Action of manganese on puberty

Manganese (Mn) is considered important for normal growth and reproduction. Because Mn can cross the blood brain barrier and accumulate in the hypothalamus, and because it has been suggested that infants and children are potentially more sensitive to Mn than adults, we wanted to determine the effects of Mn exposure on puberty-related hormones and the onset of puberty, and discern the site and mechanism of Mn action. We demonstrated that the central administration of manganese chloride (MnCl2) stimulated luteinizing hormone (LH) release in prepubertal rats. Incubation of medial basal hypothalamus (MBH) in vitro showed this effect was due to a Mn-induced stimulation of luteinizing hormone releasing hormone (LHRH). Further demonstration that this is a hypothalamic site of action was shown by in vivo blockade of LHRH receptors and the lack of a direct pituitary action of Mn to stimulate LH release in vitro. Chronic supplementation of low dose of MnCl2 caused elevated serum levels of LH, follicle stimulating hormone (FSH) and estradiol or testosterone. Importantly, Mn supplementation advanced the timing of puberty in both sexes. We investigated the mechanism by which Mn induces LHRH/LH release from the hypothalamus. Blocking the NMDA receptor, IGF1 receptor, or inhibiting nitric oxide synthase in vivo was ineffective in altering Mn-induced LH release. Dose-response, pharmacological blockade and nitrite assessments indicated that the lowest doses of Mn used stimulated LHRH release, but did not induce nitric oxide (NO) production, while only the highest dose of Mn stimulated NO. Conversely, a dose-dependent inhibition of Mn-induced LHRH release was observed in the presence of ODQ, a specific blocker of soluble guanylyl cyclase. Furthermore, Mn stimulated the release of cyclic GMP (cGMP) and LHRH from the same MBH, and a protein kinase G (PKG) inhibitor, KT5823, blocked Mn-induced LHRH release. Collectively, these data demonstrate that Mn can stimulate specific puberty-related hormones both acutely and chronically, and furthermore, suggest that low levels of Mn facilitate the normal onset of puberty. The principal action of Mn within the hypothalamus is to facilitate the activation of guanylyl cyclase, which subsequently stimulates the cGMP/PKG pathway resulting in the stimulation of prepubertal LHRH secretion

In Vitro Chemosensitivity Using the Histoculture Drug Response Assay in Human Epithelial Ovarian Cancer

The choice of chemotherapeutic drugs to treat patients with epithelial ovarian cancer has not depended on individual patient characteristics. We have investigated the correlation between in vitro chemosensitivity, as determined by the histoculture drug response assay (HDRA), and clinical responses in epithelial ovarian cancer. Fresh tissue samples were obtained from 79 patients with epithelial ovarian cancer. The sensitivity of these samples to 11 chemotherapeutic agents was tested using the HDRA method according to established methods, and we analyzed the results retrospectively. HDRA showed that they were more chemosensitive to carboplatin, topotecan and belotecan, with inhibition rates of 49.2%, 44.7%, and 39.7%, respectively, than to cisplatin, the traditional drug of choice in epithelial ovarian cancer. Among the 37 patients with FIGO stage Ⅲ/Ⅳ serous adenocarcinoma who were receiving carboplatin combined with paclitaxel, those with carboplatin-sensitive samples on HDRA had a significantly longer median disease-free interval than patients with carboplatin- resistant samples (23.2 vs. 13.8 months, p＜0.05), but median overall survival did not differ significantly (60.4 vs. 37.3 months, p＝0.621). In conclusion, this study indicates that HDRA could provide useful information for designing individual treatment strategies in patients with epithelial ovarian cancer

A Statistical Verification Method of Random Permutations for Hiding Countermeasure Against Side-Channel Attacks

