bluuebunny/crossref_metadata_2025 huggingface dataset:
Up-regulation of ACE2, the SARS-CoV-2 receptor, in asthmatics on maintenance inhaled corticosteroids
Authors: O’Beirne Sarah L. , Salit Jacqueline , Kaner Robert J. , Crystal Ronald G. , Strulovici-Barel Yael
Published: July 2021

Background

The first step in SARS-CoV-2 infection is binding of the virus to angiotensin converting enzyme 2 (ACE2) on the airway epithelium. Asthma affects over 300 million people world-wide, many of whom may encounter SARS-CoV-2. Epidemiologic data suggests that asthmatics who get infected may be at increased risk of more severe disease. Our objective was to assess whether maintenance inhaled corticosteroids (ICS), a major treatment for asthma, is associated with airway ACE2 expression in asthmatics.

Methods

Large airway epithelium (LAE) of asthmatics treated with maintenance ICS (ICS+), asthmatics not treated with ICS (ICS−), and healthy controls (controls) was analyzed for expression of ACE2 and other coronavirus infection-related genes using microarrays.

Results

As a group, there was no difference in LAE ACE2 expression in all asthmatics vs controls. In contrast, subgroup analysis demonstrated that LAE ACE2 expression was higher in asthmatics ICS+ compared to ICS‾ and ACE2 expression was higher in male ICS+ compared to female ICS+ and ICS‾ of either sex. ACE2 expression did not correlate with serum IgE, absolute eosinophil level, or change in FEV1 in response to bronchodilators in either ICS− or ICS+.

Conclusion

Airway ACE2 expression is increased in asthmatics on long-term treatment with ICS, an observation that should be taken into consideration when assessing the use of inhaled corticosteroids during the pandemic.
A novel large animal model of smoke inhalation-induced acute respiratory distress syndrome
Authors: Leiphrakpam Premila D. , Weber Hannah R. , McCain Andrea , Matas Roser Romaguera , Duarte Ernesto Martinez , Buesing Keely L.
Published: July 2021

Background

Acute respiratory distress syndrome (ARDS) is multifactorial and can result from sepsis, trauma, or pneumonia, amongst other primary pathologies. It is one of the major causes of death in critically ill patients with a reported mortality rate up to 45%. The present study focuses on the development of a large animal model of smoke inhalation-induced ARDS in an effort to provide the scientific community with a reliable, reproducible large animal model of isolated toxic inhalation injury-induced ARDS.

Methods

Animals (n = 21) were exposed to smoke under general anesthesia for 1 to 2 h (median smoke exposure = 0.5 to 1 L of oak wood smoke) after the ultrasound-guided placement of carotid, pulmonary, and femoral artery catheters. Peripheral oxygen saturation (SpO2), vital signs, and ventilator parameters were monitored throughout the procedure. Chest x-ray, carotid, femoral and pulmonary artery blood samples were collected before, during, and after smoke exposure. Animals were euthanized and lung tissue collected for analysis 48 h after smoke inhalation.

Results

Animals developed ARDS 48 h after smoke inhalation as reflected by a decrease in SpO2 by approximately 31%, PaO2/FiO2 ratio by approximately 208 (50%), and development of bilateral, diffuse infiltrates on chest x-ray. Study animals also demonstrated a significant increase in IL-6 level, lung tissue injury score and wet/dry ratio, as well as changes in other arterial blood gas (ABG) parameters.

Conclusions

This study reports, for the first time, a novel large animal model of isolated smoke inhalation-induced ARDS without confounding variables such as cutaneous burn injury. Use of this unique model may be of benefit in studying the pathophysiology of inhalation injury or for development of novel therapeutics.
Genetic evidence for a causative effect of airflow obstruction on left ventricular filling: a Mendelian randomisation study
Authors: Harbaum Lars , Hennigs Jan K. , Simon Marcel , Oqueka Tim , Watz Henrik , Klose Hans
Published: July 2021

Background

Observational studies on the general population have suggested that airflow obstruction associates with left ventricular (LV) filling. To limit the influence of environmental risk factors/exposures, we used a Mendelian randomisation (MR) approach based on common genetic variations and tested whether a causative relation between airflow obstruction and LV filling can be detected.

Methods

We used summary statistics from large genome-wide association studies (GWAS) on the ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC) measured by spirometry and the LV end-diastolic volume (LVEDV) as assessed by cardiac magnetic resonance imaging. The primary MR was based on an inverse variance weighted regression. Various complementary MR methods and subsets of the instrument variables were used to assess the plausibility of the findings.

Results

We obtained consistent evidence in our primary MR analysis and subsequent sensitivity analyses that reducing airflow obstruction leads to increased inflow to the LV (odds ratio [OR] from inverse variance weighted regression 1.05, 95% confidence interval [CI] 1.01–1.09, P = 0.0172). Sensitivity analyses indicated a certain extent of negative horizontal pleiotropy and the estimate from biased-corrected MR-Egger was adjusted upward (OR 1.2, 95% CI 1.09–1.31, P < 0.001). Prioritisation of single genetic variants revealed rs995758, rs2070600 and rs7733410 as major contributors to the MR result.

