Publications by authors named "Muhammad Hassan"

319 Publications

Efficient degradation of Bisphenol A by dielectric barrier discharge non-thermal plasma: Performance, degradation pathways and mechanistic consideration.

Chemosphere 2021 Jul 21;286(Pt 1):131627. Epub 2021 Jul 21.

School of Environmental Science & Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China. Electronic address:

The discharge of recalcitrant and persistent organic pollutants into the environment and subsequent adverse impacts on the ecosystem has aroused a great concern all over the world. In this study, dielectric barrier discharge (DBD) non-thermal plasma was employed to eliminate bisphenol A (BPA). The influences of several vital experimental parameters, including discharge voltage, initial pH of solution, and rate of water flow on degradation of BPA, were explored in detail. In addition, the real wastewater from pharmaceutical factory was utilized to test the oxidation performance of DBD system. 96.8% chemical oxygen demand removal was achieved using DBD system. Radical quenching experiment as well as electron paramagnetic resonance test demonstrated that OH was the main reactive oxygen species for the degradation of BPA. Moreover, eight major BPA degradation intermediates were identified by UPLC-MS. Ultimately, based on the UPLC-MS test results, a possible degradation pathway of BPA was proposed.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131627DOI Listing
July 2021

Monitoring System-Based Flying IoT in Public Health and Sports Using Ant-Enabled Energy-Aware Routing.

J Healthc Eng 2021 1;2021:1686946. Epub 2021 Jul 1.

Department of Information Technology Specialization, FPT University, Hoa Lac High Tech Park, Hanoi, Vietnam.

In recent decades, the Internet of flying networks has made significant progress. Several aerial vehicles communicate with one another to form flying ad hoc networks. Unmanned aerial vehicles perform a wide range of tasks that make life easier for humans. However, due to the high frequency of mobile flying vehicles, network problems such as packet loss, latency, and perhaps disrupted channel links arise, affecting data delivery. The use of UAV-enabled IoT in sports has changed the dynamics of tracking and working on player safety. WBAN can be merged with aerial vehicles to collect data regarding health and transfer it to a base station. Furthermore, the unbalanced energy usage of flying things will result in earlier mission failure and a rapid decline in network lifespan. This study describes the use of each UAV's residual energy level to ensure a high level of safety using an ant-based routing technique called AntHocNet. In health care, the use of IoT-assisted aerial vehicles would increase operational performance, surveillance, and automation optimization to provide a smart application of flying IoT. Apart from that, aerial vehicles can be used in remote communication for treatment, medical equipment distribution, and telementoring. While comparing routing algorithms, simulation findings indicate that the proposed ant-based routing protocol is optimal.
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http://dx.doi.org/10.1155/2021/1686946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270719PMC
July 2021

Cold Stress in Wheat: Plant Acclimation Responses and Management Strategies.

Front Plant Sci 2021 8;12:676884. Epub 2021 Jul 8.

School of Agronomy, Anhui Agricultural University, Hefei, China.

Unpredicted variability in temperature is associated with frequent extreme low-temperature events. Wheat is a leading crop in fulfilling global food requirements. Climate-driven temperature extremes influence the vegetative and reproductive growth of wheat, followed by a decrease in yield. This review describes how low temperature induces a series of modifications in the morphophysiological, biochemical, and molecular makeup of wheat and how it is perceived. To cope with these modifications, crop plants turn on their cold-tolerance mechanisms, characterized by accumulating soluble carbohydrates, signaling molecules, and cold tolerance gene expressions. The review also discusses the integrated management approaches to enhance the performance of wheat plants against cold stress. In this review, we propose strategies for improving the adaptive capacity of wheat besides alleviating risks of cold anticipated with climate change.
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http://dx.doi.org/10.3389/fpls.2021.676884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299469PMC
July 2021

Clinical and biochemical indicators of disease severity and neurological findings in COVID-19: A study of King Edward Medical University (KEMU), Pakistan.

Pak J Pharm Sci 2021 Jan;34(1(Supplementary)):275-281

Department of Neurology, King Edward Medical University (KEMU), Mayo Hospital, Lahore, Pakistan.

This study investigated the significance of difference between presence and absence of different neurological findings in COVID-19, in relation with the biochemistry. Various significant correlations in connection with the disease severity and clinical factors were also identified. 351 COVID-19 patients were included. Different laboratory/ clinical findings were investigated. Correlations Kendall's tau and Pearson Chi-Square were applied to find the correlations between severity and clinical findings. The Mann-Whitney Test was applied for a comparison between two types of neurological groups for each biochemistry parameter. Headache was reported in 28% and dizziness in 13% patients. The impaired smell and impaired taste were reported in 28.5% and 36.2% patients, respectively. The muscle pain was present in 39% patients. 80% patients had low lymphocytes & 70% had high neutrophils. 54.5% were found with high ALP. LDH was elevated in 73%. Severity was found significantly correlated with decreased oxygen saturation, age and raised levels of urea, creatinine and LDH. The groups (with/without CNS involvement) were statistically different in ALP, groups (with/without PNS involvement) in WBC, lymphocytes, neutrophils, ALP, urea, creatinine, CK, CKMB and LDH and groups (with/without MSK involvement) in WBC. Oxygen saturation, age, urea, creatinine and LDH are significant indicators of disease severity in COVID-19. The altered levels of different biochemistry can impact the neurological states of COVID-19 patients.
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January 2021

Effects of silicon on heavy metal uptake at the soil-plant interphase: A review.

Ecotoxicol Environ Saf 2021 Oct 14;222:112510. Epub 2021 Jul 14.

College of Grassland Science and Technology, Sichuan Agricultural University, Chengdu 611130, China. Electronic address:

Silicon (Si) is the second richest element in the soil and surface of earth crust with a variety of positive roles in soils and plants. Different soil factors influence the Si bioavailability in soil-plant system. The Si involves in the mitigation of various biotic (insect pests and pathogenic diseases) and abiotic stresses (salt, drought, heat, and heavy metals etc.) in plants by improving plant tolerance mechanism at various levels. However, Si-mediated restrictions in heavy metals uptake and translocation from soil to plants and within plants require deep understandings. Recently, Si-based improvements in plant defense system, cell damage repair, cell homeostasis, and regulation of metabolism under heavy metal stress are getting more attention. However, limited knowledge is available on the molecular mechanisms by which Si can reduce the toxicity of heavy metals, their uptake and transfer from soil to plant roots. Thus, this review is focused the following facets in greater detail to provide better understandings about the role of Si at molecular level; (i) how Si improves tolerance in plants to variable environmental conditions, (ii) how biological factors affect Si pools in the soil (iii) how soil properties impact the release and capability of Si to decrease the bioavailability of heavy metals in soil and their accumulation in plant roots; (iv) how Si influences the plant root system with respect to heavy metals uptake or sequestration, root Fe/Mn plaque, root cell wall and compartment; (v) how Si makes complexes with heavy metals and restricts their translocation/transfer in root cell and influences the plant hormonal regulation; (vi) the competition of uptake between Si and heavy metals such as arsenic, aluminum, and cadmium due to similar membrane transporters, and (vii) how Si-mediated regulation of gene expression involves in the uptake, transportation and accumulation of heavy metals by plants and their possible detoxification mechanisms. Furthermore, future research work with respect to mitigation of heavy metal toxicity in plants is also discussed.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112510DOI Listing
October 2021

A 24-generation-old founder mutation impairs splicing of RBBP8 in Pakistani families affected with Jawad syndrome.

