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The role of salt intake in the development of hypertension is prominent, but its mechanism has not been fully elucidated. Our aim was to examine the effect of transient salt intake during the prehypertensive period in hypertensive model animals. Dahl salt-sensitive rats and spontaneously hypertensive rats were fed from 6 to 14 weeks with low-salt (0.12% NaCl), normal-salt (0.8% NaCl), high-salt (7% NaCl), or high-sodium/normal-chloride diet and returned to normal-salt diet for 3 months. Rats in the high-salt group saw elevations in blood pressure (BP) not only during the treatment period but also for the 3 months after returning to normal-salt diet. We named this phenomenon salt memory. Renal arteriolar injury was found in the high-salt group at the end of experiment. Dahl salt-sensitive rats were fed from 6 to 14 weeks with high-salt diet with angiotensin receptor blocker, vasodilator, calcium channel blocker, and calcium channel blocker+angiotensin receptor blocker and returned to normal-salt diet. Although BP was suppressed to control levels by vasodilator or calcium channel blocker, elevated renal angiotensin II and renal arteriolar injury were observed, and salt memory did not disappear because of sustained renal arteriolar injury. Calcium channel blocker+angiotensin receptor blocker suppressed renal arteriolar injury, resulting in the disappearance of salt memory. Cross-transplantation of kidneys from Dahl salt-sensitive rats on high salt to control rats caused increase of BP, whereas control kidneys caused reduction in BP of hypertensive rats, inducing the central role of the kidney. These results suggest that renal arteriolar injury through BP and renal angiotensin II elevation plays important roles in the development of salt memory for hypertension. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Hypoglycemia induces rapid secretion of counterregulatory hormones such as catecholamine, glucagon, cortisol, and GH. Insulin-induced hypoglycemia is used for evaluating GH–IGF-I and ACTH–adrenal axes in patients with pituitary disorders. The aim of this study was to determine whether the response of catecholamine secretion to hypoglycemia is disrupted in patients with pituitary adenoma. METHODS: The study population comprised 23 patients with pituitary adenoma (non-functioning adenoma or prolactinoma). An insulin tolerance test was performed and serum catecholamines as well as plasma GH and serum cortisol were measured. RESULTS: The study patients showed diminished response of plasma epinephrine to insulin-induced hypoglycemia. With the cutoff level of peak epinephrine for defining severe impairment set at 400 pg/ml, more patients with secondary adrenal insufficiency showed severe impairment of the epinephrine response than did those without it. Peak epinephrine levels to insulin-induced hypoglycemia were significantly correlated with peak cortisol levels. In patients with secondary hypothyroidism, secondary hypogonadism, GH deficiency, or diabetes insipidus, the prevalence of severe impairment of the epinephrine response was similar to that in patients without these deficiencies. CONCLUSIONS: Impaired epinephrine secretion in response to insulin-induced hypoglycemia was frequently observed in patients with pituitary adenoma. This disorder was especially severe in patients with secondary adrenal insufficiency. [ABSTRACT FROM AUTHOR]

Single-shot optical imaging based on ultrashort lasers has revealed nonrepetitive processes in subnanosecond timescales beyond the recording range of conventional high-speed cameras. However, nanosecond photography without sacrificing short exposure time and image quality is still missing because of the gap in recordable timescales between ultrafast optical imaging and high-speed electronic cameras. Here, we demonstrate nanosecond photography and ultrawide time-range high-speed photography using a spectrum circuit that produces interval-tunable pulse trains while keeping short pulse durations. We capture a shock wave propagating through a biological cell with a 1.5-ns frame interval and 44-ps exposure time while suppressing image blur. Furthermore, we observe femtosecond laser processing over multiple timescales (25-ps, 2.0-ns, and 1-ms frame intervals), showing that the plasma generated at the picosecond timescale affects subsequent shock wave formation at the nanosecond timescale. Our technique contributes to accumulating data of various fast processes for analysis and to analyzing multi-timescale phenomena as a series of physical processes. [ABSTRACT FROM AUTHOR]

