Modulation of Aß 16-22 aggregation by glucose.

The self-assembly of amyloid-beta (Aß) peptides into fibrillar structures in the brain is a signature of Alzheimer's disease. Recent studies have reported correlations between Alzheimer's disease and type-2 diabetes. Structurally, hyperglycemia induces covalent protein crosslinkings by advanced glycation end products (AGE), which can affect the stability of Aß oligomers. In this work, we leverage physics-based coarse-grained molecular simulations to probe alternate thermodynamic pathways that affect peptide aggregation propensities at varying concentrations of glucose molecules. Similar to previous experimental reports, our simulations show a glucose concentration-dependent increase in Aß aggregation rates, without changes in the overall secondary structure content. We discovered that glucose molecules prefer partitioning onto the aggregate-water interface at a specific orientation, resulting in a loss of molecular rotational entropy. This effectively hastens the aggregation rates, as peptide self-assembly can reduce the available surface area for peptide-glucose interactions. This work introduces a new thermodynamic-driven pathway, beyond chemical cross-linking, that can modulate Aß aggregation.

Clinicopathologic Features of Metaplastic Breast Carcinoma: Experience From a Tertiary Cancer Center of North India.

Introduction Metaplastic breast cancer (MBC) is a rare malignancy that accounts for < 1% of all breast cancers. The aim of this study is to evaluate the clinicopathologic characteristics of MBC patients treated at a tertiary cancer center. Materials and methods In this study, the authors retrospectively analyzed the prospectively maintained data of MBC patients treated at a tertiary cancer care center in North India between January 2019 and July 2022. Results A total of 28 MBCs were identified. The median age of presentation was 47 years (range 27-81 years). Seventeen patients (60.7%) presented with clinical T3/T4 disease, and axillary nodal involvement was detected in 11 patients (39.3%) at presentation. Two patients had metastatic disease at presentation. A preoperative diagnosis of MBC on core biopsy was attained in five patients (17.9%), and the most common histologic subtype was sarcomatoid carcinoma. Triple-negative receptor status was observed in 15 patients (53.6%). Six patients (21.4%) underwent upfront breast conservation surgery and another six (21.4%) upfront mastectomy. Thirteen patients (46.4%) underwent mastectomy following neoadjuvant therapy. Definitive axillary nodal metastasis was found in eight patients (32%). Following neoadjuvant chemotherapy, five patients (35.7%) had stable disease, disease progression was evident in five patients (35.7%), partial response in four patients (28.6%), and no patient evinced complete response. Adjuvant postoperative radiation therapy was administered in 16 patients (57.1%). At a median follow-up of 13.2 months (range 4-26 months), 16 patients (57.1%) were alive with no evidence of disease, one patient (3.6%) was alive with disease, nine patients (32.1%) died of disease, and two patients (7.2%) died of other causes. One patient suffered from locoregional recurrence and nine patients developed distant metastasis. Conclusion MBC is an infrequent entity among breast carcinomas in India, which is similar to the reports of MBC worldwide. The diagnosis of MBC is difficult and requires the use of immunohistochemistry. Most of the cases in our study presented with a larger tumor size; however, they displayed a relatively lower incidence of nodal involvement as well as hormone receptor negativity. Being a rare and heterogeneous disease, large-scale studies are essential for better understanding and management of these tumors.

Preoperative diagnosis of renal angiomyolipoma with fine needle aspiration cytology: a report of 3 cases.

BACKGROUND: Angiomyolipoma is a rare benign neoplasm, commonly involving the kidney. Preoperative diagnosis on fine needle aspiration cytology can confirm the diagnosis, reducing the chances of unnecessary surgery. CASES: We studied cases of renal angiomyolipoma (AML) presenting within 1 year with palpable renal masses confirmed on ultrasound to be of renal origin. Fine needle aspiration cytology (FNAC) smears showed a few cohesive syncytial fragments with adipocytes, spindle cells and isolated single cells with foamy cytoplasm; a diagnosis of AML was made. The diagnosis was confirmed on histopathology, which showed mature adipose tissue, tortuous and thick-walled blood vessels lacking elastic tissue lamina and bundles of smooth muscles that seemed to emanate from the blood vessels. CONCLUSION: A preoperative diagnosis of renal AML is of great importance for correct management. In fact, when the lesion is small and asymptomatic, a conservative approach may be considered. Partial nephrectomy is possible with masses < 5 cm. Preoperative FNAC along with computed tomographic findings and immunocytochemical analysis of FNAC smears with HNB-45 can confirm the diagnosis of AML, thus preventing unindicated nephrectomy.

Comparative study of microscopic detection methods and haematological changes in malaria.

Quantitative buffy coat (QBC) technique, thick smears, thin smears and conventional buffy coat smears were compared for malarial parasite detection. Of 200 blood samples studied, 70 (35%) samples were positive by QBC technique, 62 (31%) samples by thick smears, 50 (25%) samples by thin smears and only 34 (17%) samples were positive by conventional buffy coat technique. 8 (4%) samples detected by QBC technique alone, had low parasitic index. Haematological analysis was performed on samples positive for malarial parasite. Anaemia was present in 66 (94.28%) samples of which 37 (56.06%) were Plasmodium falciparum, 21 (31.81%) were Plasmodium vivax and 8 (12.12%) had mixed infection (Plasmodium falciparum and Plasmodium vivax). 35 (50%) cases showed normocytic normochromic anaemia. Majority of the samples showed normal total and differential leukocyte count. Thrombocytopenia was found in 49 (70%) samples of which 33 (67.34%) were Plasmodium falciparum.