In-silico analysis of interacting pathways through KIM-1 protein interaction in diabetic nephropathy.

BACKGROUND: Human Kidney Injury Molecule-1, also known as HAVCR-1 (Hepatitis A virus cellular receptor 1), belongs to the cell-surface protein of immunoglobulin superfamily involved in the phagocytosis by acting as scavenger receptor epithelial cells. The study focused on pinpointing the mechanisms and genes that interact with KIM-1. METHODS: This in-silico study was done from March 2019 to December 2019. The Enrichment and protein-protein interaction (PPI) network carefully choose proteins. In addition, the diagramed gene data sets were accomplished using FunRich version 3.1.3. It was done to unveil the proteins that may affect the regulation of HAVCR1 or may be regulated by this protein. These genes were then further considered in pathway analysis to discover the dysregulated pathways in diabetic nephropathy. The long list of differentially expressed genes is meaningless without pathway analysis. RESULTS: Critical pathways that are dysregulated in diabetic nephropathy patients have been identified. These include Immune System (Total = 237, P < 0.05), Innate Immune System (Total = 140, P < 0.05), Cytokine Signaling Immune system (Total = 116, P < 0.05), Adaptive Immune System (Total = 85) and Neutrophil degranulation (Total = 78). CONCLUSION: The top 5 genes that are interacting directly with HIVCR1 include CASP3, CCL2, SPP1, B2M, and TIMP1 with degrees 161, 144, 108, 107, and 105 respectively for Immune system pathways (Innate Immune System, Cytokine Signaling Immune system, Adaptive Immune System and Neutrophil degranulation).

Thrombotic thrombocytopenia following ChAdOx1 nCov-19 vaccination.

Serious thromboembolic events with concurrent thrombocytopenia, sometimes accompanied by bleeding, have occurred very rarely following administration of the ChAdOx1 nCoV-19 vaccine. We report the case of a 59-year-old male with an unremarkable medical history who presented to the emergency department with increasing breathlessness five days after receiving the first dose of ChAdOx1 nCov-19. The patient's blood results showed mild thrombocytopenia and a very high D-dimer, and a pulmonary embolism was confirmed through a CT pulmonary angiogram, which led to a provisional diagnosis of vaccine-induced immune thrombotic thrombocytopenia. The condition was then treated with immunoglobulin and intravenous argatroban in line with the guidance from the Expert Haematology Panel focussed on Vaccine-induced Thrombosis and Thrombocytopenia before conversion to apixaban.

Protective effect of magnesium acetyltaurate against endothelin-induced retinal and optic nerve injury.

Vascular dysregulation has long been recognized as an important pathophysiological factor underlying the development of glaucomatous neuropathy. Endothelin-1 (ET1) has been shown to be a key player due to its potent vasoconstrictive properties that result in retinal ischemia and oxidative stress leading to retinal ganglion cell (RGC) apoptosis and optic nerve (ON) damage. In this study we investigated the protective effects of magnesium acetyltaurate (MgAT) against retinal cell apoptosis and ON damage. MgAT was administered intravitreally prior to, along with or after administration of ET1. Seven days post-injection, animals were euthanized and retinae were subjected to morphometric analysis, TUNEL and caspase-3 staining. ON sections were stained with toluidine blue and were graded for neurodegenerative effects. Oxidative stress was also estimated in isolated retinae. Pre-treatment with MgAT significantly lowered ET1-induced retinal cell apoptosis as measured by retinal morphometry and TUNEL staining. This group of animals also showed significantly lesser caspase-3 activation and significantly reduced retinal oxidative stress compared to the animals that received intravitreal injection of only ET1. Additionally, the axonal degeneration in ON was markedly reduced in MgAT pretreated animals. The animals that received MgAT co- or post-treatment with ET1 also showed improvement in all parameters; however, the effects were not as significant as observed in MgAT pretreated animals. The current study showed that the intravitreal pre-treatment with MgAT reduces caspase-3 activation and prevents retinal cell apoptosis and axon loss in ON induced by ET1. This protective effect of ET1 was associated with reduced retinal oxidative stress.

Light scattering by magnetoelectrically gyrotropic sphere with unit relative permittivity and relative permeability.

An exact transition matrix was formulated for electromagnetic scattering by a sphere made of a magnetoelectrically gyrotropic material with unit relative permittivity and relative permeability. The total scattering and forward scattering efficiencies are lower when the magnetoelectric gyrotropy vector of the sphere is either coparallel or antiparallel to the electric field or magnetic field of an incident plane wave than when the magnetoelectric gyrotropy vector is parallel to the propagation vector of the incident plane wave. Backscattering is absent when the propagation vector is either coparallel or antiparallel to the magnetoelectric gyrotropy vector.