As NIST is putting the final touches on the standardization of PQC (Post Quantum Cryptography) public key algorithms, it is a racing certainty that peskier cryptographic attacks undeterred by those new PQC algorithms will surface. Such a trend in turn will prompt more follow-up studies of attacks and countermeasures. As things stand, from the attackers' perspective, one viable form of attack that can be implemented thereupon is the so-called "side-channel attack". Two best-known countermeasures heralded to be durable against side-channel attacks are: "masking" and "hiding". In that dichotomous picture, of particular note are successful single-trace attacks on some of the NIST's PQC then-candidates, which worked to the detriment of the former: "masking". In this paper, we cast an eye over the latter: "hiding". Hiding proves to be durable against both side-channel attacks and another equally robust type of attacks called "fault injection attacks", and hence is deemed an auspicious countermeasure to be implemented. Mathematically, the hiding method is fundamentally based on random permutations. There has been a cornucopia of studies on generating random permutations. However, those are not tied to implementation of the hiding method. In this paper, we propose a reliable and efficient verification of permutation implementation, through employing Fisher-Yates' shuffling method. We introduce the concept of an n-th order permutation and explain how it can be used to verify that our implementation is more efficient than its previous-gen counterparts for hiding countermeasures.Comment: 29 pages, 6 figure

Fully Parallel, One-Cycle Random Shuffling for Efficient Countermeasure in Post-Quantum Cryptography

Hiding countermeasures are the most widely utilized techniques for thwarting side-channel attacks, and their significance has been further emphasized with the advent of Post Quantum Cryptography (PQC) algorithms, owing to the extensive use of vector operations. Commonly, the Fisher-Yates algorithm is adopted in hiding countermeasures with permuted operation for its security and efficiency in implementation, yet the inherently sequential nature of the algorithm imposes limitations on hardware acceleration. In this work, we propose a novel method named Addition Round Rotation ARR, which can introduce a time-area trade-off with block-based permutation. Our findings indicate that this approach can achieve a permutation complexity level commensurate with or exceeding $2^{128}$ in a single clock cycle while maintaining substantial resistance against second-order analysis. To substantiate the security of our proposed method, we introduce a new validation technique --Identity Verification. This technique allows theoretical validation of the proposed algorithm\u27s security and is consistent with the experimental results. Finally, we introduce an actual hardware design and provide the implementation results on Application-Specific Integrated Circuit (ASIC). The measured performance demonstrates that our proposal fully supports the practical applicability

Comparative outcomes of the pathogen in cultured Jones tubes used in lacrimal bypass surgery according to follow up periods

AIM: To evaluate the pathogens in cultured Jones tubes used in lacrimal bypass surgery according to the postoperative periods and to obtain data for the prevention of infection of functional lacrimal stent invention. METHODS: Totally 71 patients (81 eyes) who underwent the removal of Jones tubes were enrolled in study. All the removed Jones tubes were cultured for bacterial and fungal identification and tested for bacterial antibiotic sensitivity. The results were analyzed according to the duration of the inserted Jones tube after lacrimal bypass surgery. RESULTS: Of the 81 eyes, bacteria were isolated from 69 eyes (85.2%) and fungi from 6 eyes (7.4%). Among 69 eyes, 40.6% showed Staphylococcus aureus (S. aureus), 11.6% were Pseudomonas aeruginosa (P. aeruginosa). Gram-positive bacteria were isolated more than Gram-negative bacteria, but Gram-negative bacteria showed a higher incidence in the Jones tube implanted for over 10y (P=0.035). The antibiotic sensitivity test showed that 46.4% of S. aureus were resistant to oxacillin. In terms of antibiotics commonly used in ocular clinical practice, vancomycin was sensitive to S. aureus and Streptococcus pneumoniae (S. pneumoniae), amikacin responded to P. aeruginosa and Proteus mirabilis (P. mirabilis). Trimethoprim/sulfamethoxazole (TMP/SMX) was all sensitive to S. aureus, S. pneumoniae and P. mirabilis except P. aeruginosa. CONCLUSION: S. aureus is the most commonly found organism in the Jones tube after lacrimal bypass surgery, and 46.4% of them are methicillin-resistant S. aureus (MRSA), sensitive to vancomycin. Especially, P. mirabilis responded with amikacin is dominantly detected in the Jones tubes implanted for more than 10y

