Long-Term Effects of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease: Predictors of Treatment Response and Safety over 6 Years of Continuous Therapy.

Tolvaptan, an oral vasopressin V2 receptor antagonist, reduces renal volume expansion and loss of renal function in patients with autosomal dominant polycystic kidney disease (ADPKD). Data for predictive factors indicating patients more likely to benefit from long-term tolvaptan are lacking. Data were retrospectively collected from 55 patients on tolvaptan for 6 years. Changes in renal function, progression of renal dysfunction (estimated glomerular filtration rate [eGFR], 1-year change in eGFR [ΔeGFR/year]), and renal volume (total kidney volume [TKV], percentage 1-year change in TKV [ΔTKV%/year]) were evaluated at 3-years pre-tolvaptan, at baseline, and at 6 years. In 76.4% of patients, ΔeGFR/year improved at 6 years. The average 6-year ΔeGFR/year (range) minus baseline ΔeGFR/year: 3.024 (-8.77-20.58 mL/min/1.73 m2). The increase in TKV was reduced for the first 3 years. A higher BMI was associated with less of an improvement in ΔeGFR (p = 0.027), and family history was associated with more of an improvement in ΔeGFR (p = 0.044). Hypernatremia was generally mild; 3 patients had moderate-to-severe hyponatremia due to prolonged, excessive water intake in response to water diuresis-a side effect of tolvaptan. Family history of ADPKD and baseline BMI were contributing factors for ΔeGFR/year improvement on tolvaptan. Hyponatremia should be monitored with long-term tolvaptan administration.

Vasoreactivity of the optic nerve head, nailfold, and facial skin in response to cold provocation in normal-tension glaucoma patients.

BACKGROUND: The dysfunction of optic nerve head (ONH) hemodynamics has been suggested to be involved in the pathogenesis of normal-tension glaucoma (NTG). The aim of this study was to compare vasoreactivity in the ONH, nailfold, and facial skin in response to cold-water provocation in NTG patients and healthy controls. METHODS: We performed cold-water provocation in 14 eyes of 14 NTG patients and 15 eyes of 15 age-matched control subjects. Laser speckle flowgraphy-derived tissue-area mean blur rate (MT), skin blood flowmetry-derived pulse wave amplitude (PA), nailfold capillaroscopy-derived nailfold capillary diameter, and other clinical parameters were recorded at baseline and 4 and 6 min after the cold stimulus. We compared changes (as percentages) in these variables in the NTG and control subjects with a linear mixed-effects model and evaluated correlations between these changes with Spearman's rank correlation coefficient. RESULTS: The interaction term between the NTG group (reference, control group) and the 4-min protocol step (reference, baseline) significantly affected the changes in MT, nailfold capillary diameter and PA (ß = -9.51%, P = 0.017, ß = -20.32%, P = 0.002; ß = + 18.06%, P = 0.017, respectively). The change in MT was positively correlated with the change in nailfold capillary diameter, and negatively correlated with the change in PA (r = 0.39, P = 0.036; r = -0.40, P = 0.031, respectively). CONCLUSION: NTG patients showed abnormal vasoconstriction in the ONH and nailfold and vasodilation in the facial skin in response to cold-water provocation.

System A amino acid transporter SNAT2 shows subtype-specific affinity for betaine and hyperosmotic inducibility in placental trophoblasts.

