Publications by authors named "Prashant Sharma"

394 Publications

Architecture and Composition Dictate Viscoelastic Properties of Organ-Derived Extracellular Matrix Hydrogels.

Polymers (Basel) 2021 Sep 15;13(18). Epub 2021 Sep 15.

Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1 (EA11), 9713 GZ Groningen, The Netherlands.

The proteins and polysaccharides of the extracellular matrix (ECM) provide architectural support as well as biochemical and biophysical instruction to cells. Decellularized, ECM hydrogels replicate in vivo functions. The ECM's elasticity and water retention renders it viscoelastic. In this study, we compared the viscoelastic properties of ECM hydrogels derived from the skin, lung and (cardiac) left ventricle and mathematically modelled these data with a generalized Maxwell model. ECM hydrogels from the skin, lung and cardiac left ventricle (LV) were subjected to a stress relaxation test under uniaxial low-load compression at a 20%/s strain rate and the viscoelasticity determined. Stress relaxation data were modelled according to Maxwell. Physical data were compared with protein and sulfated GAGs composition and ultrastructure SEM. We show that the skin-ECM relaxed faster and had a lower elastic modulus than the lung-ECM and the LV-ECM. The skin-ECM had two Maxwell elements, the lung-ECM and the LV-ECM had three. The skin-ECM had a higher number of sulfated GAGs, and a highly porous surface, while both the LV-ECM and the lung-ECM had homogenous surfaces with localized porous regions. Our results show that the elasticity of ECM hydrogels, but also their viscoelastic relaxation and gelling behavior, was organ dependent. Part of these physical features correlated with their biochemical composition and ultrastructure.
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http://dx.doi.org/10.3390/polym13183113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470996PMC
September 2021

Adipose Tissue-Derived Stromal Cells Alter the Mechanical Stability and Viscoelastic Properties of Gelatine Methacryloyl Hydrogels.

Int J Mol Sci 2021 Sep 21;22(18). Epub 2021 Sep 21.

Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.

The extracellular matrix provides mechanical cues to cells within it, not just in terms of stiffness (elasticity) but also time-dependent responses to deformation (viscoelasticity). In this work, we determined the viscoelastic transformation of gelatine methacryloyl (GelMA) hydrogels caused by adipose tissue-derived stromal cells (ASCs) through mathematical modelling. GelMA-ASCs combination is of interest to model stem cell-driven repair and to understand cell-biomaterial interactions in 3D environments. Immortalised human ASCs were embedded in 5%, 10%, and 15% (/) GelMA hydrogels and evaluated for 14 d. GelMA had a concentration-dependent increase in stiffness, but cells decreased this stiffness over time, across concentrations. Viscoelastic changes in terms of stress relaxation increased progressively in 5% GelMA, while mathematical Maxwell analysis showed that the relative importance () of the fastest Maxwell elements increased proportionally. The 10% GelMA only showed differences at 7 d. In contrast, ASCs in 15% GelMA caused slower stress relaxation, increasing the of the slowest Maxwell element. We conclude that GelMA concentration influenced the stiffness and number of Maxwell elements. ASCs changed the percentage stress relaxation and of Maxwell elements transforming hydrogel viscoelasticity into a more fluid environment over time. Overall, 5% GelMA induced the most favourable ASC response.
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http://dx.doi.org/10.3390/ijms221810153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8468163PMC
September 2021

A randomized controlled trial comparing the efficacy, tolerability, and cost of oral iron preparations in iron-deficiency anemia in pregnancy.

J Obstet Gynaecol Res 2021 Sep 6. Epub 2021 Sep 6.

Department of Pharmacology, Post Graduate Institute of Medical Education & Research, Chandigarh, India.

Objective: To evaluate the efficacy, tolerability, and cost of four commonly prescribed oral iron preparations: ferrous sulfate (FS), ferrous fumarate (FF), ferrous ascorbate (FA), and carbonyl iron (CI) in the treatment of iron-deficiency anemia (IDA) in pregnant women.

Methods: It was a prospective, randomized, open-label, blinded endpoint (PROBE) design with four parallel active control groups: FS, FF, FA, CI. The primary outcome was the proportion of participants becoming non-anemic (Hb ≥ 11 g%) at the end of the study period. The secondary outcomes were the proportion of participants achieving normal red blood corpuscular indices such as mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration; the proportion of participants achieving normal iron indices such as serum iron, serum ferritin, total iron-binding capacity, and transferrin saturation; and comparison of incidence of any adverse events between treatment groups and comparison of costs of individual drug therapy between treatment groups.

Results: One hundred and twenty patients were randomized to four different groups (n = 30). The results of the present study show that all the four iron salts at the dose of 200 mg elemental iron per day were equally effective in improving hemoglobin concentration and other hematological parameters. The adverse effects were more common in the FF group (56.7%). The pharmacoeconomic analysis showed that all the drugs are equally cost-effective.