Decreased Angiotensin II -Stimulated Aldosterone Production, but Normal Inositol Phosphate Response in Adrenal Glomerulosa Cells from Streptozotocin-Induced Diabetic Rats: Role of lnsulin

Streptozotocin(SlZ)-induced diabetic rats develop hyporeninemic hypoaldosteronism during the progression of diabetes mellitus. However,the nature and mechanism of aldosterone deficiency in diabetic rats still remain unclear and acute effects of insulin on aldosterone production in-vitro are not known. We evaluated the responses of aldosterone production to angiotensin 11 (AlI), potassium (K+), AClH and insulin in adrenal glomerulosa cells prepared from SlZ-induced diabetic rats with and without insulin treatment 2 weeks after diabetes induction. We also measured inositol phosphate<IP) levels in All-stimulated glomerulosa cells labeled with [3HI myoinositol using standardized anion exchange chromatography. Plasma renin activity and aldosterone level were not different among control rats,untreated and insulin-treated diabetic rats. Basal aldosterone production was similar in cells from the three groups. Cells from untreated diabetic rats showed a significant decrease in the maximal All (to-8M)-stimuiated aldosterone production and a tendency to be low in the maximal K+(8.7 mM)-stimulated aldosterone production, compared with control rats (3.2±2.2 \IS 7.7±2.4, P (0.05 and 4.8±1.8 \IS 8.0±3.2 ng/105 cells/hr, 0.05 (P (0.1, respectively). In contrast, there were no differences in All- and K+-stimulated aldosterone production between control and insulin-treated diabetic rats. AClH (to-8M), however, caused a similar effect on aldosterone production and insulin (I mU /ml for 1 hour) did not alter either basal or agonists-stimulated aldosterone production in cells from the three groups. All (to-8M)-induced IP formation among the three groups was similar and did not change with the addition of insulin u mU / ml), These results indicate that reduced response to All in the early phase of SlZ-induced diabetes in rats may be due to the zona glomerulosa dysfunction secondary to chronic lack of insulin and the main defect responsible for altered All effects may be located at some step(s) mediating All action downstream from IP formation

An Investigation of Lateral Geniculate Nucleus Volume in Patients With Primary Open-Angle Glaucoma Using 7 Tesla Magnetic Resonance Imaging

PURPOSE. To investigate lateral geniculate nucleus (LGN) volume of primary open-angle glaucoma (POAG) patients compared with age-and sex-matched controls using ultra-high field 7.0-T magnetic resonance imaging (MRI). METHODS. The study included 18 patients with POAG and 18 age-and sex-matched healthy volunteers. All subjects underwent imaging on a high-resolution 7.0-T MRI system. Bilateral LGNs were identified and manually delineated, and LGN volumes were compared. Peripapillary retinal nerve fiber layer (pRNFL) thickness, optic nerve head parameters (including optic disc size, rim area, and cup-to-disc ratio), and combined thickness of the ganglion cell layer and inner plexus layer (GC-IPL) were measured by Cirrus high-definition optical coherence tomography (OCT). Correlations between OCT parameters and LGN volume were investigated. RESULTS. CONCLUSIONS. On high-resolution 7.0-T MRI, LGN volumes in POAG patients are significantly smaller than those of healthy subjects. Furthermore, in patients, LGN volume was found to be significantly correlated with GC-IPL thickness of the contralateral eye. Keywords: glaucoma, lateral geniculate nucleus, retinal nerve fiber layer thickness, ganglion cell layer, inner plexiform layer, GC-IPL, optical coherence tomography, 7 tesla magnetic resonance imaging R etinal ganglion cell (RGC) degeneration is the major pathogenetic characteristic of glaucoma. 1-18 Most RGCs synapse the next neurons in the lateral geniculate nucleus (LGN), which serves as an important relay station to visual cortex