Targeting PD-1/PD-L1 has shown the ability to improve overall survival in urothelial carcinoma; however, there are cases of nonresponse and resistance. In this study, we evaluated time-course changes in all tumor locations after pembrolizumab treatment to examine the differences in immune checkpoint inhibitor efficacy in different organs. We also examined the usefulness of neutrophil-to-lymphocyte ratio, CRP, and kinetics as prognostic biomarkers in urothelial carcinoma treated with pembrolizumab. Introduction: Since tumors in different human organs may have different tumor microenvironments, we evaluate timecourse changes in all tumor locations after pembrolizumab treatment in urothelial carcinoma (UC) to examine the differences in efficacy of pembrolizumab per organ. Further, we uncover the usefulness of inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR), CRP, and kinetics of these markers to predict pembrolizumab success and relation to overall survival (OS) in UC. Patients and Methods: A total of 115 cancerous lesions from 44 UC patients were measurable based on RECIST 1.1 cr iter ia. The ser um CRP and NLR levels were measured at baseline prior to pembrolizumab treatment and at least every 3 weeks just prior to pembrolizumab administration. Results: Site-specific success (ie, patients with CR/PR/SD by RESIST 1.1) rates for pembrolizumab treatments were as follows: primary tumors: 67%, lymph node: 70%, lung: 44%, liver: 40%, and peritoneal metastasis: 56%. Focusing on the major metastasis sites, lymph nodes and lungs, we examined the relationships between NLR, CRP, or that kinetics and pembrolizumab success. In lymph nodes, both early NLR kinetics (P = .005) and CRP kinetics (P = .035) was a predictor for pembrolizumab success. On the other hand, none of 4 was not in lung metastases. Regarding to the mortality, the multivariate analysis revealed that early NLR kinetics was a prognostic biomarker for OS among the 4, independent of performance status and liver metastasis. Conclusion: We revealed that site-specific pembrolizumab success in UC. Early NLR kinetics was a predictor for lymph node pembrolizumab success and OS in our cohorts. [ABSTRACT FROM AUTHOR]

The aim of this study was to validate the contemporary grading system. Our follow-up study revealed that men with Gleason score (GS) 4D5 and those with Gleason grade group 4 had a similar prognosis. However, there was a significant discrepancy in prognosis between GS 4D5 and GS 5D4 or higher. Gleason grade groups 4 and 5 in the contemporary grading system should be reviewed. Introduction: The aim of this study was to validate contemporary grading systems, in particular, the Gleason grade group (GGG) 5. Patients and Methods: We retrospectively reviewed the clinicopathologic data of 176 patients who underwent radical prostatectomy and whose pathologic results were GGG 4 or 5. The endpoints were biochemical recurrence (BCR) and castration-resistant prostate cancer (CRPC). Results: The GGG 4 group was composed of 69 patients. The GGG 5 group consisted of 78 patients with GS 4þ5 and 29 patients with GS 5þ4 or higher. The 5-year BCR-free survival rates for men with GGG 4, GS 4þ5, and GS 5þ4 or higher were 59%, 54%, and 20%, respectively, and the 5-year CRPC-free survival rates were 98%, 100%, and 88%, respectively. Both the BCR- and CRPC-free survival rates were significantly higher in GS 4þ5 than in GS 5þ4 or higher (P < .001 and P = .002, respectively), but there were no significant differences between GGG 4 and GS 4þ5 (P = .702 and P = .803, respectively). The multivariate analysis demonstrated that GS 5þ4 or higher (hazard ratio, 3.4; P = .002) and lymphovascular invasion (hazard ratio, 3.4; P < .001) greatly affected BCR. Conclusion: Our follow-up study revealed that men with GS 4þ5 and those with GGG 4 had a similar prognosis. However, there was a significant discrepancy in prognosis between GS 4þ5 and GS 5þ4 or higher. This suggested that GGG 4 and 5 in the contemporary prostate cancer grading system should be reviewed. Furthermore, lymphovascular invasion may be useful to subgroup these pathologically high-risk patients. [ABSTRACT FROM AUTHOR]