Clin Genet 2021 Jul 16. Epub 2021 Jul 16.

Cologne Center for Genomics (CCG) and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.

Jawad syndrome is a multiple congenital anomaly and intellectual disability syndrome with mutation in RBBP8 reported only in two families. Here, we report on two new families from Pakistan and identified a previously reported variant in RBBP8, NM_002894.3:c.1808-1809delTA. We could show that this mutation impairs splicing resulting in two different abnormal transcripts. Finally, we could verify a shared haplotype among all four families and estimate the founder event to have occurred some 24 generations ago.
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http://dx.doi.org/10.1111/cge.14028DOI Listing
July 2021

Association of HLA-B Gene Polymorphisms with Type 2 Diabetes in Pashtun Ethnic Population of Khyber Pakhtunkhwa, Pakistan.

J Diabetes Res 2021 16;2021:6669731. Epub 2021 Jun 16.

Department of Pharmacy, University of Peshawar, Pakistan.

Human leukocyte antigen (HLA) system is the most polymorphic and gene dense region of human DNA that has shown many disease associations. It has been further divided into HLA classes I, II, and III. Polymorphism in HLA class II genes has been reported to play an important role in the pathogenesis of type 1 diabetes (T1D). It also showed association with T2D in different ethnic populations. However, a little is known about the relationship of HLA class I gene polymorphism and T2D. This study has evaluated the association of HLA-B (class I gene) variants with T2D in Pashtun ethnic population of Khyber Pakhtunkhwa. In the first phase of the study, whole exome sequencing (WES) of 2 pooled DNA samples was carried out, and DNA pools used were constructed from 100 diabetic cases and 100 control subjects. WES results identified a total of = 17 SNPs in HLA-B gene. In the next phase, first 5 out of = 17 reported SNPs were genotyped using MassARRAY® system in order to validate WES results and to confirm association of selected SNPs with T2D. Minor allele frequencies (MAFs) and selected SNPs×T2D association were determined using chi-square test and logistic regression analysis. The frequency of minor C allele was significantly higher in the T2D group as compared to control group (45.0% vs. 13.0%) ( = 0.006) for rs2308655 in HLA-B gene. No significant difference in MAF distribution between cases and controls was observed for rs1051488, rs1131500, rs1050341, and rs1131285 ( > 0.05). Binary logistic regression analyses showed significant results for SNP rs2308655 (OR = 2.233, CI (95%) = 1.223-4.077, and = 0.009), while no considerable association was observed for the other 4 SNPs. However, when adjusted for these variants, the association of rs2308655 further strengthened significantly (adjusted OR = 7.485, CI (95%) = 2.353-23.812, and = 0.001), except for rs1131500, which has no additive effect. In conclusion, the finding of this study suggests rs2308655 variant in HLA-B gene as risk variant for T2D susceptibility in Pashtun population.
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http://dx.doi.org/10.1155/2021/6669731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254654PMC
June 2021

Drought-tolerant Pseudomonas sp. showed differential expression of stress-responsive genes and induced drought tolerance in Arabidopsis thaliana.

Physiol Plant 2021 Jul 9. Epub 2021 Jul 9.

Department of Agricultural Chemistry and Soil Science, University of Sydney, Sydney, New South Wales, Australia.

The growth and persistence of rhizobacteria in soils are highly impacted by moisture stress. In this study, we report the first transcript analysis of four Pseudomonas strains (PS1, PS2, PS3, and PS4) isolated from the root-soil interface of rice and maize associated with different moisture levels during water deprivation. Filtered Pseudomonas sp. cells incubated at low (RH10%) and high (RH85%) relative humidity showed decreased survival of all Pseudomonas sp. at RH10% when compared with RH85%. RT-PCR showed differential expression of treS (trehalose synthase), rpoS (sigma factor), mucA (alginate regulatory gene), and fliM (flagellar motor switch protein gene) in response to exposure to RH10%. However, molecular fingerprinting and nutrient assimilation profile of Pseudomonas strains demonstrated genetic and physiological variation between the four strains irrespective of water regime and host. In vitro testing of these strains showed ACC deaminase activity and gibberellic acid, abscisic acid, indole acetic acid, and exopolysaccharide production. We determined that 50 μl of 1.2 × 10  CFU ml of these Pseudomonas strains was enough to protect Arabidopsis plants against drought stress in a pot experiment. Inoculated plants increased their root colonization ability and biomass; however, PS2 showed higher survival (95%), relative water content (59%), chlorophyll (30%), glycine betaine (38%), proline (23%), and reduced MDA (43%) in shoots than irrigated control under induced water deprivation. It can be concluded that all Pseudomonas strains were effective in mitigating drought stress, however, PS2 appears to impart more resistance to drought than the other strains by upregulating key defense mechanisms.
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http://dx.doi.org/10.1111/ppl.13497DOI Listing
July 2021

Ecological impact on development of hemipterous bug ( (hemiptera: pyrrhocoridae) and boll rot disease of cotton () grown in the diversified field.

Saudi J Biol Sci 2021 Jul 9;28(7):3957-3964. Epub 2021 Apr 9.

King Khalid University, College of Science, Department of Biology, Abha 61413, Saudi Arabia.

The experiment was conducted at Cotton Research Station, Multan to study the impact of weather factors and Hemipterous bug on development of cotton boll disease in cotton variety bt- 886 for three consecutive years i.e., 2012, 2013 and 2014. The results revealed that the population of Red Cotton Bug (RCB) per plant remain 0.50 and 0.34 during years 2012 and 2013, respectively but increased during 2014 i.e., 3.21 per plant. The number of unopened bolls (UOB) were more during 2012 i.e., 13.43% with yellowish lint (YL) 76.30% and whitish lint (WL) 23.70% at average maximum temperature of 34.73◦C, minimum temperature of 22.83◦C, RH of 77.43% and 11.08 mm rainfall. Similarly during 2013, the number of unopened bolls were less i.e., 0.34 per plant with YL 1.48 and WL 99.53 per plant when average maximum temperature 34.60C, minimum temperature 23.37C, RH 73.01% and 9.95 mm rainfall. During 2014, RCB population per plant was 3.22 with no UOB and YL was 0.00% and WL was 100% when average maximum temperature 23.70C, minimum temperature 23.18◦C, RH 71.67% and 4.55 mm rainfall. So our results concluded that the cotton bolls rot disease was more during 2012 due to abrupt changes in environmental factors. The RCB may be the carrier of boll rot disease pathogen during more rainfall.
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http://dx.doi.org/10.1016/j.sjbs.2021.03.066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241606PMC
July 2021

Preparation and Characterization of a Novel Sulfonated Titanium Oxide Incorporated Chitosan Nanocomposite Membranes for Fuel Cell Application.