Betaine uptake is induced by hypertonic stress in a placental trophoblast cell line, and involvement of amino acid transport system A was proposed. Here, we aimed to identify the subtype(s) of system A that mediates hypertonicity-induced betaine uptake. Measurement of [(14)C]betaine uptake by HEK293 cells transiently transfected with human or rat sodium-coupled neutral amino acid transporters (SNATs), SNAT1, SNAT2 and SNAT4 revealed that only human and rat SNAT2 have betaine uptake activity. The Michaelis constants (Km) of betaine uptake by human and rat SNAT2 were estimated to be 5.3 mM and 4.6 mM, respectively. Betaine exclusively inhibited the uptake activity of SNAT2 among the rat system A subtypes. We found that rat SNAT1, SNAT2 and SNAT4 were expressed at the mRNA level under isotonic conditions, while expression of SNAT2 and SNAT4 was induced by hypertonicity in TR-TBT 18d-1 cells. Western blot analyses revealed that SNAT2 expression on plasma membrane of TR-TBT 18d-1 cells was more potently induced by hypertonicity than that in total cell lysate. Immunocytochemistry confirmed the induction of SNAT2 expression in TR-TBT 18d-1 cells exposed to hypertonic conditions and indicated that SNAT2 was localized on the plasma membrane in these cells. Our results indicate that SNAT2 transports betaine, and that tonicity-sensitive SNAT2 expression may be involved in regulation of betaine concentration in placental trophoblasts.

Highly chemoselective aerobic oxidation of amino alcohols into amino carbonyl compounds.

The direct oxidation of unprotected amino alcohols to their corresponding amino carbonyl compounds has often posed serious challenges in organic synthesis and has constrained chemists to adopting an indirect route, such as a protection/deprotection strategy, to attain their goal. Described herein is a highly chemoselective aerobic oxidation of unprotected amino alcohols to their amino carbonyl compounds in which 2-azaadamantane N-oxyl (AZADO)/copper catalysis is used. The catalytic system developed leads to the alcohol-selective oxidation of various unprotected amino alcohols, carrying a primary, secondary, or tertiary amino group, in good to high yield at ambient temperature with exposure to air, thus offering flexibility in the synthesis of nitrogen-containing compounds.

Prediction of low-addition segmented refractive intraocular lens position and deviation using anterior-segment optical coherence tomography.

This study aimed to develop and analyze the accuracy of predictive formulae for postoperative anterior chamber depth, tilt, and decentration of low-added-segment refractive intraocular lenses. This single-center, retrospective, observational study included the right eyes of 96 patients (mean age: 72.43 ± 6.58 years), who underwent a cataract surgery with implantation of a low-added segmented refractive intraocular lens at the Medical University Hospital between July 2019 and January 2021, and were followed up for more than 1 month postoperatively. The participants were divided into an estimation group to create a prediction formula and a validation group to verify the accuracy of the formula. Anterior segment optical coherence tomography (CASIA 2, Tomey Corporation, Japan) and swept-source optical coherence tomography biometry (IOL Master 700, Carl Zeiss Meditec AG) were used to measure the anterior ocular components. A predictive formula was devised for postoperative anterior chamber depth, intraocular lens tilt, and intraocular lens decentration (p <0.01) in the estimation group. A significant positive correlation was observed between the estimated values calculated using the prediction formula and the measured values for postoperative anterior chamber depth (r = 0.792), amount of intraocular lens tilt (r = 0.610), direction of intraocular lens tilt (r = 0.668), and amount of intraocular lens decentration (r = 0.431) (p < 0.01) in the validation group. In conclusion, our findings reveal that predicting the position of the low-added segmented refractive intraocular lens enables the prognosis of postoperative refractive values with a greater accuracy in determining the intraocular lens adaptation.

The effect of a brinzolamide/brimonidine fixed combination on optic nerve head blood flow in rabbits.