Conclusion: To conclude from the results of the present study, it can be said that FS, FF, FA, and CI are equally effective in treating IDA and they can be prescribed interchangeably.
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http://dx.doi.org/10.1111/jog.14999DOI Listing
September 2021

Tribological Properties of Micropored Poly(2-hydroxyethyl methacrylate) Hydrogels in a Biomimetic Aqueous Environment.

ACS Appl Mater Interfaces 2021 Sep 27;13(35):41473-41484. Epub 2021 Aug 27.

Department of Mechanical Engineering, Stevens Institute of Technology, Castle Point on Hudson, Hoboken, New Jersey 07030, United States.

The applications of hydrogels in tissue engineering as implants have rapidly grown in the last decade. However, the tribological properties of hydrogels under physiologically relevant conditions, especially those of textured hydrogels, have remained largely unknown due to the complexity of their mechanical and chemical properties. In this study, we experimentally investigated the tribological properties of micopored poly(2-hydroxyethyl methacrylate) (pHEMA) with the lateral pore dimensions varied compared to untextured pHEMA, the most commonly used hydrogel in ophthalmology, under physiologically relevant conditions. The pHEMA specimens were slid against a smooth glass curve under varying loads (6-60 mN, leading to an average contact pressure of 10-21 kPa) and sliding speeds (1-10 mm/s) in phosphate-buffered saline (pH 7.4) at 33 °C to mimic the physiological conditions in human eyes. At relatively low loads and sliding speeds (e.g., 6 mN and 1 mm/s), the micopored pHEMA did not reduce the dissipated frictional energy significantly. However, at relatively high loads and sliding speeds (e.g., 60 mN and 100 mm/s), the micopored pHEMA resulted in significantly lower frictional energy (reduced by up to 68%) dissipation than the untextured pHEMA. The effect was more pronounced with the micropores with smaller dimensions. These are attributed to the greater amount and retentivity of the interfacial fluid supported by the free water squeezed out of the micropores with the smaller dimensions under the higher load and sliding speed. These results suggest that the use of micropore texturing on hydrogels in practice, such as for ocular applications, can be leveraged to reduce friction and wear under physiological conditions and hence lower the chance of inflammation near eye implants or keratoprosthesis.
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http://dx.doi.org/10.1021/acsami.1c13718DOI Listing
September 2021

The genome of a daddy-long-legs (Opiliones) illuminates the evolution of arachnid appendages.

Proc Biol Sci 2021 08 4;288(1956):20211168. Epub 2021 Aug 4.

Department of Integrative Biology, University of Wisconsin-Madison, Madison, 53706 WI, USA.

Chelicerate arthropods exhibit dynamic genome evolution, with ancient whole-genome duplication (WGD) events affecting several orders. Yet, genomes remain unavailable for a number of poorly studied orders, such as Opiliones (daddy-long-legs), which has hindered comparative study. We assembled the first harvestman draft genome for the species , which bears elongate, prehensile appendages, made possible by numerous distal articles called tarsomeres. Here, we show that the genome of exhibits a single Hox cluster and no evidence of WGD. To investigate the developmental genetic basis for the quintessential trait of this group-the elongate legs-we interrogated the function of the Hox genes () and (), and a homologue of (). Knockdown of incurred homeotic transformation of two pairs of legs into pedipalps, with dramatic shortening of leg segments in the longest leg pair, whereas homeosis in L3 is only achieved upon double knockdown. Knockdown of incurred shortened appendages and the loss of tarsomeres. The similarity of loss-of-function phenotypic spectra in insects and this arachnid suggest that repeated cooption of EGFR signalling underlies the independent gains of supernumerary tarsomeres across the arthropod tree of life.
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http://dx.doi.org/10.1098/rspb.2021.1168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8334856PMC
August 2021

A novel ATRX splice variant causing acquired HbH disease in myelodysplastic syndrome with excess blasts-1.

Cancer Genet 2021 Jul 20. Epub 2021 Jul 20.

Department of Hematology, Postgraduate Institute of Medical Education & Research, Chandigarh, India. Electronic address:

A 60-year-old male with myelodysplastic syndrome with excess blasts-1 had unexplained microcytic hypochromic anemia. The cause of his anemia was revealed on supravital staining, hemoglobin studies and next-generation sequencing to be a novel hemizygous potentially pathogenic missense/splice site variant NM_000489.5:c.6848A>C, (p.Lys2283Thr) in exon 31 of the ATRX gene.
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http://dx.doi.org/10.1016/j.cancergen.2021.07.001DOI Listing
July 2021

YouTube™ as an effective but potentially addictive distraction tool for paediatric phlebotomy.

Acta Paediatr 2021 10 30;110(10):2875-2876. Epub 2021 Jul 30.

Department of Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.1111/apa.16044DOI Listing
October 2021

CE-HPLC Derived P2 and P3-Peaks in Health and in Hb D-Punjab and HbE States.

Indian J Hematol Blood Transfus 2021 Jul 8;37(3):503-504. Epub 2020 Oct 8.