Conclusion

Our findings indicate a causal relationship between airflow obstruction and LV filling in the general population providing genetic context to observational associations. The results suggest that targeting (even subclinical) airflow obstruction can lead to direct cardiac improvements, demonstrated by an increase in LVEDV. Functional annotation of single genetic variants contributing most to the causal effect estimate could help to prioritise biological underpinnings.
Evaluation of testicular glycogen storage, FGF21 and LDH expression and physiological parameters of sperm in hyperglycemic rats treated with hydroalcoholic extract of Securigera Securidaca seeds, and Glibenclamide
Authors: Babaei Mohammad , Alizadeh-Fanalou Shahin , Nourian Alireza , Yarahmadi Sahar , Farahmandian Navid , Nabi-Afjadi Mohsen , Alipourfard Iraj , Bahreini Elham
Published: July 2021

Structural and physiological changes in sperm and semen parameters reduce fertility in diabetic patients.Securigera Securidaca(S. Securidaca) seed is a herbal medicine with hypoglycemic, antioxidant, and anti-hypertensive effects. The question now is whether this herbal medicine improves fertility in diabetic males. The study aimed to evaluate the effects of hydroalcoholic extract of S. Securidaca seeds (HESS), glibenclamide and a combination of both on fertility in hyperglycemic rats by comparing histological and some biochemical changes in testicular tissue and sperm parameters. The treatment protocol included administration of three doses of HESS and one dose of glibenclamide, as well as treatment with both in diabetic Wistar diabetic rats and comparison of the results with untrated groups. The quality of the testicular tissue as well as histometric parameters and spermatogenesis indices were evaluated during histopathological examination. Epididymal sperm analysis including sperm motility, viability, abnormalities, maturity, and chromatin structure were studied. The effect of HESS on the expression of LDH and FGF21 genes and tissue levels of glycogen, lactate, and total antioxidant capacity in testicular tissue was investigated and compared with glibenclamide. HESS improved sperm parameters in diabetic rats but showed little restorative effect on damaged testicular tissue. In this regard, glibenclamide was more effective than the highest dose of HESS and its combination with HESS enhanced its effectiveness so that histological tissue characteristics and sperm parameters were were comparable to those of healthy rats. The expression level of testicular FGF21 gene increased in diabetic rats, which intensified after treatment with HESS as well as glibenclamide. The combination of HESS and glibenclamide restored the expression level of testicular LDH gene, as well as tissue storage of glycogen, lactate and LDH activity, and serum testosterone to the levels near healthy control. S. Securidaca seeds can be considered as an effective supplement in combination with hypoglycemic drugs to prevent infertility complications in diabetes.
Health technology assessment in sub-Saharan Africa: a descriptive analysis and narrative synthesis
Authors: Hollingworth Samantha , Fenny Ama Pokuaa , Yu Su-Yeon , Ruiz Francis , Chalkidou Kalipso
Published: July 2021

Background

Countries in Sub-Saharan Africa (SSA) are moving towards universal health coverage. The process of Health Technology Assessment (HTA) can support decisions relating to benefit package design and service coverage. HTA involves institutional cooperation with agreed methods and procedural standards. We systematically reviewed the literature on policies and capacity building to support HTA institutionalisation in SSA.

Methods

We systematically reviewed the literature by searching major databases (PubMed, Embase, etc.) until June 2019 using terms considering three aspects: HTA; health policy, decision making; and SSA. We quantitatively extracted and descriptively analysed content and conducted a narrative synthesis eliciting themes from the selected literature, which varied in study type and apporach.

Results

Half of the 49 papers identified were primary research studies and mostly qualitative. Five countries were represented in six of ten studies; South Africa, Ghana, Uganda, Cameroon, and Ethiopia. Half of first authors were from SSA. Most informants were policy makers. Five themes emerged: (1) use of HTA; (2) decision-making in HTA; (3) values and criteria for setting priority areas in HTA; (4) involving stakeholders in HTA; and (5) specific examples of progress in HTA in SSA. The first one was the main theme where there was little use of evidence and research in making policy. The awareness of HTA and economic evaluation was low, with inadequate expertise and a lack of local data and tools.

Conclusions

Despite growing interest in HTA in SSA countries, awareness remains low and HTA-related activities are uncoordinated and often disconnected from policy. Further training and skills development are needed, firmly linked to a strategy focusing on strengthening within-country partnerships, particularly among researchers and policy makers. The international community has an important role here by supporting policy- relevant technical assistance, highlighting that sustainable financing demands evidence-based processes for effective resource allocation, and catalysing knowledge-sharing opportunities among countries facing similar challenges.
Hepatitis E virus prevalence among blood donors in Dali, China
Authors: Fu Ping , Lin Baochai , Wu Bingting , Ke Ling , Yang Tianfu , Du Yue’e , Cheng Lishan , Li Zhou , Li Tiancheng , Liu Yu
Published: July 2021

Background

Hepatitis E virus (HEV) is a nonenveloped RNA virus causing hepatitis E worldwide. The increase in transfusion-transmitted cases of HEV infections from asymptomatic blood donors causing serious illnesses among immunosuppressed recipients has been reported in the past few years. China is one of the most prevalent regions of HEV; as a result, it is important to evaluate the risk of transfusion-transmitted HEV.

Methods

A total of 1864 serum samples (including demographic characteristics) from blood donors were randomly collected from February to March 2018 in Dali city. Anti-HEV IgG, IgM and IgA antibodies and HEV antigen were examined by enzyme-linked immunosorbent assay (ELISA). HEV RNA was detected by real-time PCR. Multivariable logistic regression modelling was used to examine the risk factors associated with HEV prevalence.

Results

Overall, the positive rates of anti-HEV IgG, IgM, and IgA antibodies were 13.36% (249/1864), 1.13% (21/1864), and 1.82% (34/1864), respectively. However, none of the 1864 serum samples were HEV antigen positive or HEV RNA positive. Females (16.69%) had a significantly higher HEV seroprevalence than males (13.04%) (odds ratio [OR] 1.34 [95% CI, 1.02–1.75]). Bai (18.85%) donors had a significantly higher HEV seroprevalence than Han (12.21%) blood donors (odds ratio [OR], 1.65 [95% CI, 1.24–2.19] for Bai).

