Sexuality education in Japanese medical schools

This is the first study on sexuality education in Japanese medical schools. <div><br></div

DataSheet_1_Body composition and testosterone in men: a Mendelian randomization study.docx

BackgroundTestosterone is an essential sex hormone that plays a vital role in the overall health and development of males. It is well known that obesity decreases testosterone levels, but it is difficult to determine the causal relationship between body composition and testosterone.MethodsTo investigate potential causal associations between body composition and testosterone levels by a first time application of Mendelian randomization methods. Exposure variables in men included body composition (fat mass, fat-free mass, and body mass index). In addition to whole body fat and fat-free mass, we examined fat and fat-free mass for each body part (e.g., trunk, left arm, right arm, left leg and right leg) as exposures. Instrumental variables were defined using genome-wide association study data from the UK Biobank. Outcome variables in men included testosterone levels (total testosterone [TT], bioavailable testosterone [BT], and sex hormone-binding globulin [SHBG]). A one-sample Mendelian randomization analysis of inverse-variance weighted and weighted median was performed.ResultsThe number of genetic instruments for the 13 exposure traits related to body composition ranged from 156 to 540. Genetically predicted whole body fat mass was negatively associated with TT (β=-0.24, P=5.2×10-33), BT (β=-0.18, P=5.8×10-20) and SHBG (β=-0.06, P=8.0×10-9). Genetically predicted whole body fat-free mass was negatively associated with BT (β=-0.04, P=2.1×10-4), but not with TT and SHBG, after multiple testing corrections. When comparing the causal effect on testosterone levels, there was a consistent trend that the effect of fat mass was more potent than that of fat-free mass. There were no differences between body parts.ConclusionThese results show that reducing fat mass may increase testosterone levels.</p

Table_1_Body composition and testosterone in men: a Mendelian randomization study.xlsx

BackgroundTestosterone is an essential sex hormone that plays a vital role in the overall health and development of males. It is well known that obesity decreases testosterone levels, but it is difficult to determine the causal relationship between body composition and testosterone.MethodsTo investigate potential causal associations between body composition and testosterone levels by a first time application of Mendelian randomization methods. Exposure variables in men included body composition (fat mass, fat-free mass, and body mass index). In addition to whole body fat and fat-free mass, we examined fat and fat-free mass for each body part (e.g., trunk, left arm, right arm, left leg and right leg) as exposures. Instrumental variables were defined using genome-wide association study data from the UK Biobank. Outcome variables in men included testosterone levels (total testosterone [TT], bioavailable testosterone [BT], and sex hormone-binding globulin [SHBG]). A one-sample Mendelian randomization analysis of inverse-variance weighted and weighted median was performed.ResultsThe number of genetic instruments for the 13 exposure traits related to body composition ranged from 156 to 540. Genetically predicted whole body fat mass was negatively associated with TT (β=-0.24, P=5.2×10-33), BT (β=-0.18, P=5.8×10-20) and SHBG (β=-0.06, P=8.0×10-9). Genetically predicted whole body fat-free mass was negatively associated with BT (β=-0.04, P=2.1×10-4), but not with TT and SHBG, after multiple testing corrections. When comparing the causal effect on testosterone levels, there was a consistent trend that the effect of fat mass was more potent than that of fat-free mass. There were no differences between body parts.ConclusionThese results show that reducing fat mass may increase testosterone levels.</p

Screening of mutation-restored (Pkd1(+/R+)) iPSCs from iPSCs heterozygous for <i>Pkd1</i> knockout (KO) (Pkd1(+/−)).

<p><b>a,</b> Normal colony morphology of Pkd1(+/−) iPSCs expressing fluorescence marker protein, GFP. <b>b,</b> Expression of pluripotent marker proteins, Oct4, Sox2, and Nanog in Pkd1(+/R+) iPSCs by immunohistochemical analyses. <b>c,</b> Transcription of pluripotent marker genes in Pkd1(+/−) and Pkd1(+/R+) iPSCs by RT-PCR analyses. <b>d,</b> Secondary screening of Pkd1(+/R+) iPSCs by genomic PCR analyses. <b>e,</b> Verification of replacement of the KO allele by the wild-type (WT) allele through spontaneous mitotic recombination in Pkd1(+/R+) iPSCs by Southern blot hybridization analyses. Relative intensity is noted under the 15.1 kb band. <b>f,</b> Determination of the origin of Pkd1(+/R+) iPSCs by Southern blot hybridization.</p

Frequency of spontaneous mitotic recombination at <i>Pkd1</i> KO allele in iPSCs.

<p>Frequency of spontaneous mitotic recombination at <i>Pkd1</i> KO allele in iPSCs.</p

Restoration of ADPKD phenotype in adult chimeric mice with Pkd1(+/R+) iPSCs.