Department of Hematology, Postgraduate Institute of Medical Education and Research, Level 5, Research Block A, Sector 12, Chandigarh, 160012 India.

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http://dx.doi.org/10.1007/s12288-020-01363-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239074PMC
July 2021

An Autopsy Case of β-Thalassemia Major Illuminating the Pathological Spectrum of the Disease.

Hemoglobin 2021 May 30;45(3):180-185. Epub 2021 Jun 30.

Department of Pediatrics, Pediatric Hematology-Oncology Unit, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Despite declining rates worldwide, autopsy studies remain invaluable tools to expand existing knowledge on the pathophysiology of diseases, especially those with multisystem involvement. β-thalassemia major (β-TM) is a relatively common hemoglobinopathy in India and is characterized by a regular requirement for life-sustaining transfusions and chelation. The iron overload is an invariable side effect. This secondary hemosiderosis leads to several complications, primarily in the heart, liver, pancreas, and endocrine organs. Despite adequate transfusion and chelation, untransplanted patients may show early mortality for several reasons. We report a 10-year-old boy with β-TM who died with clinical possibilities of iron overload-related cardiac failure and pulmonary arterial hypertension. His autopsy revealed certain unique disease pathologies in the form of minimal cardiac fibrosis in the presence of significant cardiac siderosis and widespread endocrine damage due to iron-overload. A null-cell pituitary microadenoma, previously undescribed in thalassemia syndromes, was found. This report highlights the importance of the diminishing art of autopsy, without which these histopathological insights would not have emerged.
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http://dx.doi.org/10.1080/03630269.2021.1941080DOI Listing
May 2021

Hematological Markers as Predictors of Treatment Outcomes with Lu-177 DOTATATE in Patients with Advanced Neuroendocrine Tumors.

Cancer Biother Radiopharm 2021 Jun 29. Epub 2021 Jun 29.

Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Chronic inflammation has been linked to the development and prognosis of neuroendocrine tumors (NETs). The current study intended to evaluate the role of peripheral hematological inflammatory markers, viz. the platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio, and monocyte-lymphocyte ratio, as predictors of treatment outcomes in patients with advanced NETs after Lu-177 DOTATATE therapy. Data of consecutive patients with advanced metastatic and/or inoperable NETs treated with Lu-177 DOTATATE from the year 2012 to 2019 at the authors' center were retrospectively analyzed. Forty-two NET patients (median age: 49.5 years) received a median cumulative activity of 29.6 GBq of Lu-177 DOTATATE over 2-5 cycles at 8-12-week intervals. The median progression-free survival (PFS) of the study cohort was 30 months (95% confidence interval, CI: 18.2-41.9 months). A baseline PLR ≥173.1 was found to be a significant predictor of poor PFS with a univariate hazard ratio of 3.82 (95% CI: 1.21-12.03); however, the association was not significant on multivariate analysis. The median overall survival was not reached and none of the parameters were significantly associated with it. A higher baseline PLR was shown to be associated with a negative outcome on PFS after Lu-DOTATATE therapy and is a promising marker for future larger studies.
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http://dx.doi.org/10.1089/cbr.2021.0053DOI Listing
June 2021

Pneumatosis cystoides intestinalis associated with novel cancer therapy use.

ANZ J Surg 2021 Jun 18. Epub 2021 Jun 18.

Department of General Surgery, Christchurch Hospital, Canterbury District Health Board, Christchurch, New Zealand.

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http://dx.doi.org/10.1111/ans.17027DOI Listing
June 2021

Implications of a cheliceral axial duplication in Tetragnatha versicolor (Araneae: Tetragnathidae) for arachnid deuterocerebral appendage development.

Dev Genes Evol 2021 Jun 14. Epub 2021 Jun 14.

Department of Integrative Biology, University of Wisconsin-Madison, 441 Birge Hall, 430 Lincoln Drive, Madison, WI, 53706, USA.

The homology of the arachnid chelicera with respect to other head appendages in Panarthropoda has long been debated. Gene expression data and the re-interpretation of early transitional fossils have supported the homology of the deutocerebrum and its associated appendages, implying a homology between primary antennae (mandibulates), chelicerae (euchelicerates), and chelifores (sea spiders). Nevertheless, comparatively little is known about the mechanistic basis of proximo-distal (PD) axis induction in chelicerates, much less the basis for cheliceral fate specification. Here, we describe a new cheliceral teratology in the spider Tetragnatha versicolor Walckenaer, 1841, which consists on a duplication of the PD axis of the left chelicera associated with a terminal secondary schistomely on the fang of the lower axis. This duplication offers clues as to potential shared mechanisms of PD axis formation in the chelicera. We review the state of knowledge on PD axis induction mechanisms in arthropods and identify elements of gene regulatory networks that are key for future functional experiments of appendage development in non-insect model systems. Such investigations would allow a better understanding of PD axis induction of modified and poorly studied arthropod limbs (e.g., chelicerae, chelifores, and ovigers).
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http://dx.doi.org/10.1007/s00427-021-00678-9DOI Listing
June 2021

Nonviral Expression of LL-37 in a Human Skin Equivalent to Prevent Infection in Skin Wounds.

