Dense Deposit Disease: A 29-Years Electron Microscopy Experience

Introduction: Dense Deposit Disease (DDD) is a devastating renal disease that leads to renal failure within 10 years of diagnosis in about half of affected patients. In this study, we evaluated the relative prevalence and pathological features of DDD diagnosed at our center over a 29 years period.Methods: We reviewed the clinical and pathological features of all cases of DDD diagnosed at the Electron Microscopy Unit of Ain Shams University (ASUSH) between January 1983 and December 2011.Results: From a total of 3283 renal biopsies, 33 (1%) were diagnosed with DDD (10 children and 23 adults). Nephrotic syndrome was the predominant clinical presentation of DDD (51.5%), and was commoner in children than adults (80% vs. 43%, p=0.03). Capillary wall thickening was seen in all cases (100%). Crescents were more commonly seen in children than adults (70% vs. 21.7%, p=0.008) while interstitial fibrosis was more commonly seen in adults (78.3% vs. 40%, p=0.03). The commonest histological pattern seen under light microscopy was membranoproliferative (27.3%), followed by crescentic (21.2%), membranous (21.2%), diffuse proliferative (18.2%), lobular (6.1%) and mesangial proliferative (6.1%) patterns. Immunohistochemistry was available for 25 cases and showed intense linear staining for C3 along capillary walls. Electron microscopic examination revealed glomerular basement membrane (GBM) thickening and intra-membranous and tubular basement membrane deposits in all cases (100%).Conclusion: DDD is a rare disease in Egypt, found in only 1% of renal biopsies. Pathological features of the disease differ between adults and children; children have predominantly glomerular damage whereas tubule-interstitial lesions are more often encountered in adults.Key words: Dense Deposit Disease; Electron Microscopy; Membranoproliferative Glomerulonephritis; Nephrotic Syndrom

GPT-FL: Generative Pre-trained Model-Assisted Federated Learning

In this work, we propose GPT-FL, a generative pre-trained model-assisted federated learning (FL) framework. At its core, GPT-FL leverages generative pre-trained models to generate diversified synthetic data. These generated data are used to train a downstream model on the server, which is then fine-tuned with private client data under the standard FL framework. We show that GPT-FL consistently outperforms state-of-the-art FL methods in terms of model test accuracy, communication efficiency, and client sampling efficiency. Through comprehensive ablation analysis, we discover that the downstream model generated by synthetic data plays a crucial role in controlling the direction of gradient diversity during FL training, which enhances convergence speed and contributes to the notable accuracy boost observed with GPT-FL. Also, regardless of whether the target data falls within or outside the domain of the pre-trained generative model, GPT-FL consistently achieves significant performance gains, surpassing the results obtained by models trained solely with FL or synthetic data

Enhanced adsorption of cationic and anionic dyes from aqueous solutions by polyacid doped polyaniline

A new high surface area polyaniline (PANI) adsorbent was synthesized by matrix polymerization of aniline in the presence of a polyacid, poly(2-acrylamido-2-methyl-1-propanesulfonic acid) (PAMPSA). Morphological and physicochemical properties of PANI-PAMPSA were characterized by field emission scanning electron microscope (FESEM), Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), nitrogen adsorption/desorption and zeta potential measurement. Adsorption properties were evaluated using methylene blue (MB) and rose bengal (RB) as model dyes.The results showed that PANI-PAMPSA obtained a well-defined porous structure with a specific surface area (126 m2 g−1) over 10 times larger than that of the emeraldine base PANI (PANI-EB) (12 m2 g−1). The maximum adsorption capacities were 466.5 mg g−1 for MB and 440.0 mg g−1 for RB, higher than any other PANI-based materials reported in the literature. The FTIR analysis and zeta potential measurement revealed that the adsorption mechanisms involved π-π interaction and electrostatic interaction. The adsorption kinetics were best described by a pseudo-second-order model, and the adsorption isotherms followed the Langmuir model. The thermodynamic study indicated that the adsorption was a spontaneous endothermic process. Overall, the convenient synthesis and the high adsorption capacity make PANI-PAMPSA a promising adsorbent material for dye removal

Children and older adults exhibit distinct sub-optimal cost-benefit functions when preparing to move their eyes and hands

