Effect of Intravitreal Ranibizumab in the Treatment of Peripapillary Choroidal Neovascularisation

Intravitreal ranibizumab therapy is widely used in treatment of subfoveal choroidal neovascularisation (CNV) in age-related macular degeneration. We wanted to study the effect of intravitreal ranibizumab therapy in peripapillary CNV. A prospective recording of treatment outcomes in twelve eyes (12 patients) with peripapillary CNV with intravitreal injections of ranibizumab was performed. The patients received a series of 3 injections 4–6 weeks apart, and then a new ophthalmic examination was made including OCT and further therapy was given if the peripapillary CNV was still active. Nine patients had idiopathic peripapillary CNV, and in 3 patients it was associated to age-related macular degeneration. Followup had to be at least 6 months. The mean follow-up time was 15.9 (range 9–27) months and the mean number of injections 6.2 (3–10). In 10 patients treatment had resulted in an inactivation of the peripapillary CNV, but 3 of them had reactivation, while 2 patients had no inactivation. Currently, 5 patients are continuous to receive treatment. VA improved in 10 patients. Intravitreal ranibizumab therapy appears to be effective in patients with peripapillary CNV, but in some cases there is repeated reactivation or continuous activity of the peripapillary CNV

Optical Coherence Tomography Angiography of Purtscher Retinopathy after Severe Traffic Accident in 16-Year-Old Boy

Purpose. To describe optical coherence tomography (OCT) angiography (OCTA) in a case of Purtscher retinopathy. Methods. A 16-year-old male underwent ophthalmological examination including color fundus photography, spectral domain OCT, OCTA, and microperimetry. Examination was performed 10 days, 1 month, and 6 months after the trauma. Diagnosis was based on the characteristic clinical presentation. Patients. A single patient case. Results. Only the right eye was affected, and all examinations of the left eye were normal. The visual acuity of the right eye was 0.03 (Snellen equivalent) at 10 days and at one month, improving to 0.16 at 6 months. The imaging confirmed the findings of Purtscher retinopathy with ischemic whitening of the retina and retinal hemorrhages and thickened inner retina on OCT. Microperimetry showed reduced sensitivity in the central macula of the right eye. OCTA revealed nonperfusion in both the superficial and the deep retinal capillary plexus of the right eye. Conclusion. The OCTA in traumatic Purtscher retinopathy following traffic accident showed nonperfusion in both the superficial and the deep capillary plexus of the retina. OCTA is a valuable noninvasive diagnostic examination in Purtscher retinopathy, and fluorescein angiography became redundant in this case

Corneal Toxicity Following Exposure to <i>Asclepias Tuberosa</i>

PURPOSE: To present a case of corneal toxicity following exposure to milky plant latex from Asclepias tuberosa. METHODS: A 70-year-old female presented with blurred vision and pain in her left eye after handling an Ascepias tuberosa. Clinical examination revealed a corneal stromal oedema with small epithelial defects. The corneal endothelium was intact and folds in Descemets membrane were observed. The oedema was treated with chloramphenicol, dexamethasone and scopolamine. RESULTS: The corneal oedema had appeared after corneal exposure to the plant, Asclepias tuberosa, whose latex contains cardenolides that inhibit the Na(+)/ K(+)-ATPase in the corneal endothelium. The oedema resolved after 96 hours. After nine months the best corrected visual acuity was 20/20. CONCLUSION: Corneal toxicity has previously been reported for plants of the Asclepias family. This is a rare case describing severe corneal toxicity caused by exposure to latex from Asclepias tuberosa. Handling of plants of the Asclepias family should be kept as a differential diagnosis in cases of acute corneal toxicity

Evaluation of anti bacterial activity of punica granatum peels extracts, on growth of gram-positive bacteria isolated from clinical samples