Conclusions

HEV showed a seroprevalence among blood donors in Yunnan Province, some of which were even recent infections, indicating a threat to the safety of blood transfusions. Whether to formulate a strategy for HEV screening in blood centres needs further research.
The mystery of claustral neural circuits and recent updates on its role in neurodegenerative pathology
Authors: Nikolenko Vladimir N. , Rizaeva Negoriya A. , Beeraka Narasimha M. , Oganesyan Marine V. , Kudryashova Valentina A. , Dubovets Alexandra A. , Borminskaya Irina D. , Bulygin Kirill V. , Sinelnikov Mikhail Y. , Aliev Gjumrakch
Published: July 2021

Introduction

The claustrum is a structure involved in formation of several cortical and subcortical neural microcircuits which may be involved in such functions as conscious sensations and rewarding behavior. The claustrum is regarded as a multi-modal information processing network. Pathology of the claustrum is seen in certain neurological disorders. To date, there are not enough comprehensive studies that contain accurate information regarding involvement of the claustrum in development of neurological disorders.

Objective

Our review aims to provide an update on claustrum anatomy, ontogenesis, cytoarchitecture, neural networks and their functional relation to the incidence of neurological diseases.

Materials and methods

A literature review was conducted using the Google Scholar, PubMed, NCBI MedLine, and eLibrary databases.

Results

Despite new methods that have made it possible to study the claustrum at the molecular, genetic and epigenetic levels, its functions and connectivity are still poorly understood. The anatomical location, relatively uniform cytoarchitecture, and vast network of connections suggest a divergent role of the claustrum in integration and processing of input information and formation of coherent perceptions. Several studies have shown changes in the appearance, structure and volume of the claustrum in neurodegenerative diseases, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), autism, schizophrenia, and depressive disorders. Taking into account the structure, ontogenesis, and functions of the claustrum, this literature review offers insight into understanding the crucial role of this structure in brain function and behavior.
Compliance with the ISO 27020:2019 norm of a sample of currently available preadjusted Orthodontic bracket systems. Are the actual dimensions as expected?
Authors: Bernés Martínez Laura , Garcovich Daniele , España Pamplona Pilar , Adobes Martín Milagros Adobes , Alvarado Lorenzo Alfonso
Published: July 2021

Background

Determine the exact slot dimension of a sample of a MBT prescription stainless steel conventional brackets from different manufacturers to compare the actual values with the nominal ones declared by the manufacturers and to verify the compliance with tolerance limits given by the ISO 27020:2019. Different batches from each manufacturer were evaluated to determine whether or not they are different in size. In addition, the geometry of the slot walls was assessed.

Methods

360 stainless steel preadjusted orthodontic brackets of 12 different manufacturers were assessed. All brackets had a nominal slot size of 0.022 by 0.028 inches, belonged to the right upper central incisor, and were fabricated with the metal injection molding technique (MIM). For each manufacturer, three different manufacturing batches were evaluated. Brackets were coded using a single-blind design.

Results

All bracket systems in the study group except one displayed a statistically significant difference with the nominal declared value, although only four of the systems did not comply with the tolerance limits established by the ISO 27020:2019. In most of the systems, the slot height was oversized when compared to the nominal one. A significant interbatch variability was found in most of the evaluated systems. Most of the brackets walls were divergent.

Conclusions

The dimensional accuracy of commercially available metal brackets is not guaranteed. The respect for the norm should be enforced as well as the quality controls along the manufacturing process since orthodontic brackets are a precision medical device.
High-risk factors for subjective discomfort due to lower limb discrepancy after medial open wedge high tibial osteotomy
Authors: He Axiang , Wang Yin , Chen Yanan , Zhou Ying , Zhang Hui , Mao Yanjie , Liu Wanjun , Zhang Xianlong
Published: July 2021

Background

Medial open wedge high tibial osteotomy (OWHTO) may result in lower limb discrepancy (LLD), and some patients experience uncomfortable symptoms. Studies have found that the degree of LLD is one but not the only high-risk factor for inducing symptoms. The main purpose of this study is to explore the risk factors for symptomatic LLD.

Methods

Sixty-four patients who underwent OWHTO in our hospital between June 2018 and January 2020 were included in the study. Changes in tibia length, lower limb length, femorotibial angle (FTA), LLD, and KOOS score were evaluated before and 1 year after surgery. Questionnaire was used to investigate whether patients had uncomfortable symptoms of LLD after surgery. Binary logistic regression was applied to analyze the risk factors of symptomatic LLD.

Results

There were 18 patients with subjective LLD uncomfortableness, 13 of them were occasional and 5 were frequent. Patients had a mean correction angle of 11.7° ± 4.6°, with a mean increase in tibial length of 6.0 ± 3.5 mm, lower limb length of 7.5 ± 2.3 mm, and LLD of 6.9 ± 4.2 mm at 1 year post-operation. Preoperative and postoperative changes in tibia length and lower limb length were statistically significant (P < 0.0001).There were statistically significant differences in pain, symptoms, ADL, sports/recreations, QOL of KOOS subclassification before and after surgery (P < 0.0001). Binary logistic regression revealed that age ≥ 55, BMI ≥ 28, and LLD ≥ 10 mm were high-risk factors for symptomatic LLD (P = 0.031, OR = 4.82; P = 0.012, OR = 6.251; P = 0.006, OR = 6.836).