Scattering of an electromagnetic plane wave by a homogeneous sphere made of an orthorhombic dielectric-magnetic material.

An exact transition matrix was formulated for electromagnetic scattering by an orthorhombic dielectric-magnetic sphere whose permeability dyadic is a scalar multiple of its permittivity dyadic. Calculations were made for plane waves incident on the sphere. As the size parameter increases, the role of anisotropy evolves; multiple lobes appear in the plots of the differential scattering efficiency in any scattering plane; the total scattering, extinction, and forward-scattering efficiencies exhibit a prominent maximum each; and the absorption efficiency generally increases with weak undulations. Certain orientations of the sphere with respect to the directions of propagation and the electric field of the incident plane wave make it highly susceptible to detection in a monostatic configuration, whereas other orientations make it much less vulnerable to detection. Impedance match to the ambient free space decreases backscattering efficiency significantly, although anisotropy prevents null backscattering.

Scattering of an electromagnetic plane wave by a homogeneous sphere made of an orthorhombic dielectric-magnetic material: erratum.

A correction is given for an equation in [J. Opt. Soc. Am. A31, 89-100 (2014)10.1364/JOSAA.31.000089JOAOD61084-7529].

Polymodal therapy for high grade gliomas: a case report of favourable outcomes following intraoperative radiation therapy.

High grade gliomas, frequently with their infiltrative nature, often make the outcome from neurosurgical intervention alone unsatisfactory. It is recognized that adjuvant radiochemotherapy approaches offer an improved prognosis. For these reasons, we opted for surgical debulking, intraoperative radiation therapy (IORT) in combination with whole brain irradiation therapy and chemotherapy (temozolamide cycles) in the management of a 42 year-old lady with Glioblastoma Multiforme (GBM). Her troublesome symptoms improved after 3 months of this polymodal therapy and remained independently functional for more than two years.

Survey for cotton mealybug, Phenacoccus solenopsis (Tinsley) and its natural enemies.

Mealybug was considered to be a minor pest of cotton but it emerged as a major pest in 2006-2007 in North and Central zones. Extensive field surveys conducted in cotton fields during 2007-09 in Haryana, Rajasthan and Punjab in the North zone and Madhya Pradesh, Maharashtra and Gujarat in the Central zone indicated that Phenacoccus solenopsis was the only major species of mealybug recorded on cotton in North as well as Central zones except one location in Gujarat where Fenrrisia virgata Cockerrel was also recorded. Infestation of mealybug at most of the places in North and Central zones ranged from mild (10-20%) to high (40-60%) during 2007 and 2008 but reduced to traces in 2009. Extensive field survey indicated that Aenasius bambawalei Hayat (Chalcidodea: Encyrtidae), an indigenous parasitoid, played a key role in reducing the insect pestinfestation. The parasitoid was first recorded in Delhi in July 2008 and by 2009 it was found in most of the cotton growing districts of North and Central zones. Its natural parasitization on P solenopsis could reach more than 90% at many locations. This is the most successful example of biological control of mealybug. Along with this parasitoid, another parasitoid, Promuscidea unfasciativentris Girault (Chalcidodea: Aphelinidae), was also recorded at most of the locations in smaller proportions.

LINAC based radiosurgery and radiotherapy for neurosurgical diseases: what have we learnt so far.

BACKGROUND: Stereotactic radiosurgery uses a single fraction high dose radiation while stereotactic radiotherapy uses multifractionated lower dose focused radiation. MATERIALS AND METHODS: Radiosurgery used rigid CRW head frame while stereotactic radiotherapy utilized GTC or HNL relocatable frames. Stereotactic planning and radiation involved Radionics X-plan and LINAC system. RESULTS: Since December 2001, we have treated 83 lesions from 77 patients using either radiosurgery or fractionated stereotactic radiotherapy. Eighty six percent (86%) of our treated lesions showed favourable outcomes with median follow-up of 32 months (0-7 years). CONCLUSIONS: Our lessons from LINAC precision radiation therapy uphold its value as a promising and effective tool in treating a range of nervous system pathologies.

Post traumatic cerebral oedema in severe head injury is related to intracranial pressure and cerebral perfusion pressure but not to cerebral compliance.