Hum Gene Ther 2021 Oct 5;32(19-20):1147-1157. Epub 2021 Jul 5.

Department of Biomedical Engineering, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Inefficient autologous tissue recovery in skin wounds increases the susceptibility of patients to infections caused by multidrug resistant microorganisms, resulting in a high mortality rate. Genetic modification of skin cells has become an important field of study because it could lead to the construction of more functional skin grafts, through the overexpression of antimicrobial peptides that would prevent early contamination and infection with bacteria. In this study, we produce and evaluate human skin equivalents (HSEs) containing transfected human primary fibroblasts and keratinocytes by polyplexes to express the antimicrobial peptide LL-37. The effect of LL-37 on the metabolic activity of normal HSEs was evaluated before the construction of the transfected HSEs, and the antimicrobial efficacy against and was evaluated. Subsequently, the levels of LL-37 in the culture supernatants of transfected HSEs, as well as the local expression, were determined. It was found that LL-37 treatment significantly promoted the cellular proliferation of HSEs. Furthermore, HSEs that express elevated levels of LL-37 were shown to possess histological characteristics close to the normal skin and display enhanced antimicrobial activity against . These findings demonstrate that HSEs expressing LL-37 through nonviral modification of skin cells are a promising approach for the prevention of bacterial colonization in wounds.
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http://dx.doi.org/10.1089/hum.2021.034DOI Listing
October 2021

Hb Brugg [:c.63C>A]: Report of an Ultra-Rare Variant Hemoglobin and Its Co-inheritance with Hb D-Punjab.

Indian J Hematol Blood Transfus 2021 Apr 10;37(2):326-328. Epub 2020 Aug 10.

Department of Hematology, Level 5, Research Block A, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh, India.

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http://dx.doi.org/10.1007/s12288-020-01331-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012423PMC
April 2021

Congenital erythrocytosis.

Eur J Haematol 2021 Jul 23;107(1):29-37. Epub 2021 Apr 23.

Department of Hematology, Postgraduate Institute of Medical Education & Research, Chandigarh, India.

Erythrocytosis, or increased red cell mass, may be labeled as primary or secondary, depending on whether the molecular defect is intrinsic to the red blood cells/their precursors or extrinsic to them, the latter being typically associated with elevated erythropoietin (EPO) levels. Inherited/congenital erythrocytosis (CE) of both primary and secondary types is increasingly recognized as the cause in many patients in whom acquired, especially neoplastic causes have been excluded. During the past two decades, the underlying molecular mechanisms of CE are increasingly getting unraveled. Gain-in-function mutations in the erythropoietin receptor gene were among the first to be characterized in a disorder termed primary familial and congenital polycythemia. Another set of mutations affect the components of the oxygen-sensing pathway. Under normoxic conditions, the hypoxia-inducible factor (HIF), upon hydroxylation by the prolyl-4-hydroxylase domain protein 2 (PHD2) enzyme, is degraded by the von Hippel-Lindau protein. In hypoxic conditions, failure of prolyl hydroxylation leads to stabilization of HIF and activation of the EPO gene. CE has been found to be caused by loss-of-function mutations in VHL and PHD2/EGLN1 as well as gain-of-function mutations in HIF-2α (EPAS1), all resulting in constitutive activation of EPO signaling. Apart from these, globin gene mutations leading to formation of high oxygen affinity hemoglobins also cause CE. Rarely, bisphosphoglycerate mutate mutations, affecting the 2,3-bisphosphoglycerate levels, can increase the oxygen affinity of hemoglobin and cause CE. This narrative review examines the current mutational spectrum of CE and the distinctive pathogenetic mechanisms that give rise to this increasingly recognized condition in various parts of the world.
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http://dx.doi.org/10.1111/ejh.13632DOI Listing
July 2021

Demographic & clinical profile of patients with COVID-19 at a tertiary care hospital in north India.

Indian J Med Res 2021 Jan & Feb;153(1 & 2):115-125

Department of Internal Medicine, Postgraduate Institute of Medical Education & Research, Chandigarh, India.

Background & Objectives: The COVID-19 pandemic emerged as a major public health emergency affecting the healthcare services all over the world. It is essential to analyze the epidemiological and clinical characteristics of patients with COVID-19 in different parts of our country. This study highlights clinical experience in managing patients with COVID-19 at a tertiary care centre in northern India.

Methods: Clinical characteristics and outcomes of consecutive adults patients admitted to a tertiary care hospital at Chandigarh, India, from April 1 to May 25, 2020 were studied. The diagnosis of SARS-CoV-2 infection was confirmed by real-time reverse transcriptase polymerase chain reaction (RT-PCR) on throat and/or nasopharyngeal swabs. All patients were managed according to the institute's consensus protocol and in accordance with Indian Council of Medical Research guidelines.