Conclusion

Patients with age ≥ 55, BMI ≥ 28, and postoperative LLD ≥ 10 mm are more likely to develop symptomatic LLD. Older or heavier patients, who are expected to have an LLD greater than 10 mm after OWHTO should be fully informed of the possibility of postoperative LLD symptoms.
Common and mutation specific phenotypes of KRAS and BRAF mutations in colorectal cancer cells revealed by integrative -omics analysis
Authors: Kundu Snehangshu , Ali Muhammad Akhtar , Handin Niklas , Conway Louis P. , Rendo Veronica , Artursson Per , He Liqun , Globisch Daniel , Sjöblom Tobias
Published: July 2021

Background

Genes in the Ras pathway have somatic mutations in at least 60 % of colorectal cancers. Despite activating the same pathway, theBRAFV600E mutation and the prevalent mutations in codon 12 and 13 ofKRAShave all been linked to different clinical outcomes, but the molecular mechanisms behind these differences largely remain to be clarified.

Methods

To characterize the similarities and differences between common activatingKRASmutations and betweenKRASandBRAFmutations, we used genome editing to engineerKRASG12C/D/V and G13D mutations in colorectal cancer cells that had their mutantBRAFV600E allele removed and subjected them to transcriptome sequencing, global proteomics and metabolomics analyses.

Results

By intersecting differentially expressed genes, proteins and metabolites, we uncovered (i) two-fold more regulated genes and proteins when comparingKRAStoBRAFmutant cells to those lacking Ras pathway mutation, (ii) five differentially expressed proteins inKRASmutants compared to cells lacking Ras pathway mutation (IFI16, S100A10, CD44, GLRX and AHNAK2) and 6 (CRABP2, FLNA, NXN, LCP1, S100A10 and S100A2) compared toBRAFmutant cells, (iii) 19 proteins expressed differentially in aKRASmutation specific manner versusBRAFV600E cells, (iv) regulation of the Integrin Linked Kinase pathway byKRASbut notBRAFmutation, (v) regulation of amino acid metabolism, particularly of the tyrosine, histidine, arginine and proline pathways, the urea cycle and purine metabolism by Ras pathway mutations, (vi) increased free carnitine inKRASandBRAFmutant RKO cells.

Conclusions

This comprehensive integrative -omics analysis confirms known and adds novel genes, proteins and metabolic pathways regulated by mutantKRASandBRAFsignaling in colorectal cancer. The results from the new model systems presented here can inform future development of diagnostic and therapeutic approaches targeting tumors withKRASandBRAFmutations.
Lower leg muscle structure and function are altered in long‐distance runners with medial tibial stress syndrome: a case control study
Authors: Mattock Joshua , Steele Julie R. , Mickle Karen J.
Published: July 2021

Background

Medial tibial stress syndrome (MTSS) is a common lower leg injury experienced by runners. Although numerous risk factors are reported in the literature, many are non‐modifiable and management of the injury remains difficult. Lower leg muscle structure and function are modifiable characteristics that influence tibial loading during foot‐ground contact. Therefore, this study aimed to determine whether long‐distance runners with MTSS displayed differences in in vivo lower leg muscle structure and function than matched asymptomatic runners.

Methods

Lower leg structure was assessed using ultrasound and a measure of lower leg circumference to quantify muscle cross‐sectional area, thickness and lean lower leg girth. Lower leg function was assessed using a hand‐held dynamometer to quantify maximal voluntary isometric contraction strength and a single leg heel raise protocol was used to measure ankle plantar flexor endurance. Outcome variables were compared between the limbs of long‐distance runners suffering MTSS (n = 20) and matched asymptomatic controls (n = 20). Means, standard deviations, 95 % confidence intervals, mean differences and Cohen's d values were calculated for each variable for the MTSS symptomatic and control limbs.

Results

MTSS symptomatic limbs displayed a significantly smaller flexor hallucis longus cross‐sectional area, a smaller soleus thickness but a larger lateral gastrocnemius thickness than the control limbs. However, there was no statistical difference in lean lower leg girth. Compared to the matched control limbs, MTSS symptomatic limbs displayed deficits in maximal voluntary isometric contraction strength of the flexor hallucis longus, soleus, tibialis anterior and peroneal muscles, and reduced ankle plantar flexor endurance capacity.

Conclusions

Differences in lower leg muscle structure and function likely render MTSS symptomatic individuals less able to withstand the negative tibial bending moment generated during midstance, potentially contributing to the development of MTSS. The clinical implications of these findings suggest that rehabilitation protocols for MTSS symptomatic individuals should aim to improve strength of the flexor hallucis longus, soleus, tibialis anterior and peroneal muscles along with ankle plantar flexor endurance. However, the cross‐sectional study design prevents us determining whether between group differences were a cause or effect of MTSS. Therefore, future prospective studies are required to substantiate the study findings.
Diagnostic workup for endometrioid borderline ovarian tumors (eBOT) requires histopathological evaluation of the uterus
Authors: Reichenbach Juliane , Schmoeckel Elisa , Mahner Sven , Trillsch Fabian
Published: July 2021

Background

For young borderline ovarian tumor (BOT) patients, preservation of the uterus was incorporated as an accepted option into treatment guidelines. For the endometrioid subtype (eBOT) however, adequate histological evaluation is challenging and might be associated with synchronous endometrial disorders or misinterpreted as spread from uterine primaries.

Case presentation

We report the cases of two young patients with eBOT who underwent treatment according to current guidelines. In both cases, unexpected findings of invasive uterine carcinomas were established in final histopathological evaluation.