This was a prospective cohort study, carried out in the Neuro Intensive Care Unit, Department of Neurosciences, Hospital Universiti Sains Malaysia, Kubang Kerian Kelantan. The study was approved by the local ethics committee and was conducted between November 2005 and September 2007 with a total of 30 patients included in the study. In our study, univariate analysis showed a statistically significant relationship between mean intracranial pressure (ICP) as well as cerebral perfusion pressure (CPP) with both states of basal cistern and the degree of diffuse injury and oedema based on the Marshall classification system. The ICP was higher while CPP and compliance were lower whenever the basal cisterns were effaced in cases of cerebral oedema with Marshall III and IV. In comparison, the study revealed lower ICP, higher mean CPP and better mean cerebral compliance if the basal cisterns were opened or the post operative CT brain scan showed Marshall I and II. These findings suggested the surgical evacuation of clots to reduce the mass volume and restoration of brain anatomy may reduce vascular engorgement and cerebral oedema, therefore preventing intracranial hypertension, and improving cerebral perfusion pressure and cerebral compliance. Nevertheless the study did not find any significant relationship between midline shifts and mean ICP, CPP or cerebral compliance even though lower ICP, higher CPP and compliance were frequently observed when the midline shift was less than 0.5 cm. As the majority of our patients had multiple and diffuse brain injuries, the absence of midline shift did not necessarily mean lower ICP as the pathology was bilateral and even when after excluding the multiple lesions, the result remained insignificant. We assumed that the CT brain scan obtained after evacuation of the mass lesion to assess the state basal cistern and classify the diffuse oedema may prognosticate the intracranial pressure and cerebral perfusion pressure thus assisting in the acute post operative management of severely head injured patients. Hence post operative CT brain scans may be done to verify the ICP and CPP readings postoperatively. Subsequently, withdrawal of sedation for neurological assessment after surgery could be done if the CT brain scan showed an opened basal cistern and Marshall I and II coupled with ICP of less than 20 mmHg.

Pre-heating of components in cemented total hip arthroplasty.

Fatigue fractures which originate at stress-concentrating voids located at the implant-cement interface are a potential cause of septic loosening of cemented femoral components. Heating of the component to 44 degrees C is known to reduce the porosity of the cement-prosthesis interface. The temperature of the cement-bone interface was recorded intra-operatively as 32.3 degrees C. A simulated femoral model was devised to study the effect of heating of the component on the implant-cement interface. Heating of the implant and vacuum mixing have a synergistic effect on the porosity of the implant-cement interface, and heating also reverses the gradients of microhardness in the mantle. Heating of the implant also reduces porosity at the interface depending on the temperature. A minimum difference in temperature between the implant and the bone of 3 degrees C was required to produce this effect. The optimal difference was 7 degrees C, representing a balance between maximal reduction of porosity and an increased risk of thermal injury. Using contemporary cementing techniques, heating the implant to 40 degrees C is recommended to produce an optimum effect.

Risk stratification of Barrett's esophagus: updated prospective multivariate analysis.

OBJECTIVES: Prospective evaluation of Barrett's esophagus (BE) in order to determine what demographic, endoscopic, and histologic features are predictive of the prevalence and incidence of Barrett's high-grade dysplasia (HGD) and adenocarcinoma (Ca). METHODS: Newly diagnosed BE patients were entered into and followed in a standardized surveillance protocol. The following features were examined using either forward, stepwise multiple regression analysis, or Cox proportional hazards to determine their ability to predict the presence of HGD or Ca at index BE diagnosis as well as their ability to predict progression of BE during follow-up: age, race, gender, length of BE in cm, size of a hiatal hernia, severity of dysplasia at index diagnosis as well as during surveillance, gastric Helicobacter pylori infection status, and type of medical acid-reflux treatment. RESULTS: A total of 550 patients were diagnosed with BE over the study period. Stepwise multiple regression analysis showed three factors significantly associated with index diagnosis of HGD or Ca: hiatal hernia (larger size), Barrett's length (longer length), and absence of H. pylori infection. Three hundred and twenty-four BE entered the surveillance protocol. Cox proportional hazards models revealed a significant and independent association for five factors predictive of the time to progression of BE: presence of dysplasia at index diagnosis (p < 0.001), severity of dysplasia during surveillance (p < 0.001), length of Barrett's epithelium (p= 0.012), size of hiatal hernia (p= 0.006), and gastric H. pylori infection status (p= 0.023). CONCLUSIONS: Endoscopic and histologic features of BE at initial diagnosis are predictive of index HGD and cancer as well as with risk of BE progression.

Presence of telomerase activity with undetectable p16 gene mutation in Malaysian patients with brain tumor.

Recent study has shown that activation of the telomerase and p16 gene mutation are both necessary for tumorigenesis. Our objectives were to detect telomerase activity and investigate the possibility of p16 gene mutations in various types of brain tumor. We analyzed 23 tumor tissues collected in 2000 to 2002. Telomerase activity was detected by a TRAP assay using a TRAPEZE Telomerase Detection Kit (Intergen, Co). PCR-SSCP (Single Strand Conformation Polymorphism) analysis was performed to screen for p16 gene mutation at exon 1 and 2. The activity was detected in 26.1% of the brain tumor samples and mostly present in high-grade tumors. There was a significant association between telomerase activity status and tumor grade but not with patient criteria. Telomerase activity was detected in the analyzed tumors, supporting the fact that activation of telomerase is an important feature for tumorigenesis. There was no mobility shift of p16 gene using SSCP and suggested no mutation at exon 1 and 2 occurred in all samples. These results suggest that another mechanism of p16 gene alterations could be involved and associated with detectable telomerase activity in the progression of tumors.