Results: During the study period, 114 patients with SARS-CoV-2 infection were admitted. The history of contact with COVID-19-affected individuals was available in 75 (65.8%) patients. The median age of the patients was 33.5 yr (13-79 yr), and there were 66 (58%) males. Of the total enrolled patients, 48 (42%) were symptomatic. The common presenting complaints were fever (37, 77%), cough (26, 54%) and shortness of breath (10, 20.8%). Nineteen (17%) patients had hypoxia (SpO<94%) at presentation and 36 (31%) had tachypnoea (RR >24). Thirty four (29.8%) patients had an accompanying comorbid illness. Age more than 60 yr and presence of diabetes and hypertension were significantly associated with severe COVID-19 disease. Admission to the intensive care unit (ICU) was needed in 18 patients (52%), with three (2.6%) patients requiring assisted ventilation. Mortality of 2.6 per cent (3 patients) was observed.

Interpretation & Conclusions: Majority of the patients with COVID-19 infection presenting to our hospital were young and asymptomatic. Fever was noted only in three-fourth of the patients and respiratory symptoms in half of them. Patients with comorbidities were more vulnerable to complications. Triaged classification of patients and protocol-based treatment resulted in good outcomes and low case fatality.
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http://dx.doi.org/10.4103/ijmr.IJMR_2311_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184067PMC
April 2021

Secondary haemophagocytic lymphohistiocytosis (HLH) triggered by Salmonella typhi.

Postgrad Med J 2021 Mar 31. Epub 2021 Mar 31.

Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.1136/postgradmedj-2021-139999DOI Listing
March 2021

Cartilage lamina splendens inspired nanostructured coating for biomaterial lubrication.

J Colloid Interface Sci 2021 Jul 17;594:435-445. Epub 2021 Mar 17.

University of Groningen and University Medical Center Groningen, Department of Biomedical Engineering, Antonius Deusinglaan 1, 9713 AV Groningen, the Netherlands. Electronic address:

Biomaterials that are used in biological systems, such as polycarbonate urethane (PCU) knee joint implants and contact lenses, generally lack lubrication. This limits their integration with the body and impedes their function. Here, we propose a nanostructured film based on hydrophilic polysaccharide hyaluronic acid conjugated with dopamine (HADN) and zwitterionic reduced glutathione (Glu), which forms a composite coating (HADN-Glu) to enhance the lubrication between cartilage and PCU. HADN was synthesized by carbodiimide chemistry between hyaluronic acid and dopamine and deposited on PCU surface under mild oxidative conditions. Then, zwitterionic peptide-reduced glutathione was bioconjugated to HADN, forming a lubrication film. Analysis based on X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM) and wettability indicated that HADN and Glu had grafted successfully onto the PCU surface. Measurements of the coefficient of friction (COF), friction energy dissipation and cartilage roughness indicated that cartilage was effectively protected by the high lubrication of HADN-Glu. Both at low and high applied loads, this effect was likely due to the enhanced boundary lubrication enabled by HADN-Glu on the PCU surface. Moreover, HADN-Glu is highly biocompatible with chondrocyte cells, suggesting that this film will benefit the design of implants where lubrication is needed.
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http://dx.doi.org/10.1016/j.jcis.2021.03.052DOI Listing
July 2021

The Evolution of Sox Gene Repertoires and Regulation of Segmentation in Arachnids.

Mol Biol Evol 2021 07;38(8):3153-3169

Department of Biological and Medical Sciences, Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, United Kingdom.

The Sox family of transcription factors regulates many processes during metazoan development, including stem cell maintenance and nervous system specification. Characterizing the repertoires and roles of these genes can therefore provide important insights into animal evolution and development. We further characterized the Sox repertoires of several arachnid species with and without an ancestral whole-genome duplication and compared their expression between the spider Parasteatoda tepidariorum and the harvestman Phalangium opilio. We found that most Sox families have been retained as ohnologs after whole-genome duplication and evidence for potential subfunctionalization and/or neofunctionalization events. Our results also suggest that Sox21b-1 likely regulated segmentation ancestrally in arachnids, playing a similar role to the closely related SoxB gene, Dichaete, in insects. We previously showed that Sox21b-1 is required for the simultaneous formation of prosomal segments and sequential addition of opisthosomal segments in P. tepidariorum. We studied the expression and function of Sox21b-1 further in this spider and found that although this gene regulates the generation of both prosomal and opisthosomal segments, it plays different roles in the formation of these tagmata reflecting their contrasting modes of segmentation and deployment of gene regulatory networks with different architectures.
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http://dx.doi.org/10.1093/molbev/msab088DOI Listing
July 2021

2',7'-Dichlorofluorescein (DCF) or 2',7'-dichlorodihydrofluorescein diacetate (DCFH2-DA) to measure reactive oxygen species in erythrocytes.

Biomed Pharmacother 2021 06 18;138:111512. Epub 2021 Mar 18.