Conclusions

This constellation highlights the challenging diagnostic workup of BOT and underlines that uterine curettage is indispensable for eBOT to exclude uterine primary tumors when fertility preservation is planned. Accordingly, we suggest to include this procedure into recommendations for diagnostic workup and to state the potential risk in treatment guidelines.
Novel mutation in carnitine palmitoyltransferase 1A detected through newborn screening for a presymptomatic case in China: a case report
Authors: Gan Yi , Yu Fei , Fang Haining
Published: July 2021

Background

Carnitine palmitoyltransferase 1A (CPT1A) deficiency is a rare mitochondrial fatty acid oxidation (FAO) disorder that results in hypoketotic hypoglycemia and hepatic encephalopathy. It is caused by mutation in CPT1A. To date, only two symptomatic cases of CPT1A deficiency have been reported in China.

Case presentation

A newborn male, without any disease-related clinical manifestations, was diagnosed with CPT1A deficiency through newborn screening. Increased free carnitine levels and a significantly increased C0/(C16 + C18) ratio were detected by tandem mass spectrometry, and subsequently, mutations in CPT1A were found by gene sequence analysis. The patient was advised a low-fat, high-protein diet and followed up regularly. During three-years of follow-up since, the patient showed normal growth velocity and developmental milestones. Whole-exome sequence identified two mutations, c.2201 T > C (p.F734S) and c.1318G > A (p.A440T), in the patient. The c.2201 T > C mutation, which has been reported previously, was inherited from his father, while the c.1318G > A, a novel mutation, was inherited from his mother. The amino acid residues encoded by original sequences are highly conserved across different species. These mutations slightly altered the three-dimensional structure of the protein, as analyzed by molecular modeling, suggesting that they may be pathogenic.

Conclusion

This is the first case of CPT1A deficiency detected through newborn screening based on diagnostic levels of free carnitine, in China. Three years follow-up suggested that early diagnosis and diet management may improve the prognosis in CPT1A patient. In addition, we identified a novel mutation c.1318G > A in CPT1A,and a possible unique to Chinese lineage mutation c.2201 T > C. Our findings have expanded the gene spectrum of this rare condition and provided a basis for family genetic counseling and prenatal diagnosis.
Severe hypercalcemia associated with hypophosphatemia in very premature infants: a case report
Authors: Improda Nicola , Mazzeo Francesca , Rossi Alessandro , Rossi Claudia , Improda Francesco Paolo , Izzo Angelo
Published: July 2021

Background

Severe hypercalcemia is rare in newborns; even though often asymptomatic, it may have important sequelae. Hypophosphatemia can occur in infants experiencing intrauterine malnutrition, sepsis and early high-energy parenteral nutrition (PN) and can cause severe hypercalcemia through an unknown mechanism. Monitoring and supplementation of phosphate (PO4) and calcium (Ca) in the first week of life in preterm infants are still debated.

Case presentation

We report on a female baby born at 29 weeks’ gestation with intrauterine growth retardation (IUGR) experiencing sustained severe hypercalcemia (up to 24 mg/dl corrected Ca) due to hypophosphatemia while on phosphorus-free PN. Hypercalcemia did not improve after hyperhydration and furosemide but responded to infusion of PO4. Eventually, the infant experienced symptomatic hypocalcaemia (ionized Ca 3.4 mg/dl), likely exacerbated by contemporary infusion of albumin. Subsequently, a normalization of both parathyroid hormone (PTH) and alkaline phosphatase (ALP) was observed.

Conclusions

Although severe hypercalcemia is extremely rare in neonates, clinicians should be aware of the possible occurrence of this life-threatening condition in infants with or at risk to develop hypophosphatemia. Hypophosphatemic hypercalcemia can only be managed with infusion of PO4, with strict monitoring of Ca and PO4 concentrations.
Plasma glutamine status at intensive care unit admission: an independent risk factor for mortality in critical illness
Authors: Smedberg Marie , Helleberg Johan , Norberg Åke , Tjäder Inga , Rooyackers Olav , Wernerman Jan
Published: July 2021

Background

A plasma glutamine concentration outside the normal range at Intensive Care Unit (ICU) admission has been reported to be associated with an increased mortality rate. Whereas hypoglutaminemia has been frequently reported, the number of patients with hyperglutaminemia has so far been quite few. Therefore, the association between hyperglutaminemia and mortality outcomes was studied in a prospective, observational study.

Patients and methods

Consecutive admissions to a mixed general ICU were eligible. Exclusion criteria were < 18 years of age, readmissions, no informed consent, or a ‘do not resuscitate’ order at admission. A blood sample was saved within one hour from admission to be analysed by high-pressure liquid chromatography for glutamine concentration. Conventional risk scoring (Simplified Acute Physiology Score and Sequential Organ Failure Assessment) at admission, and mortality outcomes were recorded for all included patients.

Results

Out of 269 included patients, 26 were hyperglutaminemic (≥ 930 µmol/L) at admission. The six-month mortality rate for this subgroup was 46%, compared to 18% for patients with a plasma glutamine concentration < 930 µmol/L (P = 0.002). A regression analysis showed that hyperglutaminemia was an independent mortality predictor that added prediction value to conventional admission risk scoring and age.

Conclusion

Hyperglutaminemia in critical illness at ICU admission was an independent mortality predictor, often but not always, associated with an acute liver condition. The mechanism behind a plasma glutamine concentration outside normal range, as well as the prognostic value of repeated measurements of plasma glutamine during ICU stay, remains to be investigated.
Optimization of the feeding rate of Anopheles farauti s.s. colony mosquitoes in direct membrane feeding assays
Authors: Timinao Lincoln , Vinit Rebecca , Katusele Michelle , Schofield Louis , Burkot Thomas R. , Karl Stephan
Published: July 2021

Background

Direct membrane feeding assays (DMFA) are an important tool to study parasite transmission to mosquitoes. Mosquito feeding rates in these artificial systems require optimization, as there are a number of factors that potentially influence the feeding rates and there are no standardized methods that apply to all anopheline species.