PURPOSE: The purpose of this study was to investigate the effect of a 1% brinzolamide and 0.1% brimonidine fixed combination (BBFC) on ONH blood flow (BF) in rabbits. METHODS: A crossover study was conducted on pigmented rabbits; a physiological saline solution, brinzolamide, or BBFC was administered for eight days. ONH BF, intraocular pressure (IOP) and systemic parameters were measured before the eighth day's first dose and at 6, 9, 12, and 14 hours after the dose. ONH BF was assessed using laser speckle flowgraphy, and mean blur rate (MBR) values were calculated. The percentage against baseline of each parameter was calculated, and intergroup comparisons were performed at each time point. RESULTS: There were no significant differences in the percentage change in systemic parameters. At 6 hours after administration, the BBFC group showed a significantly higher percentage change in large vessel area-MBR (%MV) compared to the control group (98.6±16.8%MV vs. 81.3±7.9%MV, P = 0.03). On the other hand, the brinzolamide group did not show a significant difference. Both the brinzolamide and BBFC groups had significantly lower percentage change in IOP (%IOP) compared to the control group (90.6±5.0%IOP, 93.3±2.9%IOP, and 99.2±1.7%IOP, respectively, P < 0.01). CONCLUSION: BBFC effectively reduces IOP and mitigates diurnal fluctuation-induced decreases in ONH BF.

Germ Cell Neoplasia in Situ Recognized Incidentally with Complaining of Discomfort in the Right Testis: A Case Report.

A 27-year-old man experienced discomfort in his right testis in early September, 2021, and visited the hospital five days later. Physical examination did not detect any abnormalities in the scrotum. However, an ultrasound revealed a tumor in the central part of the right testis, and a Magnetic Resonance Imaging (MRI) showed a tumor 2.7cm in diameter with clear boundaries and a marginally smooth surface. The level of alpha-fetoprotein, human chorionic gonadotropin, human chorionic gonadotropin-ß subunit, and lactate dehydrogenase were within normal limits. A Computed Tomography (CT) scan showed no abnormalities. We can't rule out the possibility of malignancy, right radical orchiectomy was performed with a diagnosis of right testicular tumor in mid-September 2021. The macroscopic lesion was 1.5×1.3 cm in size, and no viable tumorous cells were found pathologically. Atypical cells were observed in the seminiferous tubules from the spermatic cord, which were positively stained with immune-histochemical staining CD117 (c-kit), D2-40, and MIB-1 but negatively with alpha-fetoprotein, human chorionic gonadotropin, and human chorionic gonadotropin-ß subunit. The pathological diagnosis was germ cell neoplasia in situ, and no continuity was observed between these cells and bleeding necrosis. The patient has been followed up for 1 year and 4 months after surgery, with no recurrence or metastasis observed.

Vision With Retrodots and Factors for Declining Visual Function.

Purpose: We investigated decline in the visual function of eyes with retrodots (RDs)-a subtype of cataract. Method: This study included 57 eyes with RD opacity only (mean age 72.3 ± 5.2 years) and 34 eyes with transparent lenses (mean age 71.4 ± 3.7 years). A physician diagnosed lens opacity. Using the Kanazawa Medical University Classification and Grading System, the eyes were classified into the RD-1 (37 eyes, RDs <25% of the 3-mm pupil area) and RD-2 (20 eyes, RDs ≥25% of the 3-mm pupil area) groups. Corrected distance visual acuity, contrast visual acuity, ocular refractive power, lens power, straylight, and backward light-scattering intensity and their relationship with visual function decline and optical characteristics of the eyeball were evaluated. Results: Corrected distance visual acuity was significantly lower in the RD eyes than in controls. Contrast visual acuity decreased significantly in the RD-2 eyes in all environments and in the RD-1 eyes in the evening (EVE) and EVE + glare. Straylight was significantly higher in the RD-2 eyes than in the controls and RD-1 eyes but not different between the RD-1 eyes and controls. The RD-2 eyes were significantly more myopic than the controls and RD-1 eyes. Conclusion: When the opacity of RD eyes is ≥25%, the visual acuity and contrast visual acuity decrease and straylight increases. Furthermore, myopia occurs as the refractive power of the lens increases. Moreover, visual function decline may be due to an increase in the straylight value, which is necessary for determining surgical indications.

Association among pterygium, cataracts, and cumulative ocular ultraviolet exposure: A cross-sectional study in Han people in China and Taiwan.