Membranes (Basel) 2021 Jun 17;11(6). Epub 2021 Jun 17.

School of Materials, East China University of Science and Technology, Shanghai 200237, China.

In this study, nano-TiO sulfonated with 1,3-propane sultone (STiO) was incorporated into the chitosan (CS) matrix for the preparation of CS/STiO nanocomposite membranes for fuel cell applications. The grafting of sulfonic acid (-SOH) groups was confirmed by Fourier transform infrared spectroscopy, thermogravimetric analysis and energy-dispersive X-ray spectroscopy. The physicochemical properties of these prepared membranes, such as water uptake, swelling ratio, thermal and mechanical stability, ion exchange capacity and proton conductivity, were determined. The proton conducting groups on the surface of nano-TiO can form continuous proton conducting pathways along the CS/STiO interface and thus improve the proton conductivity of CS/STiO nanocomposite membranes. The CS/STiO nanocomposite membrane with 5 wt% of sulfonated TiO showed a proton conductivity (0.035 S·cm) equal to that of commercial Nafion 117 membrane (0.033 S·cm). The thermal and mechanical stability of the nanocomposite membranes were improved because the interfacial interaction between the -SOH group of TiO and the -NH group of CS can restrict the mobility of CS chains to enhance the thermal and mechanical stability of the nanocomposite membranes. These CS/STiO nanocomposite membranes have promising applications in proton exchange membrane fuel cells.
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http://dx.doi.org/10.3390/membranes11060450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246320PMC
June 2021

Race-Related Differences in the Clinical Presentation and Histopathologic Features of Phyllodes Tumor.

Am Surg 2021 Jun 30:31348211029841. Epub 2021 Jun 30.

Department of Surgery, 12278East Carolina University Brody School of Medicine, Greenville, NC, USA.

Background: Phyllodes tumor (PT) is a rare fibroepithelial lesion of the breast with variable malignant potential. Black women have a higher incidence of a related benign tumor, fibroadenoma, but there are limited epidemiological data on PT. The aim of our study was to evaluate race-related differences in the clinicopathologic features and outcomes of PT.

Methods: Our institutional pathology database was queried for breast specimen reports from 01/2009 to 10/2019 to identify patients with a pathologic diagnosis of PT. Chart review and detailed slide review were performed to obtain clinical and histopathologic variables, respectively.

Results: Among twelve patients, two had malignant PT, three had borderline PT, and seven had benign PT. All patients with malignant and borderline PT were black, compared with 29% of those with benign PT. There were no apparent race-related differences in specific histopathologic features among black vs. non-black women with benign PT. Malignant and borderline PT were relatively larger than benign PT, with mean tumor sizes of 9.0 cm (standard deviation [SD] 4.7 cm), 12.2 cm (SD 9.4 cm), and 5.4 cm (SD 5.8 cm), respectively. Two women had a local recurrence, both of whom were black.

Discussion: In this single-institution retrospective study, we observed disproportionate rates of aggressive histopathologic features and disparate outcomes among black women with PT. A multi-institutional PT registry would facilitate improved knowledge about race-related differences in the presentation and outcomes of this rare tumor.
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http://dx.doi.org/10.1177/00031348211029841DOI Listing
June 2021

Taxonomic notes on owlflies from Pakistan (Neuroptera: Myrmeleontidae: Ascalaphinae).

Zootaxa 2021 May 17;4970(3):401452. Epub 2021 May 17.

Department of Entomology, China Agricultural University, Beijing 100193, China.

Taxonomic notes are presented on the former Ascalaphidae (owlflies), now subfamily Ascalaphinae of the family Myrmeleontidae from Pakistan. An updated checklist of new records is provided that accounts for all known 15 genera and 22 species from Pakistan, excluding the species of the tribe Palparini. Geographical distribution maps and an updated identification key to all known genera and species from Pakistan are also given. We synonymized two monotypic genera, Horischema Mészáros Ábrahám, 2003 and Perissoschema Mészáros Ábrahám, 2003 both as junior synonyms of Ogcogaster Westwood, 1847 based on very similar male genitalia and external morphological characters. Moreover, Perissoschema evae Mészáros Ábrahám, 2003 is treated as a junior synonym of Ogcogaster segmentator Westwood, 1847. We recorded three genera for the first time from Pakistan, i.e., Acheron Lefèbvre, 1842, Glyptobasis McLachlan, 1873, and Suphalomitus van der Weele, 1909. To more completely resolve the generic or specific status of those poorly known species from Pakistan, broader sampling throughout the country is needed.
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http://dx.doi.org/10.11646/zootaxa.4970.3.1DOI Listing
May 2021

Exogenous silicon and hydrogen sulfide alleviates the simultaneously occurring drought stress and leaf rust infection in wheat.

Plant Physiol Biochem 2021 Jun 21;166:558-571. Epub 2021 Jun 21.

Department of Botany and Microbiology, College of Science, King Saud University, Saudi Arabia.

Silicon (Si) and hydrogen sulfide (HS) are known to enhance plant defense against multiple stresses. Current study was conducted to investigate the application of Si and HS alone as well as in combination, improved physiological resilience of wheat plants to drought stress (DS) and pathogen-Puccinia triticina (Pt) infection. We aimed to increase the wheat plant growth and to enhance the DS tolerance and Pt resistance with the concurrent applications of HS and Si. In the first experiment, we selected the best growth enhancing concentration of HS (0.3 mM) and Si (6 mM) to further investigate their tolerance and resistance potential in the pot experiment under DS and pathogen infection conditions. The obtained results reveal that DS has further increased the susceptibility of wheat plants to leaf rust pathogen infection while, the sole application of Si and the simultaneous exogenous treatments of HS + Si enhanced the plant growth, decreased disease incidence, and significantly improved tolerance and defense mechanisms of wheat under individual and interactive stress conditions. The exogenous treatment of HS + Si improved the growth criteria, photosynthetic pigments, osmoprotectants, and defense related enzyme activities. The same treatment also reinforced the endogenous HS, Si, ABA and SA contents while decreased the disease incidence and oxidative stress indicators under individual and combined stress conditions. Overall, results from this study presents the influence of combined drought and P. triticina stress in wheat and reveal the beneficial impacts of concurrent exogenous treatment of HS + Si to mitigate the drought and pathogen (P. triticina) induced adverse effects.
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http://dx.doi.org/10.1016/j.plaphy.2021.06.034DOI Listing
June 2021

Structural changes of corneal epithelium in belantamab-associated superficial keratopathy using anterior segment optical coherence tomography.