Methods

A range of parameters prior to and during direct membrane feeding (DMF) were evaluated for their impact on Anopheles farauti sensu stricto feeding rates, including the starving conditions and duration of starving prior to feeding, membrane type, DMF exposure time, mosquito age, feeding in the light versus the dark, blood volume, mosquito density and temperature of water bath.

Results

The average successful DMFA feeding rate for An. farauti s.s. colony mosquitoes increased from 50 to 85% when assay parameters were varied. Overnight starvation and Baudruche membrane yielded the highest feeding rates but rates were also affected by blood volume in the feeder and the mosquito density in the feeding cups. Availability of water during the pre-feed starvation period did not significantly impact feeding rates, nor did the exposure duration to blood in membrane feeders, the age of mosquitoes (3, 5 and 7 days post-emergence), feeding in the light versus the dark, or the temperature (34 °C, 38 °C, 42 °C and 46 °C) of the water bath.

Conclusion

Optimal feeding conditions in An. farauti s.s. DMFA were to offer 50 female mosquitoes in a cup (with a total surface area of ~ 340 cm2 with 1 mosquito/6.8 cm2) that were starved overnight 350–500 µL of blood (collected in heparin-coated Vacutainer tubes) per feeder in feeders with a surface area ~ 5 cm2 (with a maximum capacity of 1.5 mL of blood) via a Baudruche membrane, for at least 10–20 min.

Graphical Abstract
De novo transcriptome assembly data for sengon (Falcataria moluccana) trees displaying resistance and susceptibility to boktor stem borers (Xystrocera festiva Pascoe)
Authors: Siregar Ulfah J. , Nugroho Aditya , Shabrina Hasyyati , Indriani Fitri , Damayanti Apriliya , Matra Deden D.
Published: July 2021

Objectives

Sengon (Falcataria moluccana) is a popular tree species in community plantation forests in Java, Indonesia due to its fast-growing and multipurpose characteristics. However, without effective control measures sengon plantations are vulnerable to boktor stem borer (Xystrocera festiva) infestation. Previous research found some boktor-resistant trees amid mostly susceptible individuals. Resistant trees have higher levels of enzyme inhibitory activity than susceptible ones. However, efforts to differentiate between the two accessions using microsatellite markers failed to provide satisfactory answers. This dataset was created to study differences in gene expressions between resistant and susceptible accessions, and to identify candidate genes involved in boktor resistance in sengon.

Data description

RNA was extracted from fresh wood samples collected from two individual trees: one heavily infested with boktor larvae, and the other showing no signs of infestation. The sample trees grow in close proximity to each other within the same plantation. The RNA was sequenced using the BGISEQ-500 platform and produced 78.5 million raw reads. De novo transcriptome were assembled using Trinity and produced 96,164 contigs after filtering and clustering. This transcriptome data is important for understanding pest resistance mechanisms in sengon trees, serving as basis for an improvement program for resistance to boktor pest.
Duodenal imaging on the spotlight: from A to Z
Authors: Terra Carolina , Ramos-Andrade Daniel , Sá-Marques Ivo , Brito Jorge , Caseiro-Alves Filipe , Curvo-Semedo Luís
Published: July 2021

Abdominal computed tomography (CT) is frequently performed to evaluate gastrointestinal pathologic conditions. The majority of the gastrointestinal radiology literature has concentrated on the colon, stomach, and distal small bowel. The duodenum is often overlooked on imaging, namely on CT, but its anatomy (intra and retroperitoneal) and location in such close proximity to other viscera results in involvement by a multitude of primary and secondary processes, some of them exclusive to this bowel segment. While some conditions, like duplications, lipomas, and diverticula, are usually asymptomatic and are incidentalomas that have no pathologic significance, others are symptomatic and very relevant and should be recognized by every general radiologist: development conditions such as annular pancreas and gut malrotation; inflammatory processes such as ulcers and secondary involvement from pancreatitis; neoplastic conditions such as adenocarcinoma, lymphoma, or local extension from adjacent malignancies. They all can be reliably diagnosed with CT. In this article, we demonstrate the typical imaging features of various diseases involving the duodenum, such as developmental, traumatic, inflammatory, infectious, neoplastic, and postsurgical pathologic conditions in alphabetical order, focusing mainly on upper gastrointestinal series (UGIS) and CT but also some radiography, ultrasound, and magnetic resonance (MR) imaging.
Rituximab induced acute thrombocytopenia in a patient with systemic lupus erythematosus: a case report
Authors: Yudhishdran Jevon , Sivakumar Jeyalakshmy , Navinan Mitrakrishnan Rayno , Bandapatti Sareesh
Published: July 2021

Background

Rituximab is a novel chimeric monoclonal antibody that has established itself as a potent therapeutic option for autoimmune medical conditions, including systemic lupus erythematosus, owing to its mechanism of action targeting CD20 cells. Rituximab is also known to cause a spectrum of side effects including hematological abnormalities. Acute isolated thrombocytopenia following rituximab is an uncommon occurrence and, when seen, occurs in the presence of underlying hematological malignancies. Its occurrence in autoimmune diseases is rare. Despite this, acute isolated thrombocytopenia in the backdrop of systemic lupus erythematosus is undocumented.