Department of Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. Electronic address:

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http://dx.doi.org/10.1016/j.biopha.2021.111512DOI Listing
June 2021

Development of a Need-based Interventional Skin Care Protocol on Incontinence-associated Dermatitis among Critically Ill Patients.

Indian J Crit Care Med 2021 Feb;25(2):158-165

Department of Critical Care Nursing, Himalayan College of Nursing, Swami Rama Himalayan University, Dehradun, Uttarakhand, India.

Background: Incontinence-associated dermatitis (IAD) is a potentially serious skin injury that can lead to pressure ulcers (PUs). Many studies have indicated the need for evidence to find the most effective skin care protocol to reduce the incidence and severity of IAD in critically ill patients.

Aim And Objective: To develop a need-based interventional skin care protocol on IAD after identifying the risk of developing IAD in critically ill patients and by assessing the nurse's knowledge and practice on IAD.

Materials And Methods: Quantitative research approach with an exploratory research design was adopted in the study. A total of 40 staff nurses and 100 patients were included. To assess the knowledge of staff nurses regarding IAD, a knowledge questionnaire was administered and the IAD prevention practice among staff nurses was assessed with the help of an observation checklist. The risk of IAD among 100 critically ill patients was observed by the investigator, using a perineal risk assessment tool. The obtained data were analyzed by using descriptive and inferential statistics. The protocol was developed by the researcher and it was validated by 5 experts.

Results: The results revealed that most of patients (60%) had a high risk for development of IAD. Most of the nurses had poor knowledge (40%) and had poor practice in assessment, perineal area, and prevention of infection area. Hence considering all these aspects, a protocol was developed.

Conclusion: The researchers developed a need-based skin care protocol to decrease the development of IAD.

How To Cite This Article: Sharma P, Latha S, Sharma RK. Development of a Need-based Interventional Skin Care Protocol on Incontinence-associated Dermatitis among Critically Ill Patients. Indian J Crit Care Med 2021;25(2):158-165.
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http://dx.doi.org/10.5005/jp-journals-10071-23716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922448PMC
February 2021

Lubricating properties of chewing stimulated whole saliva from patients suffering from xerostomia.

Clin Oral Investig 2021 Jul 4;25(7):4459-4469. Epub 2021 Mar 4.

Department of Biomedical Engineering, University of Groningen and University Medical Center Groningen, Antonius Deusinglaan 1, 9713AV, Groningen, The Netherlands.

Objectives: The study aimed to quantify the lubricating properties of chewing stimulated whole saliva from healthy controls (n = 22), from patients suffering from primary Sjögren's syndrome (n = 37) and from patients undergoing head-and-neck radiotherapy (n = 34).

Materials And Methods: All participants had to complete the Xerostomia Inventory questionnaire to score dry mouth sensation. Lubrication was measured using an ex vivo tongue-enamel friction system in terms of Relief and Relief period. MUC5b and total protein concentrations of the saliva samples were measured by an enzyme-linked immunosorbent assay and a bicinchoninic acid assay, respectively.

Results: Relief of Sjögren's patients' saliva and post-irradiation patients' saliva was similar compared with healthy controls, but saliva from post-irradiation patients lubricated significantly better than saliva from Sjögren's patients. The Relief period was similar between the three groups. The Relief and Relief period were higher for saliva samples post-irradiation compared to pre-irradiation. MUC5b and total protein concentrations were comparable in all groups. MUC5b and total protein output were significantly lower in patients subjected to radiotherapy compared to saliva from healthy controls and pre-irradiation patients. MUC5b concentrations positively correlated with lubricating properties of post-irradiation patient saliva.

Conclusions: The lubricating properties of patient saliva were not any worse than healthy controls. Lower flow rate leads to lower availability of saliva in the oral cavity and decreases the overall output of protein and MUC5b, which might result in an insufficient replenishing of the mucosal salivary film.

Clinical Relevance: An insufficient replenishing might underlie the sensation of a dry mouth and loss of oral function.
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http://dx.doi.org/10.1007/s00784-020-03758-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310523PMC
July 2021

A conserved role for arrow in posterior axis patterning across Arthropoda.

Dev Biol 2021 07 16;475:91-105. Epub 2021 Feb 16.

Department of Integrative Biology, University of Wisconsin-Madison, Madison, WI, USA 53706. Electronic address:

Segmentation is a key characteristic of Arthropoda that is linked to the evolutionary success of this lineage. It has previously been shown in both vertebrates and short germ insects that posterior segmentation requires canonical Wnt (cWnt) signaling, which maintains the expression of Caudal and the posterior growth zone; disruption of cWnt signaling incurs posterior truncations in these lineages due to the loss of the tail bud. However, comparable datasets for Wnt signaling are limited outside of holometabolous insects, due to incomparable phenotypic spectra and inefficacy of gene misexpression methods in certain model species. We applied RNA interference (RNAi) against the Wnt co-receptor arrow (arr), a key member of the cWnt signaling pathway in holometabolous insects and vertebrates, to examine posterior axis elongation of the cobweb spider Parasteatoda tepidariorum (short germ embryogenesis; one Wnt8 homolog), the cricket Gryllus bimaculatus (intermediate germ; one Wnt8 homolog), and the milkweed bug Oncopeltus fasciatus (short germ; two Wnt8 homologs). Knockdown of arr in insects resulted in posterior truncations affecting the gnathos through the abdomen in O. fasciatus, whereas posterior truncations only affected the T3 segment through the abdomen in G. bimaculatus. Spider embryos with disrupted arr expression exhibited defects along the entire axis, including segmentation defects throughout the germband. RNA-Seq-based differential gene expression analysis of severe Ptep-arr loss-of-function phenotypes at two developmental stages was used to confirm that knockdown of Ptep-arr results in systemic disruption of the Wnt pathway. Intriguingly, we found that knockdown of arr did not abrogate Wnt8 expression in any of the three species, with cad expression additionally retained in severe loss-of-function phenotypes in the cricket and the spider. Together with data from a holometabolous insect, our results suggest that cWnt signaling is not required for maintenance of Wnt8 expression across Arthropoda. These outcomes underscore the diagnostic power of differential gene expression analyses in characterizing catastrophic phenotypes in emerging model species.
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http://dx.doi.org/10.1016/j.ydbio.2021.02.006DOI Listing
July 2021

Low-grade Mucinous Appendiceal Neoplasm: a Tumor in Disguise of Appendicitis.

J Gastrointest Cancer 2021 Sep 11;52(3):1134-1138. Epub 2021 Feb 11.

Department of Surgical Oncology, Bhagwan Mahaveer Cancer Hospital and Research Centre, Jaipur, Rajasthan, India.

Appendiceal mucinous neoplasms are a rare malignancy, but it is an important diagnostic entity. Ultrasonography and CT scan represent useful method for diagnosis; however, diagnosis is often incidental or intraoperative finding at resection for suspicion of appendicitis. Appendiceal mucinous neoplasm is commonly misdiagnosed as acute appendicitis, adnexal mass, or retroperitoneal tumors. Our case represents the importance of developing a high index of suspicion of appendiceal malignancy and mucocele rupture in patients who are planned for appendectomy. There is risk of second malignancy mostly of ovary, breast, kidney, and gastrointestinal tract simultaneously in about 30% of patients of appendiceal mucinous neoplasm. Low-grade mucinous neoplasm has excellent prognosis after standard appendectomy. Advanced stage low-grade mucinous neoplasm involving periappendiceal area or with nodal metastasis is treated by appendectomy with right hemicolectomy and lymph node dissection. We report a case of low-grade appendiceal mucinous neoplasm in a 65-year-old female with past history of surgery for benign bilateral adnexal lesions.
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http://dx.doi.org/10.1007/s12029-021-00593-2DOI Listing
September 2021

Taxonomic Sampling and Rare Genomic Changes Overcome Long-Branch Attraction in the Phylogenetic Placement of Pseudoscorpions.

Mol Biol Evol 2021 05;38(6):2446-2467

Department of Integrative Biology, University of Wisconsin-Madison, Madison, WI, USA.

Long-branch attraction is a systematic artifact that results in erroneous groupings of fast-evolving taxa. The combination of short, deep internodes in tandem with long-branch attraction artifacts has produced empirically intractable parts of the Tree of Life. One such group is the arthropod subphylum Chelicerata, whose backbone phylogeny has remained unstable despite improvements in phylogenetic methods and genome-scale data sets. Pseudoscorpion placement is particularly variable across data sets and analytical frameworks, with this group either clustering with other long-branch orders or with Arachnopulmonata (scorpions and tetrapulmonates). To surmount long-branch attraction, we investigated the effect of taxonomic sampling via sequential deletion of basally branching pseudoscorpion superfamilies, as well as varying gene occupancy thresholds in supermatrices. We show that concatenated supermatrices and coalescent-based summary species tree approaches support a sister group relationship of pseudoscorpions and scorpions, when more of the basally branching taxa are sampled. Matrix completeness had demonstrably less influence on tree topology. As an external arbiter of phylogenetic placement, we leveraged the recent discovery of an ancient genome duplication in the common ancestor of Arachnopulmonata as a litmus test for competing hypotheses of pseudoscorpion relationships. We generated a high-quality developmental transcriptome and the first genome for pseudoscorpions to assess the incidence of arachnopulmonate-specific duplications (e.g., homeobox genes and miRNAs). Our results support the inclusion of pseudoscorpions in Arachnopulmonata (new definition), as the sister group of scorpions. Panscorpiones (new name) is proposed for the clade uniting Scorpiones and Pseudoscorpiones.
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http://dx.doi.org/10.1093/molbev/msab038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136511PMC
May 2021

Chediak-Higashi syndrome: a review of the past, present, and future.

Drug Discov Today Dis Models 2020 9;31:31-36. Epub 2019 Dec 9.