Am J Ophthalmol Case Rep 2021 Sep 9;23:101133. Epub 2021 Jun 9.

Spencer Center for Vision Research, Byers Eye Institute, Stanford University, Palo Alto, CA, USA.

Purpose: To describe structural changes in corneal epithelium using anterior segment optical coherence tomography (AS-OCT) in two relapsed and refractory multiple myeloma (RRMM) patients with bilateral belantamab-associated superficial keratopathy (BASK).

Observations Case 1: A 56-year-old male who was diagnosed with RRMM and initiated on belantamab mafodotin, presented on day 42 (three weeks after the second infusion) with decreased pinhole visual acuity from 20/20 and 20/25 to 20/70 and 20/50 in the right eye and left eye, respectively. Slit-lamp examination revealed moderate superficial keratopathy with microcystic-like epithelial changes (MECs) in the paracentral cornea in both eyes. AS-OCT demonstrated increased bilateral heterogeneous signal intensity and hyperreflective lesions as well as increased thickness in the paracentral corneal epithelium with uninvolved central cornea. Given bilateral MECs, the third infusion was withheld, and then given on day 62 after five weeks of drug-free interval. Although MECs had improved on day 82, pinhole visual acuity remained at 20/50 and 20/40 in the right eye and the left eye. AS-OCT showed that hyperreflective lesions mostly resolved and corneal epithelial thickness returned to baseline, despite a slightly increased persisting heterogeneous signal intensity in the peripheral corneal epithelium in both eyes.

Case 2: A 77-year-old male with RRMM was started on belantamab mafodotin infusions. His pinhole visual acuity decreased from 20/40 and 20/30 at baseline to 20/60 and 20/40 on day 41 (three weeks after the second infusion) in the right eye and left eye, respectively. Slit-lamp examination showed diffuse, moderate MECs in both eyes, which was more severe in the peripheral cornea. AS-OCT demonstrated increased bilateral heterogeneous signal intensity and hyperreflective lesions in the corneal epithelium, which are more severe in the right eye along with increased corneal epithelial thickness. Therefore, belantamab mafodotin was withheld.

Conclusions And Impotance: AS-OCT objectively demonstrated structural changes such as signal intensity and thickness alterations with hyperreflective lesions in the corneal epithelium related to BASK. AS-OCT might be useful for clinicians to monitor ocular surface adverse events in RRMM patients receiving belantamab mafodotin and to adjust therapeutic plans for the patients.
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http://dx.doi.org/10.1016/j.ajoc.2021.101133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208963PMC
September 2021

The Cox model of predicting mortality among melioidosis patients in Northern Malaysia: A retrospective study.

Medicine (Baltimore) 2021 Jun;100(25):e26160

Clinical Research Center, Hospital Sultanah Bahiyah, Ministry of Health Malaysia, Alor Setar, Kedah, Malaysia.

Abstract: Melioidosis is an infectious disease that is initiated by a bacteria recognized as Burkholderia pseudomallei. Despite the high fatality rate from melioidosis, there is a minimal published study about the disease in Malaysia.This study aimed to identify the prognostic factors of mortality among melioidosis patients in northern Malaysia.All inpatient patients who were admitted to Hospital Sultanah Bahiyah, Kedah and Hospital Tuanku Fauziah, Perlis with culture-confirmed melioidosis during the period 2014 to 2017 were included in the study. The study retrospectively collected 510 melioidosis patients from the Melioidosis Registry. Hazard ratio (HR) used in advanced multiple Cox regression was used to obtain the final model of prognostic factors of melioidosis. The analysis was performed using STATA/SE 14.0 for Windows software.From the results, among the admitted patients, 50.1% died at the hospital. The mean age for those who died was 55 years old, and they were mostly male. The most common underlying disease was diabetes mellitus (69.8%), followed by hypertension (32.7%). The majority of cases (86.8%) were bacteremic. The final Cox model identified 5 prognostic factors of mortality among melioidosis patients. The factors were diabetes mellitus, type of melioidosis, platelet count, white blood cell count, and urea value. The results showed that bacteremic melioidosis increased the risk of dying by 3.47 (HR: 3.47, 95% confidence intervals [CI]: 1.67-7.23, P = .001) compared to non-bacteremic melioidosis. Based on the blood investigations, the adjusted HRs from the final model showed that all 3 blood investigations were included as the prognostic factors for the disease (low platelet: HR = 1.76, 95% CI: 1.22-2.54, P = .003; high white blood cell: HR = 1.49, 95% CI 1.06-2.11, P = .023; high urea: HR = 2.92, 95% CI: 1.76-4.85, P < .001; and low level of urea: HR = 2.69, 95% CI: 1.69-4.29, P < .001). By contrast, melioidosis patients with diabetic had 30.0% lower risk of dying from melioidosis compared to those with non-diabetic (HR = 0.70, 95% CI: 0.52-0.94, P = .016).Identifying the prognostic factors of mortality in patients with melioidosis allows a guideline of early management in these patients, which may improve patient's survival.
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http://dx.doi.org/10.1097/MD.0000000000026160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238369PMC
June 2021

Completeness of reporting of quality improvement studies in neonatology is inadequate: a systematic literature survey.

BMJ Open Qual 2021 06;10(2)

Department of Health Research Methods Evidence and Impact, McMaster University, Hamilton, Ontario, Canada

Introduction: Quality improvement (QI) is a growing field of inquiry in healthcare, but the reporting quality of QI studies in neonatology remains unclear. We conducted a systematic survey of the literature to assess the reporting quality of QI studies and factors associated with reporting quality.

Methods: We searched Medline for publications of QI studies from 2016 to 16 April 2020. Pairs of reviewers independently screened citations and assessed reporting quality using a 31-item modified Standards for Quality Improvement Reporting Excellence, 2nd edition (SQUIRE 2.0) checklist. We reported the number (percentage) of studies that reported each item and their corresponding 95% CIs. We used Poisson regression to explore factors associated with reporting quality, namely, journal endorsement of SQUIRE 2.0, declaration of funding sources, year of publication and number of authors. The results were reported as incidence rate ratio (IRR) and 95% CI.

Results: Of 1921 citations, 336 were eligible; among them, we randomly selected 100 articles to assess reporting quality. The mean (standard deviation) number of SQUIRE 2.0 items adhered to was 22.0 (4.5). Percentage of articles reporting each item varied from 26% to 100%. Journal endorsement of SQUIRE 2.0 (IRR=1.11, 95% CI 1.02 to 1.21, p=0.015), declaration of funding sources and increasing number of authors were significantly associated with better reporting.

