Astrocytic Redox Remodeling by Amyloid Beta Peptide

Abstract Astrocytes are critical for neuronal redox homeostasis providing them with cysteine needed for glutathione synthesis. In this study, we demonstrate that the astrocytic redox response signature provoked by amyloid beta (A-) is distinct from that of a general oxidant (tertiary-butylhydroperoxide [t-BuOOH]). Acute A- treatment increased cystathionine --synthase (CBS) levels and enhanced transsulfuration flux in contrast to repeated A- exposure, which decreased CBS and catalase protein levels. Although t-BuOOH also increased transsulfuration flux, CBS levels were unaffected. The net effect of A- treatment was an oxidative shift in the intracellular glutathione/glutathione disulfide redox potential in contrast to a reductive shift in response to peroxide. In the extracellular compartment, A-, but not t-BuOOH, enhanced cystine uptake and cysteine accumulation, and resulted in remodeling of the extracellular cysteine/cystine redox potential in the reductive direction. The redox changes elicited by A- but not peroxide were associated with enhanced DNA synthesis. CBS activity and protein levels tended to be lower in cerebellum from patients with Alzheimer's disease than in age-matched controls. Our study suggests that the alterations in astrocytic redox status could compromise the neuroprotective potential of astrocytes and may be a potential new target for therapeutic intervention in Alzheimer's disease. Antioxid. Redox Signal. 14, 2385-2397.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90483/1/ars-2E2010-2E3681.pd

Toxicity outcome of concurrent teletherapy and brachytherapy compared with teletherapy followed by brachytherapy in locally advanced carcinoma cervix

Background: Teletherapy and intracavitary brachytherapy are definitive treatment modalities for stages IIB to IVA cervical carcinoma. Globally, it is the second most common cancer among female. Majority of patients attend the hospital with locally advanced stage due to less screening facility and social stigma.Methods: This quasi-experimental study was conducted from January 2019 to June 2020 with a total of 76 patients. The patients were equally divided into two groups: A and B after obtaining their informed written consent.Results: Final follow up was given after completion of treatment at 24 weeks. Patients in both groups developed grade 1 gastrointestinal and genitourinary toxicities (10.5% versus 13.1%, 13.1% versus 15.7% in group A and B respectively). Two patients in group A and three patients in group B developed grade 2 gastrointestinal toxicities. In genitourinary toxicities, grade 2 toxicities were observed in two patients of group A and four patients of group B, (p>0.05). None developed grade 3 and 4 gastrointestinal and genitourinary toxicities. There were no statistically significant variations in treatment related toxicities between the two groups.Conclusions: Both gastrointestinal, genitourinary toxicities were comparable between two groups. The toxicities were acceptable and well tolerated.

Model pembinaan moderasi beragama era society 5.0 di perguruan tinggi (studi multikasus di Universitas Islam Negeri Maulana Malik Ibrahim Malang dan di Universitas Pendidikan Indonesia Bandung)

The purpose of this study is to analyze the approach to fostering religious moderation in tertiary institutions. The method used is a qualitative case study type method. Data collection techniques are carried out through interviews, observation and documentation. The data analysis technique used consists of three activity flows that occur simultaneously, namely; data reduction, data presentation, conclusion or verification. The results showed that the characteristics of cultivating religious moderation using general courses (MKU) and university specific courses (MKKU) were incorporated into the tri dharma activities of higher education. To implement it using a scientific approach, bersanad, and dissemination. The dominant aspect of the approach to fostering religious moderation is using dissemination at UIN Maulana Malik Ibrahim Malang. The dissemination of moderate Islamic values is explained in the course SLP, instilled in the introduction of campus academic culture (PBAK), and developed in student work practice (KKM)

Na+ and K+ ion imbalances in Alzheimer's disease

AbstractAlzheimer's disease (AD) is associated with impaired glutamate clearance and depressed Na+/K+ ATPase levels in AD brain that might lead to a cellular ion imbalance. To test this hypothesis, [Na+] and [K+] were analyzed in postmortem brain samples of 12 normal and 16 AD individuals, and in cerebrospinal fluid (CSF) from AD patients and matched controls. Statistically significant increases in [Na+] in frontal (25%) and parietal cortex (20%) and in cerebellar [K+] (15%) were observed in AD samples compared to controls. CSF from AD patients and matched controls exhibited no differences, suggesting that tissue ion imbalances reflected changes in the intracellular compartment. Differences in cation concentrations between normal and AD brain samples were modeled by a 2-fold increase in intracellular [Na+] and an 8–15% increase in intracellular [K+]. Since amyloid beta peptide (Aβ) is an important contributor to AD brain pathology, we assessed how Aβ affects ion homeostasis in primary murine astrocytes, the most abundant cells in brain tissue. We demonstrate that treatment of astrocytes with the Aβ 25–35 peptide increases intracellular levels of Na+ (~2–3-fold) and K+ (~1.5-fold), which were associated with reduced levels of Na+/K+ ATPase and the Na+-dependent glutamate transporters, GLAST and GLT-1. Similar increases in astrocytic Na+ and K+ levels were also caused by Aβ 1–40, but not by Aβ 1–42 treatment. Our study suggests a previously unrecognized impairment in AD brain cell ion homeostasis that might be triggered by Aβ and could significantly affect electrophysiological activity of brain cells, contributing to the pathophysiology of AD