Thirty samples were collected from patients (10-45) years old, suffered from tonsillitis,pharyngitis, infected wounds, acne &amp; Bronchitis. Gram &ndash;positive bacteria were isolated from these samples, and diagnosed, of which, Staphylococcus aureus ( 50%) and Staphylococcus epidermidis (16.66%), Streptococcus pyogenes (13.34%), Streptococcus pneumoniae (10%) and Micrococcus spp (10%). Alcoholic and water extracts of the punica granatum(Pomegranate) peels as well as the dried powders were prepared, the effect of these extracts were studied against these isolates. The antimicrobial susceptibility tests of the extracts were determined by Kirby- Bauer method and the MICs were determined. The antibacterial activity of punica granatum(Pomegranate) peels was determined. The alcoholic extract showed more potent inhibitory effect on the isolates than water extract, and the best effect was on the growth of Staphylococcus epidermidis followed by Staphylococcus aureus , Micrococcus spp, Streptococcus pyogenes and Streptococcus pneumoniae. The zone of inhibition was (17- 23mm) for alcoholic extract and( 12-23mm) for watery extract. The antibacterial activity of pomegranate peels extracts should make it useful for treatment of wounds, skin infections, tonsillitis and pharyngitis caused by the above bacteria

Diagnostic value of H3F3A mutations in giant cell tumour of bone compared to osteoclast-rich mimics

Driver mutations in the two histone 3.3 (H3.3) genes, H3F3A and H3F3B, were recently identified by whole genome sequencing in 95% of chondroblastoma (CB) and by targeted gene sequencing in 92% of giant cell tumour of bone (GCT). Given the high prevalence of these driver mutations, it may be possible to utilise these alterations as diagnostic adjuncts in clinical practice. Here, we explored the spectrum of H3.3 mutations in a wide range and large number of bone tumours (n 5 412) to determine if these alterations could be used to distinguish GCT from other osteoclast-rich tumours such as aneurysmal bone cyst, nonossifying fibroma, giant cell granuloma, and osteoclast-rich malignant bone tumours and others. In addition, we explored the driver landscape of GCT through whole genome, exome and targeted sequencing (14 gene panel). We found that H3.3 mutations, namely mutations of glycine 34 in H3F3A, occur in 96% of GCT. We did not find additional driver mutations in GCT, including mutations in IDH1, IDH2, USP6, TP53. The genomes of GCT exhibited few somatic mutations, akin to the picture seen in CB. Overall our observations suggest that the presence of H3F3A p.Gly34 mutations does not entirely exclude malignancy in osteoclast-rich tumours. However, H3F3A p.Gly34 mutations appear to be an almost essential feature of GCT that will aid pathological evaluation of bone tumours, especially when confronted with small needle core biopsies. In the absence of H3F3A p.Gly34 mutations, a diagnosis of GCT should be made with caution

Identifying Immunological and Clinical Predictors of COVID-19 Severity and Sequelae by Mathematical Modeling

Since its emergence as a pandemic in March 2020, coronavirus disease (COVID-19) outcome has been explored via several predictive models, using specific clinical or biochemical parameters. In the current study, we developed an integrative non-linear predictive model of COVID-19 outcome, using clinical, biochemical, immunological, and radiological data of patients with different disease severities. Initially, the immunological signature of the disease was investigated through transcriptomics analysis of nasopharyngeal swab samples of patients with different COVID-19 severity versus control subjects (exploratory cohort, n=61), identifying significant differential expression of several cytokines. Accordingly, 24 cytokines were validated using a multiplex assay in the serum of COVID-19 patients and control subjects (validation cohort, n=77). Predictors of severity were Interleukin (IL)-10, Programmed Death-Ligand-1 (PDL-1), Tumor necrosis factors-α, absolute neutrophil count, C-reactive protein, lactate dehydrogenase, blood urea nitrogen, and ferritin; with high predictive efficacy (AUC=0.93 and 0.98 using ROC analysis of the predictive capacity of cytokines and biochemical markers, respectively). Increased IL-6 and granzyme B were found to predict liver injury in COVID-19 patients, whereas interferon-gamma (IFN-γ), IL-1 receptor-a (IL-1Ra) and PD-L1 were predictors of remarkable radiological findings. The model revealed consistent elevation of IL-15 and IL-10 in severe cases. Combining basic biochemical and radiological investigations with a limited number of curated cytokines will likely attain accurate predictive value in COVID-19. The model-derived cytokines highlight critical pathways in the pathophysiology of the COVID-19 with insight towards potential therapeutic targets. Our modeling methodology can be implemented using new datasets to identify key players and predict outcomes in new variants of COVID-19

Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone

It is recognized that some mutated cancer genes contribute to the development of many cancer types, whereas others are cancer type specific. For genes that are mutated in multiple cancer classes, mutations are usually similar in the different affected cancer types. Here, however, we report exquisite tumor type specificity for different histone H3.3 driver alterations. In 73 of 77 cases of chondroblastoma (95%), we found p.Lys36Met alterations predominantly encoded in H3F3B, which is one of two genes for histone H3.3. In contrast, in 92% (49/53) of giant cell tumors of bone, we found histone H3.3 alterations exclusively in H3F3A, leading to p.Gly34Trp or, in one case, p.Gly34Leu alterations. The mutations were restricted to the stromal cell population and were not detected in osteoclasts or their precursors. In the context of previously reported H3F3A mutations encoding p.Lys27Met and p.Gly34Arg or p.Gly34Val alterations in childhood brain tumors, a remarkable picture of tumor type specificity for histone H3.3 driver alterations emerges, indicating that histone H3.3 residues, mutations and genes have distinct functions

‘Gatekeepers’ of Islamic financial circuits: Analysing urban geographies of the global Shari’a elite

This paper analyses the importance of 'Shari'a scholars' in the Islamic Financial Services (IFS) sector, which has been a growing global practice since the 1970s. Based on Shari'a Law, IFS firms provide banking, finance and insurance respecting faith-based prohibitions on interest, speculation and risk taking. Although IFS firms operate across a variety of scales and involve a range of actors, this paper focuses on the transnational capacities of Shari'a experts employed by IFS firms. These scholars use their extensive knowledge of Shari'a Law to assess the 'Islamic' character of a firm's operations, and assist the development of Shari'a-compliant products. As they embody necessary entry-points into Islamic circuits of knowledge and authority, members of what we dub the 'global Shari'a elite' can be regarded as 'gatekeepers' of Islamic financial circuits. Drawing on a comprehensive data source we present a geographical analysis of Shari'a board membership, nationality and educational background of 253 Shari'a scholars. The results show that the global Shari'a elite connects a limited number of IFS hubs (e. g. Dubai, Kuala Lumpur, Kuwait City, Manama, and London) to knowledge and authority networks falling outside 'mainstream' business and service spheres

Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021

Background: Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050. Methods: Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. Findings: In the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8–63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0–45·0] in 2050) and south Asia (31·7% [29·2–34·1] to 15·5% [13·7–17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4–40·3) to 41·1% (33·9–48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6–25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5–43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5–17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7–11·3) in the high-income super-region to 23·9% (20·7–27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5–6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2–26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [–0·6 to 3·6]). Interpretation: Globally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions

Experimental Investigations on the Strength and Serviceability of Biaxial Hollow Concrete Slabs

Biaxial hollow slab is a reinforced concrete slab system with a grid of internal spherical voids included to reduce the self-weight. This paper presents an experimental study of behavior of one-way prestressed concrete bubbled slabs. Twelve full-scale one-way concrete slabs of (3000mm) length with rectangular cross-sectional area of (460mm) width and (150mm) depth. Different parameters like type of specimen (solid or bubbled slabs), type of reinforcement (normal or prestress), range of PPR and diameter of plastic spheres (100 or 120mm) are considered. Due to the using of prestressing force in bubbled slabs (with ratio of plastic sphere diameter D to slab thickness H, D/H=0.67), the specimens showed an increase in ultimate load capacity ranging between (79.3% and 125%) and a decrease in the deflection at service load of about (9.8% to 12%) with respect to the control bubbled reinforced concrete slab. Also, it is found that, the bubbled slabs have about (79% to 86%) of the ultimate load capacity of a similar reference solid slab. At the same time the influence of voids present in the bubbled slabs is reflected in a decrease in the first cracking load by about (14.8% to 29.6%) in comparison with solid slabs