Conclusions: Reporting quality of QI studies in neonatology is inadequate. Endorsing the SQUIRE 2.0 guideline is a step that journals can implement to enhance the completeness of reporting.
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http://dx.doi.org/10.1136/bmjoq-2020-001273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204179PMC
June 2021

Development of HDAC Inhibitors Exhibiting Therapeutic Potential in T-Cell Prolymphocytic Leukemia.

J Med Chem 2021 Jun 8;64(12):8486-8509. Epub 2021 Jun 8.

Department of Chemical and Physical Sciences, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, Ontario L5L 1C6, Canada.

Epigenetic targeting has emerged as an efficacious therapy for hematological cancers. The rare and incurable T-cell prolymphocytic leukemia (T-PLL) is known for its aggressive clinical course. Current epigenetic agents such as histone deacetylase (HDAC) inhibitors are increasingly used for targeted therapy. Through a structure-activity relationship (SAR) study, we developed an HDAC6 inhibitor KT-531, which exhibited higher potency in T-PLL compared to other hematological cancers. KT-531 displayed strong HDAC6 inhibitory potency and selectivity, on-target biological activity, and a safe therapeutic window in nontransformed cell lines. In primary T-PLL patient cells, where was found to be overexpressed, KT-531 exhibited strong biological responses, and safety in healthy donor samples. Notably, combination studies in T-PLL patient samples demonstrated KT-531 synergizes with approved cancer drugs, bendamustine, idasanutlin, and venetoclax. Our work suggests HDAC inhibition in T-PLL could afford sufficient therapeutic windows to achieve durable remission either as stand-alone or in combination with targeted drugs.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237267PMC
June 2021

SARS-CoV-2 infection with pneumonia and stroke.

Brain Hemorrhages 2021 Jun 2;2(2):88-90. Epub 2021 Feb 2.

Shaheed Zulfiqar Ali Bhutto Medical University (SZABMU), Islamabad, Pakistan.

Background: Covid-19 pandemic has been manifested mainly as respiratory and constitutional symptoms. Though, it may demonstrate the involvement of other systems i.e. cardiovascular system (CVS), central nervous system (CNS) or gastrointestinal system (GI).

Discussion: Systemic manifestation of Covid-19 requires further research. Recent surveys revealed a few alarming facts about Covid-19, that, when it hits the brain, can cause some serious complications like; psychosis, stroke and dementia.

Case Presentation: Here, the case is about two patients, having PCR confirmed Covid-19 and radiographic evidence of stroke, who eventually died during hospital stay. Data collection was done after informed consent and in retrospective manner.
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http://dx.doi.org/10.1016/j.hest.2020.12.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167422PMC
June 2021

Clinical Variants, Characteristics, and Outcomes Among COVID-19 Patients: A Case Series Analysis at a Tertiary Care Hospital in Karachi, Pakistan.

Cureus 2021 Apr 29;13(4):e14761. Epub 2021 Apr 29.

Internal Medicine, OMI Institute, Karachi, PAK.

Introduction Coronavirus disease 2019 (COVID-19) has become a global threat to public health. The current study investigates alterations in the biological estimates concerning the severity, recovery, mortality, and assessment of treatment-based outcomes. Methods A case series of 165 COVID-19 patients admitted to OMI Institute (a tertiary care hospital) was conducted between May and August 2020. The data regarding demographic characteristics, comorbid conditions, radiographic abnormalities, biological estimations, symptoms, treatment, disease progression, complications, and outcomes were recorded using a structured questionnaire. Laboratory estimations included complete blood count (CBC), renal and electrolyte profile, liver function tests (LFTs), hematological indices, and inflammatory markers. Chest X-ray, electrocardiogram (ECG), and a high-resolution computed tomography (HRCT) scan were also performed, and data were extracted from the medical records. Analysis was done using the Statistical Package for the Social Sciences (SPSS) version 22.0. Results Out of the 165 COVID-19 patients, 79.4% recovered and were successfully discharged, while 20.6% of inpatient died. The patients' mean age was 56.03 ± 15.96 years, with a male majority (55.1%). The most common comorbid conditions were diabetes and hypertension; fever and dry cough were among the most frequently reported symptoms. The chest imaging findings among the severe/critical COVID-19 patients showed extensive bilateral patchy opacities. The median laboratory investigations, including neutrophil-to-lymphocyte ratio (NLR) (14.83), C-reactive protein (CRP) (7.4 mg/dl), lactate dehydrogenase (LDH) (786 IU/L), ferritin (1401.15 mcg/ml), and mean oxygen saturation (88.25%), were significantly altered among cases with increased disease severity and those who expired (p<0.05). The proportion of acute respiratory distress syndrome (ARDS) and sepsis development was significantly high among severe/critical COVID-19 patients (p<0.05). Treatment with tocilizumab, remdesivir, doxycycline, ivermectin, enoxaparin sodium, and steroids was deemed to be potentially effective treatment options in terms of reducing COVID-19 severity and chances of recovery. Furthermore, age (OR 1.05; p=0.047), presence of comorbidity (OR 8.471; p=0.004), high NLR, LDH (final outcome) (OR 1.361 and 1.018; p<0.05), and CRP levels (midpoint) (OR 1.631; p=0.05) were identified as the strong predictors of death among COVID-19 patients. Conclusion The study identified several alterations in the clinical profile of the COVID-19 patients concerning severity during the hospital stay, affecting prognosis. Clinically, tocilizumab, remdesivir, doxycycline, ivermectin, enoxaparin sodium, and steroids were identified as potential therapeutic options for COVID-19 due to their ability to alter disease-associated severity and recovery rate.
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http://dx.doi.org/10.7759/cureus.14761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164449PMC
April 2021

Altered Neurotransmitter Expression in the Corticothalamocortical Network of an Absence Epilepsy Model with impaired Feedforward Inhibition.

Neuroscience 2021 07 25;467:73-80. Epub 2021 May 25.

Department of Anatomy, Brain Health Research Centre, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand. Electronic address:

The episodes of brief unconsciousness in patients with childhood absence epilepsy are a result of corticothalamocortical circuitry dysfunction. This dysfunction may arise from multifactorial mechanisms in patients from different genetic backgrounds. In previous studies using the epileptic stargazer mutant mouse, which experience frequent absence seizures, we reported a deficit in AMPAR-mediated feed-forward inhibition of parvalbumin-containing (PV) interneurons. Currently, in order to determine the downstream effects of this impairment on neurotransmitter expression, we performed HPLC of tissue lysates and post-embedding electron microscopy from the cortical and thalamic regions. We report region-specific alterations in GABA expression, but not of glutamate, and most prominently at PV synaptic terminals. These results suggest that impaired feed forward inhibition may occur via reduced activation of these interneurons and concomitant decreased GABAergic signaling. Further investigations into GABAergic control of corticothalamocortical network activity could be key in our understanding of absence seizure pathogenesis.
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http://dx.doi.org/10.1016/j.neuroscience.2021.05.024DOI Listing
July 2021

Combined application of zinc oxide nanoparticles and biofertilizer to induce salt resistance in safflower by regulating ion homeostasis and antioxidant defence responses.