PURPOSE: Pterygium is an ocular surface disorder mainly caused by ultraviolet (UV) light exposure. This study explored the relationships between six cataract types with pterygium and UV exposure. METHODS: We have previously studied cataracts in residents of three regions in China and Taiwan with different UV intensities. From that study, we identified 1,547 subjects with information on the presence or absence of pterygium. Pterygium severity was graded by corneal progress rate. Cataracts were graded by classification systems as three main types (cortical, nuclear, posterior subcapsular) and three subtypes (retrodots, waterclefts, fiber folds) with high prevalence in middle-aged and elderly people. We calculated the cumulative ocular UV exposure (COUV) based on subject data and National Aeronautics and Space Administration data on UV intensities and used logistic regression to calculate odds ratios for the associations of COUV, cataract, and pterygium. RESULTS: We found an overall pterygium prevalence of 23.3%, with significant variation among the three regions. Four cataract types (cortical, nuclear, posterior subcapsular, and retrodots) were significantly associated with the presence of pterygium. CONCLUSIONS: There was a significant association between COUV and pterygium, indicating that COUV is associated with the risk of pterygium development and that pterygium is useful as an index of UV exposure. Furthermore, the type of cataract in eyes with pterygium may indicate the level of UV exposure.

[Functions of pharmacy as medical care provider].

With the 2006 amendment of the Medical Services Law,pharmacy dispensing of prescription drug orders was specified as medical care provider. As a result of specialization in pharmacy going forward, 60% of outpatients now use community pharmacies to fill their prescriptions. Meanwhile, pharmacy has been establishing a procedural system for insurance pharmacy operation. It also is a common practice for a pharmacist to visit home care patient under the physician's direction with the patient's consent. With pharmacy's function has been changing as well as undergoing major changes in the law, a prefectural pharmacy search system was used to carry out a study of home care-based pharmacy functions. In fact, conducting a study over the month of February 2010, we used a questionnaire survey targeting 226 pharmacies in Tokyo and three other prefectures. The questionnaire return rate was 42.6%. The results of the study showed the followings; 59 pharmacies conducted home visits, 59 pharmacies accepted payments covered by insurance, and 24 pharmacies participated with patients in joint discharge guidance. It is clear that pharmacy has broadened their functions from a filling of outpatient prescriptions to home based healthcare services.

Carotid artery intima-media thickness, HDL cholesterol levels, and gender associated with poor visual acuity in patients with branch retinal artery occlusion.

PURPOSE: To investigate factors associated with poor visual acuity (VA) in branch retinal artery occlusion (BRAO). METHODS: This was a retrospective cross-sectional study of 72 eyes with BRAO of 72 patients. For statistical comparison, we divided the patients into worse-VA (decimal VA < 0.5) and better-VA (decimal VA > = 0.5) groups. We examined the association of clinical findings, including blood biochemical test data and carotid artery ultrasound parameters, with poor VA. RESULTS: Median age, hematocrit, hemoglobin and high-density lipoprotein (HDL) differed significantly between the groups (P = 0.018, P < 0.01, P < 0.01, and P = 0.025). There was a tendency towards higher median IMT-Bmax in the worse-VA group (worse-VA vs. better-VA: 2.70 mm vs. 1.60 mm, P = 0.152). Spearman's rank correlation test revealed that logMAR VA was significantly correlated to IMT-Bmax (rs = 0.31, P < 0.01) and IMT-Cmax (rs = 0.24, P = 0.035). Furthermore, logMAR VA was significantly correlated to HDL level (rs = -0.33, P < 0.01). Multivariate logistic regression analysis revealed that IMT-Bmax (odds ratio [OR] = 2.70, P = 0.049), HDL level (OR = 0.91, P = 0.032), and female gender (OR = 15.63, P = 0.032) were independently associated with worse VA in BRAO. CONCLUSIONS: We found that increased IMT-Bmax, decreased HDL, and female sex were associated with poor VA in BRAO patients. Our findings might suggest novel risk factors for visual dysfunction in BRAO and may provide new insights into the pathomechanisms underlying BRAO.