Section of Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.

Since the initial description of Chediak-Higashi syndrome (CHS), over 75 years ago, several studies have been conducted to underscore the role of the lysosomal trafficking regulator gene in the pathogenesis of disease. CHS is a rare autosomal recessive disorder, which is caused by biallelic mutations in the highly conserved gene. The disease is characterized by partial oculocutaneous albinism, prolonged bleeding, immune and neurologic dysfunction, and risk for the development of hemophagocytic lympohistiocytosis (HLH). The presence of giant secretory granules in leukocytes is the classical diagnostic feature, which distinguishes CHS from closely related Griscelli and Hermansky-Pudlak syndromes. While the exact mechanism of the formation of the giant granules in CHS patients is not understood, dysregulation of LYST function in regulating lysosomal biogenesis has been proposed to play a role. In this review, we discuss the clinical characteristics of the disease and highlight the functional consequences of enlarged lysosomes and lysosome-related organelles (LROs) in CHS.
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http://dx.doi.org/10.1016/j.ddmod.2019.10.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793027PMC
December 2019

Evaluation of a flow cytometric test for G6PD-deficient erythrocytes.

Trop Med Int Health 2021 04 2;26(4):462-468. Epub 2021 Feb 2.

Department of Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Objective: Glucose-6-phosphate dehydrogenase (G6PD) deficiency, an X-linked recessive disorder, is the commonest erythrocytic enzymopathy worldwide. Reliable diagnosis and severity prediction in G6PD-deficient/heterozygous females remain challenging. A recently developed flow cytometric test for G6PD deficiency has shown promise in precisely identifying deficient females. This paper presents our experiences with this test in a subtropical setting and presents a modification in flow cytometric data acquisition strategy.

Methods: The methaemoglobin reduction + ferryl Hb generation-based flow cytometric G6PD test was compared with the screening methaemoglobin reduction test (MRT) and confirmatory G6PD enzyme activity assay (EAA) in 20 G6PD-deficient males, 22 G6PD-heterozygous/deficient females and 20 controls. Stained cells were also assessed for bright/dim G6PD activity under a fluorescent microscope.

Results: Flow cytometry separated and quantified %bright cells in heterozygous/deficient females, objectively classifying them into 6 normal (>85% bright cells), 14 intermediate (10-85%) and two G6PD-deficient (<10% bright cells). Concordance with MRT was 89% (55/62 cases) and with EAA was 77% (48/62 cases). Fluorometrically predicted violet laser excitation (405-nm) with signal acquisition in the 425-475 nm region was a technical advancement noted for the first time in this paper.

Conclusion: Flow cytometry/fluorescence microscopy represent technically straightforward methods for the detection and quantification of G6PD-deficient erythrocytes. Based on our results, we recommend their application as a first-line investigation to screen females who are prescribed an oxidant drug like primaquine or dapsone.
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http://dx.doi.org/10.1111/tmi.13547DOI Listing
April 2021

Systemic paralogy and function of retinal determination network homologs in arachnids.

BMC Genomics 2020 Nov 23;21(1):811. Epub 2020 Nov 23.

Department of Integrative Biology, University of Wisconsin-Madison, Madison, WI, 53706, USA.

Background: Arachnids are important components of cave ecosystems and display many examples of troglomorphisms, such as blindness, depigmentation, and elongate appendages. Little is known about how the eyes of arachnids are specified genetically, let alone the mechanisms for eye reduction and loss in troglomorphic arachnids. Additionally, duplication of Retinal Determination Gene Network (RDGN) homologs in spiders has convoluted functional inferences extrapolated from single-copy homologs in pancrustacean models.

Results: We investigated a sister species pair of Israeli cave whip spiders, Charinus ioanniticus and C. israelensis (Arachnopulmonata, Amblypygi), of which one species has reduced eyes. We generated embryonic transcriptomes for both Amblypygi species, and discovered that several RDGN homologs exhibit duplications. We show that duplication of RDGN homologs is systemic across arachnopulmonates (arachnid orders that bear book lungs), rather than being a spider-specific phenomenon. A differential gene expression (DGE) analysis comparing the expression of RDGN genes in field-collected embryos of both species identified candidate RDGN genes involved in the formation and reduction of eyes in whip spiders. To ground bioinformatic inference of expression patterns with functional experiments, we interrogated the function of three candidate RDGN genes identified from DGE using RNAi in the spider Parasteatoda tepidariorum. We provide functional evidence that one of these paralogs, sine oculis/Six1 A (soA), is necessary for the development of all arachnid eye types.

Conclusions: Our work establishes a foundation to investigate the genetics of troglomorphic adaptations in cave arachnids, and links differential gene expression to an arthropod eye phenotype for the first time outside of Pancrustacea. Our results support the conservation of at least one RDGN component across Arthropoda and provide a framework for identifying the role of gene duplications in generating arachnid eye diversity.
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http://dx.doi.org/10.1186/s12864-020-07149-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681978PMC
November 2020
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