Ecotoxicol Environ Saf 2021 May 5;218:112262. Epub 2021 May 5.

Department of Botany, S.P. College, Srinagar, Jammu and Kashmir, India. Electronic address:

Salinity is a key devastating abiotic factor that hinders the development and yield of safflower. The sole and combined application of zinc oxide nanoparticles (ZnO-NPs) and a biofertilizer (BF) to improve salt tolerance in safflower has not been thoroughly explored. The response of safflower plants in a pot experiment to the foliar spray of ZnO-NPs alone and in combination with a BF was thus detected. We determined that a ZnO-NP concentration of 17 mg/L was sufficient to protect safflower against salinity (250 mM NaCl) by increasing the plant productivity, percent water content, and osmolyte levels. Coapplication of ZnO-NPs and Phytoguard protected safflower plants from salinity stress by improving the activities of antioxidant enzymes and decreasing the levels of proline (leaves (61%) and roots (63%)) and malondialdehyde (MDA) (leaves (54%) and roots (65%)). Under salt stress, the Na content increased, while seed coating with biofertilizer and ZnO-NP spray significantly decreased the Na concentration (74% in leaves and 60% in roots). For the K concentration, however, antagonistic outcomes were observed. Additionally, the combined treatment significantly enhanced agronomic parameters such as the number of leaves and pods per plant, capitulum weight, and the number of yellow and wilted leaves per plant under salinity stress. Thus, ZnO-NPs could be an effective bio-source for the protection of safflower plants under salinity stress. Our findings showed that in the combined treatment of ZnO-NPs and biofertilizer, the salinity tolerance was more pronounced than in the single treatment and untreated control. A thorough analysis at the molecular level, however, is still required to understand the mechanism by which ZnO-NPs and BF in safflower plants alleviate salt stress.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112262DOI Listing
May 2021

Efficacy and safety of ravidasvir plus sofosbuvir in patients with chronic hepatitis C infection without cirrhosis or with compensated cirrhosis (STORM-C-1): interim analysis of a two-stage, open-label, multicentre, single arm, phase 2/3 trial.

Lancet Gastroenterol Hepatol 2021 06 16;6(6):448-458. Epub 2021 Apr 16.

Ministry of Health, Kuala Lumpur, Malaysia.

Background: In low-income and middle-income countries, affordable direct-acting antivirals are urgently needed to treat hepatitis C virus (HCV) infection. The combination of ravidasvir, a pangenotypic non-structural protein 5A (NS5A) inhibitor, and sofosbuvir has shown efficacy and safety in patients with chronic HCV genotype 4 infection. STORM-C-1 trial aimed to assess the efficacy and safety of ravidasvir plus sofosbuvir in a diverse population of adults chronically infected with HCV.

Methods: STORM-C-1 is a two-stage, open-label, phase 2/3 single-arm clinical trial in six public academic and non-academic centres in Malaysia and four public academic and non-academic centres in Thailand. Patients with HCV with compensated cirrhosis (Metavir F4 and Child-Turcotte-Pugh class A) or without cirrhosis (Metavir F0-3) aged 18-69 years were eligible to participate, regardless of HCV genotype, HIV infection status, previous interferon-based HCV treatment, or source of HCV infection. Once daily ravidasvir (200 mg) and sofosbuvir (400 mg) were prescribed for 12 weeks for patients without cirrhosis and for 24 weeks for those with cirrhosis. The primary endpoint was sustained virological response at 12 weeks after treatment (SVR12; defined as HCV RNA <12 IU/mL in Thailand and HCV RNA <15 IU/mL in Malaysia at 12 weeks after the end of treatment). This trial is registered with ClinicalTrials.gov, number NCT02961426, and the National Medical Research Register of Malaysia, NMRR-16-747-29183.

Findings: Between Sept 14, 2016, and June 5, 2017, 301 patients were enrolled in stage one of STORM-C-1. 98 (33%) patients had genotype 1a infection, 27 (9%) had genotype 1b infection, two (1%) had genotype 2 infection, 158 (52%) had genotype 3 infection, and 16 (5%) had genotype 6 infection. 81 (27%) patients had compensated cirrhosis, 90 (30%) had HIV co-infection, and 99 (33%) had received previous interferon-based treatment. The most common treatment-emergent adverse events were pyrexia (35 [12%]), cough (26 [9%]), upper respiratory tract infection (23 [8%]), and headache (20 [7%]). There were no deaths or treatment discontinuations due to serious adverse events related to study drugs. Of the 300 patients included in the full analysis set, 291 (97%; 95% CI 94-99) had SVR12. Of note, SVR12 was reported in 78 (96%) of 81 patients with cirrhosis and 153 (97%) of 158 patients with genotype 3 infection, including 51 (96%) of 53 patients with cirrhosis. There was no difference in SVR12 rates by HIV co-infection or previous interferon treatment.

Interpretation: In this first stage, ravidasvir plus sofosbuvir was effective and well tolerated in this diverse adult population of patients with chronic HCV infection. Ravidasvir plus sofosbuvir has the potential to provide an additional affordable, simple, and efficacious public health tool for large-scale implementation to eliminate HCV as a cause of morbidity and mortality.

Funding: National Science and Technology Development Agency, Thailand; Department of Disease Control, Ministry of Public Health, Thailand; Ministry of Health, Malaysia; UK Aid; Médecins Sans Frontières (MSF); MSF Transformational Investment Capacity; FIND; Pharmaniaga; Starr International Foundation; Foundation for Art, Research, Partnership and Education; and the Swiss Agency for Development and Cooperation.
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http://dx.doi.org/10.1016/S2468-1253(21)00031-5DOI Listing
June 2021

Sodium nitroprusside application improves morphological and physiological attributes of soybean (Glycine max L.) under salinity stress.

PLoS One 2021 16;16(4):e0248207. Epub 2021 Apr 16.

Biology Department, College of Sciences, Imam Mohammad Ibn Saud Islamic University, Riyadh, Kingdom of Saudi Arabia.