[The significance of visiting by pharmacist to home care patient].

The pharmacist visits the patient undergoing treatment in a house as a result that separation of pharmacy and clinic progressed and performs pharmaceutical management guidance. Because home care patients are old, and there are many kinds of the medicine to take, the pharmacist confirms the taking medicine actual situation of the patients and promotes risk management of the drug therapy. The pharmacist makes a reporting book aimed for proper use of the medicine about a visit result and donates it in the chief physician and the other medics. Most studies have not focused on reporting book. So I categorized the medicine of the patient and problems about the medical treatment.

Association between ultraviolet radiation exposure dose and cataract in Han people living in China and Taiwan: A cross-sectional study.

PURPOSE: We investigated associations between ocular ultraviolet (UV) radiation exposure dose and cataract opacities among Han people living in China and Taiwan, to assess the effects of UV exposure intensity. METHODS: This cross-sectional study included Han people aged ≥40 years (1,801 individuals, 450 in Sanya, 636 in Taiyuan, and 715 in Taichung) as subjects who completed a questionnaire including items about diabetes, smoking, steroid use, work history, and time spent outdoors, and underwent an ophthalmic examination. Right eye axial length was measured using A-mode ultrasonography or IOLMaster. Slit-lamp imaging under maximum mydriasis was used to classify cataracts into three major types [cortical (COR), nuclear (NUC), and posterior subcapsular cataracts (PSC)] and two subtypes [retrodots (RD) and waterclefts (WC)] by one ophthalmologist. COR was divided into opacity presence (CEN+) or absence (CEN-) in the central 3-mm diameter area of the pupil. COR was also subdivided into three groups according to opacity shape: axle-shaped opacity concomitant with WC, wedge-shaped opacity around the pupil to the eye center, and ring-shaped opacity in the lens equator along the pupillary margin. The cumulative ocular UV exposure (COUV) was calculated. A logistic regression analysis was used for multivariate analysis. RESULTS: Cataract odds ratios in high COUV eyes were 5.35 for NUC, 1.87 for PSC, and 1.35 for RD. In eyes with WC, risk of COR ring-shaped opacity significantly increased but that of wedge-shaped opacity (CEN+) significantly decreased. In eyes without WC, risk of COR axle-shaped opacity (CEN-) and ring-shaped opacity significantly increased but that of wedge-shaped opacity (CEN+) significantly decreased. CONCLUSIONS: Increased COUV level among Han people may be a risk factor for the development of nuclear cataracts, PSC, retrodots and ring-shaped cortical cataract. Risk of ocular UV exposure for cortical cataract may differ by opacity shape.

Correction: Association between ultraviolet radiation exposure dose and cataract in Han people living in China and Taiwan: A cross-sectional study.

[This corrects the article DOI: 10.1371/journal.pone.0215338.].

Novel propeptin analog, propeptin-2, missing two amino acid residues from the propeptin C-terminus loses antibiotic potency.

A novel inhibitor of prolyl endopeptidase, the propeptin analog propeptin-2 (C105H130N24O(24)), missing two amino acid residues from the propeptin C-terminus was isolated from the fermentation broth of propeptin-producing Microbispora sp. SNA-115 grown using a large inoculum. It shows the same enzyme inhibition activity as propeptin against prolyl endopeptidase (Ki=1.5 microM), but its antimicrobial activity against Mycobacterium phlei is more than 100-fold lower.

Age- and sex-dependency of the association between systemic antioxidant potential and glaucomatous damage.