<p><b>a,</b> Newborn chimeric mouse (green) generated by micro injection of Pkd1(+/−) iPSCs into host blastocyst (left panel). Contribution of Pkd1(+/R+) iPSCs into a chimeric kidney is visualized by GFP expression (right panel). <b>b,</b> Contribution of iPSCs into chimeric kidneys. Degree of iPSC contribution to each kidney collected from different chimeric mouse with Pkd1(+/−), or Pkd1(+/R+) iPSCs is indicated by a green bar. <b>c,</b> A hematoxylin-eosin (HE) section of Pkd1(+/−) chimeric kidney. A cyst was recognized as diameter greater than 200 µm (left panel). Pkd1(+/−)iPSC-derived cells (green) are located on the cyst wall (white arrow heads in right panel). Nuclei are stained as blue by DAPI. <b>d,</b> Frequency of cyst generation in kidneys from Pkd1(+/−), or Pkd1(+/R+) iPSC chimeric mice. The number of cysts was counted on HE sections of kidneys, in which degree of chimerism was estimated by GFP analysis in <b>b</b> (33 sections from each kidney). Error bars, s.e.m.</p

Scheme of in vitro screening and in vivo assay of mutation-restored Pkd1(+/R+) iPSCs.

<p>The knockout (KO) allele of <i>Pkd1</i> is spontaneously replaced with the wild-type allele through mitotic recombination occurring in rounds of cell division of Pkd1(+/−) iPSCs. Phenotype of ADPKD (autosomal dominant polycystic kidney disease) caused by the mutation of <i>Pkd1</i> is detected in kidneys from adult chimeric mice with Pkd1(+/−), but not Pkd1(+/R+), iPSCs.</p

Beneficial effect of combined treatment with octreotide and pasireotide in PCK rats, an orthologous model of human autosomal recessive polycystic kidney disease

<div><p>Increased intracellular cyclic AMP (cAMP) in renal tubular epithelia accelerates the progression of polycystic kidney disease (PKD). Thus, decreasing cAMP levels by an adenylyl cyclase inhibitory G protein activator is considered to be an effective approach in ameliorating PKD. In fact, pasireotide (PAS) was effective in reducing disease progression in animal models of PKD. However, hyperglycemia caused by the administration of PAS is an adverse effect in its clinical use. Whereas, co-administration of octreotide (OCT) with PAS did not increase serum glucose in normal rats. In the current study, we examined the efficacy of combined treatment with OCT and PAS in PCK rats, an autosomal recessive PKD model. Four-week-old PCK males were treated with the long-acting release type of OCT, PAS, or a combination of both (OCT/PAS) for 12 weeks. After termination, serum and renal tissue were used for analyses. Kidney weight, kidney weight per body weight, renal cyst area, renal Ki67 expression, and serum urea nitrogen were significantly decreased either in the PAS or OCT/PAS group, compared with vehicle. Renal tissue cAMP content was significantly decreased by PAS or OCT/PAS treatment, but not OCT, compared with vehicle. As a marker of cellular mTOR signaling activity, renal phospho-S6 kinase expression was significantly decreased by OCT/PAS treatment compared with vehicle, OCT, or PAS. Serum glucose was significantly increased by PAS administration, whereas no difference was shown between vehicle and OCT/PAS, possibly because serum glucagon was decreased either by the treatment of OCT alone or co-application of OCT/PAS. In conclusion, since serum glucose levels are increased by the use of PAS, its combination with OCT may reduce the risk of hyperglycemia associated with PAS monotherapy against PKD progression.</p></div

Effects of somatostatin analogs on representative kidney sections, serum IGF-1 levels, renal IGF-1R, and ERK activity.

<p>Representative kidney sections were stained with hematoxylin and eosin in each group (<i>n</i> = 6 per each, A). Serum insulin-like growth factor-1 (IGF-1) levels (ng/mL, B). The parameters are expressed as mean ± SD. Difference between CONT and each drug-treated group, **: <i>P</i> < 0.01. Comparison between OCT and OCT/PAS in PCK males, $: <i>P</i> < 0.05,$ $: <i>P</i> < 0.01. Comparison between PAS alone and OCT/PAS in PCK males, #: <i>P</i> < 0.05. Immunoblots were probed with an antibody to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) or IGF-1 receptor (IGF-1R) (C), and an antibody to extracellular signal-regulated kinase (ERK) or phosphorylated-ERK (pERK) (E). IGF-1R/GAPDH (D) and pERK/ERK (F) ratios were determined from density analysis of the bands. The parameters are expressed as mean ± SD. Difference between CONT and each drug-treated group, *: <i>P</i> < 0.05, **: <i>P</i> < 0.01.</p

Effects of somatostatin analogs on serum glucose, insulin, glucagon and cortisol levels.

<p>Effects of somatostatin analogs on serum glucose, insulin, glucagon and cortisol levels.</p