Salinity is among the major abiotic stresses negatively affecting the growth and productivity of crop plants. Sodium nitroprusside (SNP) -an external nitric oxide (NO) donor- has been found effective to impart salinity tolerance to plants. Soybean (Glycine max L.) is widely cultivated around the world; however, salinity stress hampers its growth and productivity. Therefore, the current study evaluated the role of SNP in improving morphological, physiological and biochemical attributes of soybean under salinity stress. Data relating to biomass, chlorophyll and malondialdehyde (MDA) contents, activities of various antioxidant enzymes, ion content and ultrastructural analysis were collected. The SNP application ameliorated the negative effects of salinity stress to significant extent by regulating antioxidant mechanism. Root and shoot length, fresh and dry weight, chlorophyll contents, activities of various antioxidant enzymes, i.e., catalase (CAT), superoxide dismutase (SOD), peroxidase (POD) and ascorbate peroxidase (APX) were improved with SNP application under salinity stress compared to control treatment. Similarly, plants treated with SNP observed less damage to cell organelles of roots and leaves under salinity stress. The results revealed pivotal functions of SNP in salinity tolerance of soybean, including cell wall repair, sequestration of sodium ion in the vacuole and maintenance of normal chloroplasts with no swelling of thylakoids. Minor distortions of cell membrane and large number of starch grains indicates an increase in the photosynthetic activity. Therefore, SNP can be used as a regulator to improve the salinity tolerance of soybean in salt affected soils.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248207PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051766PMC
April 2021

Current concepts in the diagnosis and management of antiphospholipid syndrome and ocular manifestations.

J Ophthalmic Inflamm Infect 2021 Apr 9;11(1):11. Epub 2021 Apr 9.

Spencer Center for Vision Research, Byers Eye Institute, Stanford University, 2370 Watson Court, Suite 200, Palo Alto, CA, 94303, USA.

Antiphospholipid syndrome (APS) is an autoimmune disorder associated with obstetrical complications, thrombotic complications involving both arteries and veins, and non-thrombotic manifestations affecting multiple other systems presenting in various clinical forms. Diagnosis requires the presence of antiphospholipid antibodies. The exact pathogenesis of APS is not fully known. However, it has recently been shown that activation of different types of cells by antiphospholipid antibodies plays an important role in thrombosis formation. Ocular involvement is one of the important clinical manifestations of APS and can vary in presentations. Therefore, as an ophthalmologist, it is crucial to be familiar with the ocular findings of APS to prevent further complications that can develop. Furthermore, the ongoing identification of new and specific factors contributing to the pathogenesis of APS may provide new therapeutic options in the management of the disease in the future.
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http://dx.doi.org/10.1186/s12348-021-00240-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032459PMC
April 2021

Assessment and prediction of restless leg syndrome (RLS) in patients with diabetes mellitus type II through artificial intelligence (AI).

Pak J Pharm Sci 2020 Sep;33(5(Special)):2399-2403

Department of Medicine, King Edward Medical University (KEMU), Mayo Hospital Lahore Pakistan.

This study aimed to diagnose the incidence of restless leg syndrome (RLS) in patients with diabetes mellitus (DM) type-2, thorough artificial intelligence based multilayer perceptron (MLP). 300 cases of diabetes mellitus type-2, of age between 18-80 years were included. Point-biserial correlation/Pearson Chi-Square correlations were conducted between RLS and risk factors. We trained a backpropagation MLP via. supervised learning algorithm to predict clinical outcome for RLS. Majority of the patients were having hypertension (63%) and with peripheral neuropathy (69%). Two mostly reported scaled parameters were: 18% 'tiredness' and 14%, 'impact on mood'. A significant correlation was found in RLS with smoking, hypertension and chronic renal failure (CRF). MLP model achieved more than 95% accuracy in predicting the outcome with cross entropy error 0.5%. Following scaled symptomatic variables: 'need/urge to move' (100%) achieved the highest normalized importance, followed by 'relief by moving' (85.7%), 'sleep disturbance' (62%) and 'impact on mood' (51.3%). Artificial intelligence based models can help physicians to identify the pre diagnose RLS, so that active measures can be taken in time to avoid further complications.
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September 2020

Novel Coronavirus-2019 (2019-nCoV): Perspectives of emergence, prophylaxis and predicted treatment approaches.

Pak J Pharm Sci 2020 Sep;33(5):2199-2207

Sindh Institute of Urology and Transplantation (SIUT), Karachi, Pakistan.

Emergence of novel coronavirus-2019 has become an international health concern. The objective of this review is to focus on 2019-nCoV emergence, prophylaxis and to predict the treatment approaches. The first case of 2019-nCoV was noted in Wuhan, China. The WHO has announced this epidemic as pandemic. The 2019-nCoV has +ve ssRNA (29903bp), lipid-bilayer envelope spiked with glycoprotein and bears genome sequences similar to bat coronavirus RaTG13. Antiviral agents like Interferon, Darunavir, Ribavirin, Lopinavir, Remdesivir, Chloroquine and Camostat mesylate may be considered for clinical trials. Chinese herbals may be effective against 2019-nCoV. These include Saikosaponins (triterpene glycosides), Amentoflavone, Scutellarein, Myricetin, extracts of Isatis indigotica, and Houttuynia cordata. Another treatment approach is to administer plasma from COVID-19 recovered patients. RNA vaccines, recombinant vector based vaccine and ACE-2 receptor like molecules may be employed for immunization against COVID-19. Moreover, immunity can be boosted against 2019-nCoV by regular exercise. We have checked Thymoquinone as ligand for various targets of 2019-nCoV (receptor binding domain of spike, RNA polymerase, protease, Nsp9 RNA binding protein, nucleocapsid phosphoprotein, endoribonuclease) by protein-ligand docking server SwissDoc. Thymoquinone can bind effectively to the targets of 2019-nCoV. Hence, it may be an effective candidate for the treatment of COVID-19.
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September 2020

Development and Comparative Analysis of Electrochemically Etched Tungsten Tips for Quartz Tuning Fork Sensor.

Micromachines (Basel) 2021 Mar 8;12(3). Epub 2021 Mar 8.

Department of Mechanical Engineering, Bahauddin Zakariya University, Multan 60011, Pakistan.

