in INSTI group as compared to NNRTI group, by flow cytometry. mRNA gene expression for antioxidant gene catalase was noted along with a trend toward a decrease in gene expression of inflammatory marker IL6 (p = 0.06) being observed in CD34+ from INSTI group vs NNRTI group. The plasma IL-6 and CRP levels did not change significantly between the groups. Neutrophil–Lymphocyte ratio (NLR), an important marker of inflammation, was noted to be lower in INSTI group. A mean fasting glucose level was also lower in the INSTI group compared to NNRTI group (p = 0.03). Interestingly, urine microalbumin levels were higher in the INSTI group compared to NNRTI group (p = 0.08), while eGFR levels were significantly lower in the INSTI group (p = 0.002). The arterial stiffness measures did not show statistically significant differences between the two groups.

Conclusion

We conclude that the INSTI regimen may provide a better CVD risk profile compared to NNRTI-based HAART regimen; however, the increased albuminuria along with lower eGFR, noted in INSTI group, is of concern. Because of the small size, these results would need replication in additional studies before changing clinical practice.

Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03782142?cond=Hiv&spons=Sabyasachi+sen&cntry=US&state=US%3ADC&city=Washington&draw=2&rank=1. ClinicalTrials.gov Identifier: NCT03782142.
Regulation of paternal 5mC oxidation and H3K9me2 asymmetry by ERK1/2 in mouse zygotes
Authors: Chen Baobao , Deng Mingtian , Pan Meng-Hao , Sun Shao-Chen , Liu Honglin
Published: March 2022

Background

Extracellular-signal-regulated kinase (ERK) direct cell fate determination during the early development. The intricate interaction between the deposition of H3K9me2, de novo 5mC, and its oxides affects the remodeling of zygotic epigenetic modification. However, the role of fertilization-dependent ERK in the first cell cycle during zygotic reprogramming remains elusive.

Methods

In the present study, we used the small molecule inhibitor to construct the rapid ERK1/2 inactivation system in early zygotes in mice. The pronuclear H3K9me2 deposition assay and the pre-implantation embryonic development ability were assessed to investigate the effect of fertilization-dependent ERK1/2 on zygotic reprogramming and developmental potential. Immunofluorescence and RT-PCR were performed to measure the 5mC or its oxides and H3K9me2 deposition, and the expression of related genes.

Results

We reported that zygotic ERK1/2 inhibition impaired the development competence of pre-implantation embryos. Following the ERK1/2 inhibition, H3K9me2, as well as 5mC and its oxides, were all accumulated abnormally, and the excess accumulation of paternal H3K9me2 and 5mC resulted in reduced asymmetry between parental pronuclei. Furthermore, ERK1/2 inhibition triggered paternal pronuclear localization of the H3K9 methyltransferase G9a and Tet methylcytosine dioxygenase 3 (Tet3). Moreover, the excess localization of G9a antagonized the tight binding of Tet3 to paternal chromatin when ERK1/2 was inhibited.

Conclusions

In conclusion, we propose that zygotic H3K9me2 and 5mC are regulated by fertilization-dependent ERK1/2, which contributes to the development competence of pre-implantation embryos in mice.