Comparison of dosimetric parameters between intensity modulated and three-dimensional conformal radiotherapy planning for adjuvant therapy of gastric cancer

Background: Adjuvant chemoradiotherapy is the standard treatment for gastric carcinoma, but the optimal radiation modality remains uncertain. This study aimed to compare intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) in terms of dosimetry for adjuvant gastric cancer treatment. Methods: 21 patients with stage IIB-IIIC gastric cancer, treated between January and June 2021, underwent surgery followed by adjuvant chemoradiation with both IMRT and 3D-CRT plans. Dosimetric parameters were calculated for the planned target volume (PTV) and organs at risk (OAR). Results: Both IMRT and 3D-CRT provided comparable PTV coverage. However, IMRT significantly improved kidney sparing, reducing the mean V20 value by 23% (p=0.01) for the right kidney and 26% (p=0.02) for the left kidney compared to 3D-CRT. IMRT also decreased the mean irradiated volume for both kidneys and the liver, as well as the V30 value for the liver, although these differences were not statistically significant. The dosimetric parameters for the spinal cord were comparable between IMRT and 3D-CRT plans. Conclusions: IMRT demonstrated better kidney sparing compared to 3D-CRT in adjuvant radiotherapy for gastric cancer, while PTV coverage was similar. Long-term follow-up is necessary to assess clinical outcomes and local recurrence rates for both treatment plans

Pengaruh Saluran Distribusi dan Harga Produk terhadap Volume Penjualan Air Minum Dalam Kemasan (AMDK) Merek Wahdah Water pada CV. Syifa Water 5 In One di Kabupaten Gowa

Penelitian ini bertujuan untuk mengetahui Pengaruh Saluran Distribusi dan Harga Produk terhadap Volume Penjualan Air Minum Dalam Kemasan (AMDK) Merek Wahdah Water pada CV. Syifa Water 5 In One di Kabupaten Gowa. Populasi dalam Penelitian ini adalah konsumen CV. Syifa Water 5 In One yang melakukan minimal dua kali pembelian produk Air Minum Dalam Kemasan (AMDK) Merek Wahdah Water pada bulan November – Desember 2019. Jumlah sampel yang digunakan sebanyak 50 orang. Pengumpulan data dilakukan dengan menggunakan metode dokumentasi, kuesioner dan kajian pustaka. Teknis analisis data yang digunakan adalah analisis regresi linear berganda dengan menggunakan Statistical Product and Servise Solution (SPSS) v. 22. Persamaan regresi linear berganda menghasilkan persamaan Y = 3,379 + 0,258X1 + 0,568X2. Dengan demikian hasil penelitian ini menemukan bahwa secara simultan variabel Saluran Distribusi dan Harga Produk (X1 dan X2) berpengaruh positif terhadap Volume Penjualan (Y). Hasil analisis korelasi determinasi (R2 ) sebesar 0,454 yang menunjukkan bahwa 45,4 % variabel bebas yaitu X1 dan X2 berpengaruh atau mampu menjelaskan karakteristik variabel terikat (Y). Selisihnya 54,6 % dipengaruhi oleh variabel lain yang tidak diteliti. Hasil uji F menjelaskan bahwa variabel Saluran Distribusi dan Harga Produk berpengaruh signifikan terhadap variabel Volume Penjualan dengan nilai Fhitung (19,564) ˃ Ftabel (3.195) dengan taraf signifikansi 0,000 ˂ 0,05 dan hasil uji t menjelaskan bahwa variabel Saluran Distribusi (X1) dengan nilai 0,010 < 0,05 dan Harga Produk (X2) dengan nilai 0,000 < 0,05 memiliki pengaruh signifikan terhadap variabel Volume Penjualan. Kata Kunci : Saluran Distribusi, Harga Produk, Volume Penjuala

PENGARUH KUALITAS PELAYANAN TERHADAP KEPUASAN PELANGGAN PERUSAHAAN DAERAH AIR MINUM (PDAM) TIRTA JENEBERANG IKK BORONGLOE DI KABUPATEN GOWA

Penelitian ini bertujuan untuk mengetahui pengaruh kualitas pelayanan secara parsial dan simultan terhadap kepuasan pelanggan. Jenis penelitian yang digunakan adalah deskriptif kuantitatif dengan sampel sebanyak 100 responden. Populasi dalam penelitian ini adalah pelanggan aktif PDAM Tirta Jeneberang IKK Borongloe di Kabupaten Gowa. Data teknik pengumpulan menggunakan teknik observasi, angket dan studi pustaka. Teknik analisis data menggunakan uji regresi linier berganda. Hasil penelitian menunjukkan bahwa berdasarkan uji parsial variabel bukti langsung, reliabilitas, daya tanggap, jaminan dan empati berpengaruh signifikan terhadap kepuasan pelanggan. pada pengujian simultan masing-masing indikator kualitas pelayanan (bukti langsung, keandalan, daya tanggap, jaminan dan empati) berpengaruh signifikan terhadap kepuasan pelanggan