Case presentation

A young 36-year-old South Asian female with systemic lupus erythematosus with class IV lupus nephritis poorly responding to standard therapy was initiated on rituximab. Ten days later, she presented with mucocutaneous bleeding and ecchymotic skin lesions. Isolated severe thrombocytopenia was noted with a platelet count of 5 × 109/L (150–450). Anticipating life-threatening bleeding, she was given intravenous immunoglobulin, methyl prednisolone, and platelet transfusion considering a spectrum of initial differential diagnosis. Rituximab was also withheld. Though extensively investigated, most investigations were negative. A platelet destructive process was suspected as bone marrow biopsy showed adequate megakaryocytes. Weighing the risk versus benefit, following recovery, she was reinitiated on rituximab. Within 4 days, she presented again with similar symptoms and severe isolated thrombocytopenia was noted. Rituximab-induced acute thrombocytopenia was considered the working clinical diagnosis.

Case discussion and conclusion

Rituximab can cause a spectrum of hematological abnormalities, including isolated acute thrombocytopenia. Its occurrence in autoimmune conditions is rare, and its manifestation in systemic lupus erythematosus is undocumented. Its exact etiology is still disputed. Usually considered benign, the platelet numbers tend to show improvement with cessation of therapy. However, in the presence of mucocutaneous bleeding in our patient, we took an aggressive approach to management. Though evidence for corrective therapy is anecdotal, it could be justified on the basis of averting potential catastrophic hemorrhagic manifestations. The spectrum of autoimmune disease that potentially predisposes rituximab to cause thrombocytopenia should be extended to include systemic lupus erythematosus.
Application of mesenchymal stem cell sheet to treatment of ischemic heart disease
Authors: Chang Dehua , Fan Taibing , Gao Shuang , Jin Yongqiang , Zhang Mingkui , Ono Minoru
Published: July 2021

In recent years, mesenchymal stem cells (MSCs) have been used to improve cardiac function and attenuate adverse ventricular remodeling of the ischemic myocardium through paracrine effects and immunoregulation functions. In combination with cell sheet technology, MSCs could be more easily transplanted to the ischemic area. The long-term retention of MSCs in the affected area was realized and significantly improved the curative effect. In this review, we summarized the research and the applications of MSC sheets to the treatment of ischemic heart tissue. At present, many types of MSCs have been considered as multipotent cells in the treatment of heart failure, such as bone marrow-derived mesenchymal stem cells (BM-MSCs), adipose-derived mesenchymal stem cells (AD-MSCs), umbilical cord-derived mesenchymal stem cells (UC-MSCs), and skeletal myoblasts (SMs). Since UC-MSCs have few human leukocyte antigen-II and major histocompatibility complex class I molecules, and are easy to isolate and culture, UC-MSC sheets have been proposed as a candidate for clinical applications to ischemic heart disease.
The tissue origin of human mesenchymal stem cells dictates their therapeutic efficacy on glucose and lipid metabolic disorders in type II diabetic mice
Authors: Ma Yinzhong , Wang Lisha , Yang Shilun , Liu Dongyu , Zeng Yi , Lin Lilong , Qiu Linhui , Lu Jiahao , Chang Junlei , Li Zhihuan
Published: July 2021

Background

The therapeutic efficacy of mesenchymal stem cells (MSCs) of different tissue origins on metabolic disorders can be varied in many ways but remains poorly defined. Here we report a comprehensive comparison of human MSCs derived from umbilical cord Wharton’s jelly (UC-MSCs), dental pulp (PU-MSCs), and adipose tissue (AD-MSCs) on the treatment of glucose and lipid metabolic disorders in type II diabetic mice.

Methods

Fourteen-to-fifteen-week-old male C57BL/6 db/db mice were intravenously administered with human UC-MSCs, PU-MSCs, and AD-MSCs at various doses or vehicle control once every 2 weeks for 6 weeks. Metformin (MET) was given orally to animals in a separate group once a day at weeks 4 to 6 as a positive control. Body weight, blood glucose, and insulin levels were measured every week. Glucose tolerance tests (GTT) and insulin tolerance tests (ITT) were performed every 2 weeks. All the animals were sacrificed at week 6 and the blood and liver tissues were collected for biochemical and histological examinations.

Results

UC-MSCs showed the strongest efficacy in reducing fasting glucose levels, increasing fasting insulin levels, and improving GTT and ITT in a dose-dependent manner, whereas PU-MSCs showed an intermediate efficacy and AD-MSCs showed the least efficacy on these parameters. Moreover, UC-MSCs also reduced the serum low-density lipoprotein cholesterol (LDL-C) levels with the most prominent potency and AD-MSCs had only very weak effect on LDL-C. In contrast, AD-MSCs substantially reduced the lipid content and histological lesion of liver and accompanying biomarkers of liver injury such as serum aspartate transaminase (AST) and alanine aminotransferase (ALT) levels, whereas UC-MSCs and PU-MSCs displayed no or modest effects on these parameters, respectively.