Systemic oxidative stress is thought to be an important factor in the pathogenesis of glaucoma. In particular, low systemic antioxidative capacity, which normally counters oxidative stress, may contribute to glaucoma. Thus, we investigated the association between biological antioxidant potential (BAP), a biomarker of systemic antioxidative capacity, and glaucoma severity in patients with open-angle glaucoma (OAG). This study included 480 eyes of 240 patients with OAG and 66 healthy control eyes. We measured the BAP serum level with a free radical analyzer and compared it with a weighted estimate of the number of retinal ganglion cells (wrgc), derived from circumpapillary retinal nerve fiber layer thickness and visual field mean deviation. We found that wrgc was uncorrelated with BAP in the overall, male, and female OAG patients, but was correlated in young (aged ≤ 65 years) male OAG patients (better eye: r = 0.33, P = 0.02; worse eye: r = 0.27, P = 0.047). Furthermore, a mixed-effects regression analysis revealed that BAP was an independent contributing factor to wrgc in young male OAG patients (P = 0.02). Thus, systemic antioxidant capacity was associated with glaucomatous damage in relatively young male patients, suggesting that anti-oxidant therapy might be more effective in these patients.

Intraocular pressure decreases after muscle union surgery for highly myopic strabismus.

PURPOSE: To analyze the relationship between changes in the intraocular pressure (IOP) and dislocation angle in highly myopic strabismus patients who had undergone muscle union surgery. METHODS: Medical data were examined of eight eyes of seven consecutive patients with highly myopic strabismus, who had some limitation in abduction, received muscle union surgery and undergone pre- and postoperative IOP evaluation with a noncontact tonometer, and were retrospectively reviewed. In addition, 15 eyes of 15 patients with comitant horizontal strabismus who underwent unilateral recess-resect procedure as well as pre- and postoperative IOP evaluation were also included. The correlation between IOP changes after strabismus surgery and the dislocation angle of the globe was analyzed. RESULTS: The IOP was significantly reduced in the highly myopic strabismus group (-5.6 mmHg) but not in the fellow eye or in comitant horizontal strabismus patients. The decrease in IOP after surgery was significantly correlated with the preoperative dislocation angle of the globe (r = -0.725, p = 0.042). CONCLUSIONS: IOP is often higher in highly myopic strabismus patients than perceived, and it may indicate abnormal anatomy of the orbit rather than glaucoma. In that case, muscle union surgery can improve eye position and normalizes the IOP.

International photographic classification and grading system for myopic maculopathy.

PURPOSE: To develop a classification and grading system for myopic maculopathy. DESIGN: Development and evaluation of a classification system for myopic maculopathy based on observational case series. METHODS: A comprehensive set of myopic macular lesions was defined via literature review and through consensus meetings among retinal specialists and clinician scientists. A classification of myopic maculopathy was formulated based on fundus photographs and a modified Delphi process and consensus. Inter- and intraobserver reproducibility, assessed as agreement (%) and weighted kappa values, were evaluated. One hundred retinal photographs with myopia and myopic macular lesions were selected from case series at the High Myopia Clinic of the Tokyo Medical and Dental University, Tokyo, Japan. RESULTS: We defined 5 categories of myopic maculopathy including "no myopic retinal degenerative lesion" (Category 0), "tessellated fundus" (Category 1), "diffuse chorioretinal atrophy" (Category 2), "patchy chorioretinal atrophy" (Category 3), and "macular atrophy" (Category 4). Three additional features to supplement these categories were defined as "plus" lesions, namely, lacquer cracks, myopic choroidal neovascularization, and Fuchs spot. Posterior staphyloma was considered as a further, important sign of myopic retinopathy. The intraobserver agreement was ≥85% and the corresponding weighted kappa statistic was ≥0.6 between observations. After a brief training session, interobserver kappa statistics reached the predefined satisfactory level (≥0.4), considered as above moderate agreement. CONCLUSIONS: We propose a classification system for myopic maculopathy that was found to be reproducible. Applying a uniform classification in different studies will facilitate communication and comparison of findings from clinical trials and epidemiologic studies.