A diverse array of sex determination ( SD) mechanisms, encompassing environmental to genetic, have been found to exist among vertebrates, covering a spectrum from fixed SD mechanisms (mammals) to ...functional sex change in fishes (sequential hermaphroditic fishes). A major landmark in vertebrate SD was the discovery of the SRY gene in 1990. Since that time, many attempts to clone an SRY ortholog from nonmammalian vertebrates remained unsuccessful, until 2002, when DMY/dmrt1by was discovered as the SD gene of a small fish, medaka. Surprisingly, however, DMY/dmrt1by was found in only 2 species among more than 20 species of medaka, suggesting a large diversity of SD genes among vertebrates. Considerable progress has been made over the last 3 decades, such that it is now possible to formulate reasonable paradigms of how SD and gonadal sex differentiation may work in some model vertebrate species. This review outlines our current understanding of vertebrate SD and gonadal sex differentiation, with a focus on the molecular and cellular mechanisms involved. An impressive number of genes and factors have been discovered that play important roles in testicular and ovarian differentiation. An antagonism between the male and female pathway genes exists in gonads during both sex differentiation and, surprisingly, even as adults, suggesting that, in addition to sex-changing fishes, gonochoristic vertebrates including mice maintain some degree of gonadal sexual plasticity into adulthood. Importantly, a review of various SD mechanisms among vertebrates suggests that this is the ideal biological event that can make us understand the evolutionary conundrums underlying speciation and species diversity.
Clozapine-induced constipation is a frequently overlooked side effect that can prove fatal. This study aimed to investigate the prevalence of constipation and the breakdown of laxatives, and to ...identify whether use of laxative may be predicted by demographics or baseline metabolic markers in 53 Japanese treatment-resistant schizophrenia inpatients switched to clozapine. Differences of present age, onset age and duration of illness, previous antipsychotic dose using the chlorpromazine equivalent, and 10-items of metabolic markers, including fasting plasma glucose and ratio of triglyceride to high-density lipoprotein cholesterol levels were compared between the laxative and nonlaxative user groups. Sequential changes of defecation scores using Bristol stool form scale, and clozapine dosage at 1, 2 and 3 months were evaluated within each group. Multiple linear stepwise regression analysis was performed to assess the predicting use of laxatives. Half of subjects required treatment with laxative, were significantly older and had longer durations of illness than nonlaxative users. Magnesium oxide and lubiprostone were mainly used singly or in combination. Longer disease duration, and lower levels of fasting blood glucose and insulin resistance were predicting the use of laxatives. Screening and preventive strategies for minimizing clozapine-related constipation should be established in future study.
Remarkable optical/electrical features are expected in two-dimensional group-IV monochalcogenides (MXs; M = Sn/Ge and X = S/Se) with a uniquely distorted layered structure. The lone pair electrons in ...the group-IV atoms are the origin of this structural distortion, while they also cause a strong interlayer force and high chemical reactivity. The fabrication of chemically stable few-to-monolayer MX has been a significant challenge. We have observed that, once the SnS surface is oxidized, the SnO
top layer works as a passivation layer for the SnS layer underneath. In this work, the SnO
/SnS hetero-structure is studied structurally, optically, and electrically. When tape-exfoliated bulk SnS is oxygen-annealed under a reduced pressure at 10 Pa, surface oxidation and SnS sublimation proceed simultaneously, resulting in a monolayer-thick SnS layer with the SnO
passivation layer. The field-effect transistor of nine-layer SnS prepared via mechanical exfoliation exhibits a p-type characteristic because of intrinsic Sn vacancies, whereas ambipolar behavior is observed for the monolayer-thick SnS obtained via oxygen annealing probably owing to the additional n-type doping by S vacancies. This work on monolayer-thick SnS fabrication can be applied to other unstable lone pair analogues and can facilitate future research on MXs.
Steroid hormones have been shown to play important roles in triggering sex change. However, the upstream mechanism that regulates the secretion of sex steroid hormones controlling sex change is not ...yet known. Cortisol, the primary glucocorticoid in teleost fish, is known to exhibit anti-stress action and is involved in many physiological functions, including regulation of steroidogenesis. Therefore, cortisol could be one of the candidate factors involved in the onset of sex change. In this study, we investigated the role of cortisol in sex change in the three-spot wrasse, Halichoeres trimaculatus, by prolonged administration of cortisol. Our results showed that gonads of all individuals treated with cortisol (1,000 µg/g diet) for 6 weeks contained spermatogenic germ cells. One of them exhibited matured testes with an ovarian cavity, indicating sex change. Additionally, the plasma estradiol-17β level in the cortisol treatment group was significantly lower than in the control group suggesting that cortisol plays a direct and/or indirect role in the regulation of estrogen production. These data imply that cortisol might be involved in the regulation of steroidogenesis by causing a decrease in the estrogen level, leading to the onset of sex change.