Mutations of the p53 gene in gliomas from Malay patients.

This is the first investigation performed to detect the presence of the p53 mutation in Malay patients with gliomas. The p53 gene was amplified using polymerase chain reaction (PCR) from 33 fresh-frozen tumour tissues from patients histologically confirmed as glioma. Four hot spot areas that lie between exon 5 to 8 were screened for mutation by mean of non-isotopic "cold" single strand conformation polymorphism (SSCP) analysis and direct sequencing. The frequency of p53 gene mutation in gliomas examined was 33% (11 of 33). Five (45.5%) cases had mutation in exon 7, four (36.4%) had mutation in exon 8 and two (18.1%) had mutation in exon 6. Seven (63.6%) of 11 mutations were single nucleotide point mutations of which 5 were missense mutations, 1 was nonsense mutation and 1 was, silent mutation. Three (27.3%) showed insertion mutation and 1 (9.1%) showed deletion mutation. Of the point mutations, 57.1% were transitions and 42.9% were transversions. These results suggested that p53 mutations frequently occur in gliomas and this gene does play an important role in the tumourigenesis process of Malay patients with brain tumours.

Fusarium osteomyelitis of the foot in a patient with diabetes mellitus.

Diabetic foot osteomyelitis is among the most common and serious complications in patients with diabetes mellitus. It is often a polymicrobial infection. We report the first case of foot osteomyelitis in a diabetic patient caused by Fusarium solani.

Apoptosis is required for the proper formation of the ventriculo-arterial connections.

The role of apoptosis in cardiac morphogenesis has not been directly tested. Cardiomyocyte apoptosis is prevalent during the remodeling of the embryonic chicken cardiac outflow tract (OFT) in the transition from a single to a dual circulation. We tested the hypothesis that OFT cardiomyocyte apoptosis drives the shortening and rotation of the embryonic cardiac OFT and is required to achieve the mature ventriculo-arterial configuration. Chick embryos were treated with the peptide Caspase inhibitors zVAD-fmk or DEVD-cho at HH stages 15-20 (looped heart). Morphology of control and experimental embryos was assessed at HH stage 35, at which time the control hearts have developed a dual circulation. Infection of the hearts with a recombinant adenovirus expressing green fluorescent protein was used to follow the fate of the OFT cardiomyocytes. Affected embryos displayed abnormal persistence of a long infundibulum (OFT myocardial remnant) beneath the great vessels, indicating failure of OFT shortening. In some instances, the infundibulum connected both great vessels to the right ventricle in a side-by-side arrangement with transposition of the aorta, indicating a failure of rotation of the OFT, and modeling human congenital double outlet right ventricle. Defects were also observed at other sites in the heart where apoptosis is prevalent, such as in the formation of the cardiac valves and trabeculae. To more specifically target the apoptosis of the OFT cardiomyocytes, recombinant adenovirus was used to express the X-linked inhibitor of apoptosis protein in these cells. This resulted in an effect on outflow tract shortening and rotation similar to that of the peptide inhibitors, while the effects on the other cardiac structures were not observed. These results demonstrate that elimination of OFT cardiomyocytes by apoptosis is necessary for the proper formation of the ventriculo-arterial connections, and suggest apoptosis as a potential target of teratogens and genetic defects that are associated with congenital human conal heart defects.

Comparison of four methods for identifying Streptococcus pneumoniae.

Four methods (bile solubility, optochin, latex agglutination, and DNA probe) were compared for identification of clinical isolates of Streptococcus pneumoniae. Of 209 isolates tested, 151 (Group I) were selected based on typical colony morphology of S. pneumoniae, while 58 (Group II) were selected on the basis of alpha-hemolysis alone. Using the DNA probe as a reference method, 141 isolates from Group I and 10 from Group II were identified as S. pneumoniae. The optochin disk test and the latex agglutination test both exhibited a 100% sensitivity and specificity for Group I isolates; bile solubility identified all but 1 isolate in this group. For Group II isolates, the sensitivity and specificity of optochin testing was 100%, 80 and 94% for latex and 80 and 100% for bile. The results of this study indicate that all methods tested give reliable results for isolates with typical colony morphology of S. pneumoniae. Bile solubility and latex may not be as reliable when testing alpha-hemolytic colonies without colony morphology typical S. pneumoniae.