Conclusions

Taken together, our results demonstrated that MSCs of different tissue origins can confer substantially different therapeutic efficacy in ameliorating glucose and lipid metabolic disorders in type II diabetes. MSCs with different therapeutic characteristics could be selected according to the purpose of the treatment in the future clinical practice.
Stem cell therapies for autoimmune hepatitis
Authors: Lotfy Ahmed , Elgamal Aya , Burdzinska Anna , Swelum Ayman A. , Soliman Reham , Hassan Ayman A. , Shiha Gamal
Published: July 2021

Autoimmune hepatitis is a chronic inflammatory hepatic disorder which may cause liver fibrosis. Appropriate treatment of autoimmune hepatitis is therefore important. Adult stem cells have been investigated as therapies for a variety of disorders in latest years. Hematopoietic stem cells (HSCs) were the first known adult stem cells (ASCs) and can give rise to all of the cell types in the blood and immune system. Originally, HSC transplantation was served as a therapy for hematological malignancies, but more recently researchers have found the treatment to have positive effects in autoimmune diseases such as multiple sclerosis. Mesenchymal stem cells (MSCs) are ASCs which can be extracted from different tissues, such as bone marrow, adipose tissue, umbilical cord, and dental pulp. MSCs interact with several immune response pathways either by direct cell-to-cell interactions or by the secretion of soluble factors. These characteristics make MSCs potentially valuable as a therapy for autoimmune diseases. Both ASC and ASC-derived exosomes have been investigated as a therapy for autoimmune hepatitis. This review aims to summarize studies focused on the effects of ASCs and their products on autoimmune hepatitis.
Spatio-temporal model of Meox1 expression control involvement of Sca-1-positive stem cells in neointima formation through the synergistic effect of Rho/CDC42 and SDF-1α/CXCR4
Authors: Wu Yan , Li Yuan-jin , Shi Liu-liu , Liu Yun , Wang Yan , Bao Xin , Xu Wei , Yao Lu-yuan , Mbadhi Magdaleena Naemi , Chen Long , Li Shan , Li Xing-yuan , Zhang Zhi-feng , Zhao Sen , Zhang Ruo-nan , Chen Shi-You , Zhang Jing-xuan , Jun-mingTang
Published: July 2021

Aims

Neointimal hyperplasia remains a major obstacle in vascular regeneration. Sca-1-positive progenitor cells residing within the vascular adventitia play a crucial role in the assemblage of vascular smooth muscle cell (VSMC) and the formation of the intimal lesion. However, the underlying mechanisms during vascular injury are still unknown.

Methods and results

Aneointimal formation rat model was prepared by carotid artery injury using 2F-Forgaty. After vascular injury, Meox1 expressions time-dependently increased during the neointima formation, with its levels concurrently increasing in the adventitia, media, and neointima. Meox1 was highly expressed in the adventitia on the first day after vascular injury compared to the expression levels in the media. Conversely, by the 14th day post-injury, Meox1 was extensively expressed more in the media and neointima than the adventitia. Analogous to the change of Meox1 in injured artery, Sca-1+ progenitor cells increased in the adventitia wall in a time-dependent manner and reached peak levels on the 7th day after injury. More importantly, this effect was abolished by Meox1 knockdown with shRNA. The enhanced expression of SDF-1α after vascular injury was associated with the markedly enhanced expression levels of Sca1+ progenitor cell, and these levels were relatively synchronously increased within neointima by the 7th day after vascular injury. These special effects were abolished by the knockdown of Meox1 with shRNA and inhibition of CXCR4 by its inhibitor, AMD3100. Finally, Meox1 concurrently regulated SDF-1α expressions in VSMC via activating CDC42, and CDC42 inhibition abolished these effects by its inhibitor, ZCL278. Also, Meox1 was involved in activation of the CXCR4 expression of Sca-1+ progenitor cells by CDC42.

Conclusions

Spatio-temporal model of Meox1 expression regulates theSca-1+progenitor cell migration during the formation of the neointima through the synergistic effect of Rho/CDC42 and SDF-1α/CXCR4.
Mesenchymal stem cell therapy ameliorates metabolic dysfunction and restores fertility in a PCOS mouse model through interleukin-10
Authors: Chugh Rishi Man , Park Hang-soo , El Andaloussi Abdeljabar , Elsharoud Amro , Esfandyari Sahar , Ulin Mara , Bakir Lale , Aboalsoud Alshimaa , Ali Mohamed , Ashour Dalia , Igboeli Prosper , Ismail Nahed , McAllister Jan , Al-Hendy Ayman
Published: July 2021

Background

Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in reproductive-age women. Excessive inflammation and elevated androgen production from ovarian theca cells are key features of PCOS. Human bone marrow mesenchymal stem cells (BM-hMSC) and their secreted factors (secretome) exhibit robust anti-inflammatory capabilities in various biological systems. We evaluated the therapeutic efficacy of BM-hMSC and its secretome in both in vitro and in vivo PCOS models.

Methods

For in vitro experiment, we treated conditioned media from BM-hMSC to androgen-producing H293R cells and analyzed androgen-producing gene expression. For in vivo experiment, BM-hMSC were implanted into letrozole (LTZ)-induced PCOS mouse model. BM-hMSC effect in androgen-producing cells or PCOS model mice was assessed by monitoring cell proliferation (immunohistochemistry), steroidogenic gene expression (quantitative real-time polymerase chain reaction [qRT-PCR] and Western blot, animal tissue assay (H&E staining), and fertility by pup delivery.

Results

BM-hMSC significantly downregulate steroidogenic gene expression, curb inflammation, and restore fertility in treated PCOS animals. The anti-inflammatory cytokine interleukin-10 (IL-10) played a key role in mediating the effects of BM-hMSC in our PCOS models. We demonstrated that BM-hMSC treatment was improved in metabolic and reproductive markers in our PCOS model and able to restore fertility.

Conclusion

Our study demonstrates for the first time the efficacy of intra-ovarian injection of BM-hMSC or its secretome to treat PCOS-related phenotypes, including both metabolic and reproductive dysfunction. This approach may represent a novel therapeutic option for women with PCOS. Our results suggest that BM-hMSC can reverse PCOS-induced inflammation through IL-10 secretion. BM-hMSC might be a novel and robust therapeutic approach for PCOS treatment.