"© 2015 Gonzalez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited"Numerous activities require an individual to respond quickly to the correct stimulus. The provision of advance information allows response priming but heightened responses can cause errors (responding too early or reacting to the wrong stimulus). Thus, a balance is required between the online cognitive mechanisms (inhibitory and anticipatory) used to prepare and execute a motor response at the appropriate time. We investigated the use of advance information in 71 participants across four different age groups: (i) children, (ii) young adults, (iii) middle-aged adults, and (iv) older adults. We implemented 'cued' and 'non-cued' conditions to assess age-related changes in saccadic and touch responses to targets in three movement conditions: (a) Eyes only; (b) Hands only; (c) Eyes and Hand. Children made less saccade errors compared to young adults, but they also exhibited longer response times in cued versus non-cued conditions. In contrast, older adults showed faster responses in cued conditions but exhibited more errors. The results indicate that young adults (18 -25 years) achieve an optimal balance between anticipation and execution. In contrast, children show benefits (few errors) and costs (slow responses) of good inhibition when preparing a motor response based on advance information; whilst older adults show the benefits and costs associated with a prospective response strategy (i.e., good anticipation)

Broad targeting of resistance to apoptosis in cancer

Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer

Evasion of anti-growth signaling: a key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds

The evasion of anti-growth signaling is an important characteristic of cancer cells. In order to continue to proliferate, cancer cells must somehow uncouple themselves from the many signals that exist to slow down cell growth. Here, we define the anti-growth signaling process, and review several important pathways involved in growth signaling: p53, phosphatase and tensin homolog (PTEN), retinoblastoma protein (Rb), Hippo, growth differentiation factor 15 (GDF15), AT-rich interactive domain 1A (ARID1A), Notch, insulin-like growth factor (IGF), and Krüppel-like factor 5 (KLF5) pathways. Aberrations in these processes in cancer cells involve mutations and thus the suppression of genes that prevent growth, as well as mutation and activation of genes involved in driving cell growth. Using these pathways as examples, we prioritize molecular targets that might be leveraged to promote anti-growth signaling in cancer cells. Interestingly, naturally-occurring phytochemicals found in human diets (either singly or as mixtures) may promote anti-growth signaling, and do so without the potentially adverse effects associated with synthetic chemicals. We review examples of naturally-occurring phytochemicals that may be applied to prevent cancer by antagonizing growth signaling, and propose one phytochemical for each pathway. These are: epigallocatechin-3-gallate (EGCG) for the Rb pathway, luteolin for p53, curcumin for PTEN, porphyrins for Hippo, genistein for GDF15, resveratrol for ARID1A, withaferin A for Notch and diguelin for the IGF1-receptor pathway. The coordination of anti-growth signaling and natural compound studies will provide insight into the future application of these compounds in the clinical setting

The Persisting Burden of Intracerebral Haemorrhage: Can Effective Treatments Be Found?

Colin Josephson, Rustam Al-Shahi Salman, and colleagues discuss the effectiveness of treatments for intracerebral haemorrhage

Biological activities for 'Ficus carica' latex for potential therapeutics in Human Papillomavirus (HPV) related cervical cancers

Abstract Infection caused by high-risk human papillomaviruses (HPVs) are implicated in the aetiology of cervical cancer. Although current methods of treatment for cervical cancer can ablate lesions, preventing metastatic disseminations and excessive tissue injuries still remains a major concern. Hence, development of a safer and more efficient treatment modality is of vital importance. Natural products from plants are one of the principal sources of precursors to lead compounds with direct pharmaceutical application across all disease classes. One of these plants is Ficus carica, whose fruit latex, when applied on HPV-induced skin warts, has shown potential as a possible cure for this virus related lesions. This study explores the in vitro biological activities of fig latex and elucidates its possible mechanisms of action on cervical cancer cell lines CaSki and HeLa positive for HPV type 16 and 18, respectively. Our data shows that fig latex inhibits properties that are associated with HPV-positive cervical cancer transformed cells such as rapid growth and invasion and substantially downregulated the expression of p16 and HPV onco-proteins E6, E7. These findings suggest Ficus carica latex has the potential to be used in the development of therapeutic modalities for the possible treatment, cure and prevention of HPV related cervical cancer