Quartz Tuning Fork (QTF) based sensors are used for Scanning Probe Microscopes (SPM), in particular for near-field scanning optical microscopy. Highly sharp Tungsten (W) tips with larger cone angles and less tip diameter are critical for SPM instead of platinum and iridium (Pt/Ir) tips due to their high-quality factor, conductivity, mechanical stability, durability and production at low cost. Tungsten is chosen for its ease of electrochemical etching, yielding high-aspect ratio, sharp tips with tens of nanometer end diameters, while using simple etching circuits and basic electrolyte chemistry. Moreover, the resolution of the SPM images is observed to be associated with the cone angle of the SPM tip, therefore Atomic-Resolution Imaging is obtained with greater cone angles. Here, the goal is to chemically etch W to the smallest possible tip apex diameters. Tips with greater cone angles are produced by the custom etching procedures, which have proved superior in producing high quality tips. Though various methods are developed for the electrochemical etching of W wire, with a range of applications from scanning tunneling microscopy (SPM) to electron sources of scanning electron microscopes, but the basic chemical etching methods need to be optimized for reproducibility, controlling cone angle and tip sharpness that causes problems for the end users. In this research work, comprehensive experiments are carried out for the production of tips from 0.4 mm tungsten wire by three different electrochemical etching techniques, that is, Alternating Current (AC) etching, Meniscus etching and Direct Current (DC) etching. Consequently, sharp and high cone angle tips are obtained with required properties where the results of the W etching are analyzed, with optical microscope, and then with field emission scanning electron microscopy (FE-SEM). Similarly, effects of varying applied voltages and concentration of NaOH solution with comparison among the produced tips are investigated by measuring their cone angle and tip diameter. Moreover, oxidation and impurities, that is, removal of contamination and etching parameters are also studied in this research work. A method has been tested to minimize the oxidation on the surface and the tips were characterized with scanning electron microscope (SEM).
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http://dx.doi.org/10.3390/mi12030286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001380PMC
March 2021

Differences in the characteristics of subjects achieving complete, partial, or no resolution of macular edema in the READ-3 study.

Graefes Arch Clin Exp Ophthalmol 2021 Apr 1. Epub 2021 Apr 1.

Byers Eye Institute, Stanford University, 2370 Watson Court - Suite 200, Palo Alto, CA, 94303, USA.

Purpose: To identify baseline characteristics of subjects enrolled in the READ-3 study that would predict the response of macular edema to ranibizumab (RBZ) therapy at year 1.

Methods: In this post hoc analysis of the READ-3 randomized, multicenter phase 2 clinical trial, subjects with diabetic macular edema (DME) were randomized to receive monthly intravitreal injections of RBZ (0.5 or 2.0 mg) for 6 consecutive injections followed by as-needed treatments based on pre-defined retreatment criteria. In this sub-study, subjects were divided into three groups (persistent, rebound, and resolved) based on edema status at month 12 (M12). Multi-logistic regression was utilized to assess the probability of edema outcomes M12, based on the baseline characteristics.

Results: One hundred twenty-three out of 152 subjects were analyzed for this sub-study. A significant difference was observed in the baseline (BL) central subfield thickness (CST) among the study groups (p < 0.05). BL CST was a significant predictor for edema outcome at M12 with > 80% probability of the subject having persistent edema if BL CST was > 570 μm (p < 0.05). This association persisted when controlled for the dose of RBZ (relative risk (RR), 1.007; p < 0.05). BL CST was also a significant predictor for having persistent edema at M12 in subjects without vitreomacular adhesion (VMA) (> 80% probability of edema persistence at CST > 570 μm [RR, 1.006; p < 0.05]). However, in the presence of VMA, BL CST was no longer a significant predictor of having persistent edema at month 12 (RR, 1.005; p > 0.05).

Conclusions: Subjects with high CST (> 570 μm) at baseline may not benefit from repeated intravitreal injections of anti-VEGF for resolution of edema.
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http://dx.doi.org/10.1007/s00417-021-05148-6DOI Listing
April 2021

Risk Assessment of Flonicamid Resistance in Musca domestica (Diptera: Muscidae): Resistance Monitoring, Inheritance, and Cross-Resistance Potential.

J Med Entomol 2021 Jul;58(4):1779-1787

Pesticides and Environmental Toxicology Laboratory, Department of Plant Protection, College of Food and Agriculture Sciences, King Saud University, Riyadh, Saudi Arabia.

Flonicamid is a chordotonal modulator and novel systemic insecticide that has been used frequently for controlling a broad range of insect pests. The risk of flonicamid resistance was assessed through laboratory selection and determining inheritance pattern and cross-resistance potential to five insecticides in house fly, Musca domestica L. Very low to high flonicamid resistance in M. domestica populations was found compared with the susceptible strain (SS). A flonicamid-selected (Flonica-RS) M. domestica strain developed 57.73-fold resistance to flonicamid screened for 20 generations compared with the SS. Overlapping 95% fiducial limits of LC50 of the F1 and F1ǂ, and dominance values (0.87 for F1 and 0.92 for F1ǂ) revealed an autosomal and incomplete dominant flonicamid resistance. The monogenic model of resistance inheritance suggested a polygenic flonicamid resistance. The Flonica-RS strain displayed negative cross-resistance between flonicamid and sulfoxaflor (0.10-fold) or clothianidin (0.50-fold), and very low cross-resistance between flonicamid and flubendiamide (4.71-fold), spinetoram (4.68-fold), or thiamethoxam (2.02-fold) in comparison with the field population. The estimated realized heritability (h2) value of flonicamid resistance was 0.02. With selection mortality 40-90%, the generations required for a 10-fold increase in LC50 of flonicamid were 94-258 at h2 (0.02) and slope (3.29). Flonicamid resistance was inherited as autosomal, incomplete dominant, and polygenic in the Flonica-RS. Negative or very low cross-resistance between flonicamid and sulfoxaflor, clothianidin, flubendiamide, spinetoram, and thiamethoxam means that these insecticides can be used as alternatives for controlling M. domestica. These data can be useful in devising the management for M. domestica.
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http://dx.doi.org/10.1093/jme/tjab036DOI Listing
July 2021

Bilateral preretinal hemorrhage associated with Kikuchi-Fujimoto disease.

Am J Ophthalmol Case Rep 2021 Jun 2;22:101041. Epub 2021 Mar 2.

Retina Institute of The Carolina and Macular Degeneration Center, Charlotte, NC, USA.

Purpose: To present a case of a patient with human immunodeficiency virus (HIV) disease and Kikuchi-Fujimoto disease (KFD) who presented with a unique pattern of retinopathy.

Observations: A 7-year-old Taiwanese girl with HIV disease who was recently diagnosed with KFD had a sudden onset of blurry vision in both eyes one month after her KFD systemic symptoms had relatively resolved. Ophthalmic examination showed decreased visual acuity in both eyes (OU). On fundus examination, she had bilateral preretinal, subhyaloid, and vitreous hemorrhage that was more severe than anemic retinopathy.

Conclusion: Ocular manifestations in Kikuchi-Fujimoto disease are rare; however, if they occur, presentations may vary. The exact etiology of the disease has remained elusive and controversial. This case is the first report of a patient with HIV disease and KFD presenting with ocular involvement. Furthermore, bilateral preretinal, subhyaloid, and vitreous hemorrhage, which was beyond anemic retinopathy, is an unprecedented manifestation of KFD that has not been previously reported. This case highlights the necessity for clinicians to consider all possible differential diagnoses when evaluating patients with similar findings to identify the best therapeutic approach and avoid unnecessary treatment.
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http://dx.doi.org/10.1016/j.ajoc.2021.101041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940994PMC
June 2021
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