Background: In Japan, the number of pediatric cancer cases was approximately 2,200 in 2019. Notably, 15 hospitals are designated for pediatric cancer in Japan. This study focused on the outpatient ...nurses of a pediatric specialty hospital supporting these designated hospitals. The study aimed to clarify the support that these nurses provide to pediatric cancer survivors as well as their thoughts on supporting the patients at pediatric specialty hospitals. Methods: This study used qualitative inductive research methods and conducted semi-structmed free-response interviews with outpatient nurses working at a pediatric specialty hospital. Data analysis was performed using the Modified Grounded Theory Approach (M-GTA). Results: Overall, 15 outpatient nurses were included in the study. Moreover, the M-GTA analysis generated four core categories. The thought process related to a long-term follow-up outpatient clinic for pediatric cancer survivors included considering factors that posed difficulty in the establishment of such a clinic, reconsidering the importance of establishing such a clinic, and contemplating about establishing a desirable clinic. This was based on the belief of the outpatient nurses regarding building a trusting relationship with the patients. Conclusion: Owing to manpower issues, no guidance was provided for the pediatric cancer survivors at outpatient clinics, and follow-up care was provided only by physicians. Moreover, outpatient nurses recognized the problems faced by patients throughout their lives and understood the need to solve them, but they could not provide effective guidance. Because pediatric cancer survivors are at high risk of disease- and treatment-related outcomes, there is a need to develop a system that facilitates collaboration between different professional groups in order to improve their quality of life.
Background: Childhood cancers affect 2,000-2,500 individuals per year in Japan, with onset at infancy. In Japan, there are -50,000 childhood cancer survivors, and following recovery, the mother ...supports the child at home. Aim: To elucidate how mothers confront problems following the discharge of childhood cancer survivors and the provision of guidance to the child regarding self-care. Methodology: After creating an interview guide coinciding with the study objectives, semi-structured interviews of five mothers of childhood cancer survivors were conducted. The data obtained was analyzed using the modified grounded theory approach. Results: The challenges faced by mothers of childhood cancer survivors who underwent surgery as children and the self-care guidance process comprised 5 core categories and nine categories from 34 concepts. The core categories included "fonnation of beliefs to confront the disease," "promotion of understanding suitable to the child's age at onset," "individual actions against the lack of infonnation," "preparation of the enviromnent by oneself when the child needs to be monitored," and "reflection and acknowledgment of the process to date." Conclusions: The mothers of childhood cancer survivors with onset at infancy preferred for the dúld to understand their disease; however, the mothers experienced difficulty in explaining the disease owing to a lack of knowledge. To enhance their knowledge to facilitate the child's self-care, mothers joined patient groups to gather infonnation. Furthennore, following discharge, it was difficult for parents and their children to establish relationships with medical staff and no avenue was available for consultation in case of any concerns.
The Nile tilapia, a gonochoristic teleost fish with an XX/XY sex-determining system, provides an excellent model for studying gonadal sex differentiation because genetic all-females and all-males are ...available. In this study, we used quantitative real-time RT-PCR to determine the precise timing of the gonadal expression of 17 genes thought to be associated with gonadal sex differentiation in vertebrates. Gonads were isolated from all-female and all-male tilapia before (5-15 days after hatching dah) and after (25-70 dah) morphological sex differentiation. The transcript of aromatase (cyp19a1a), an enzyme responsible for producing estradiol-17beta, was expressed only in XX gonads at 5 dah, with a marked elevation in expression thereafter. In contrast, mRNA expression of steroid 11beta-hydroxylase (cyp11b2), an enzyme responsible for the synthesis of 11-ketotestosterone (11-KT, a potent androgen in fish), was found in XY gonads from 35 dah only. These results, combined with the presence of transcripts for other steroidogenic enzymes and estrogen receptors in XX gonads at 5-7 dah, are consistent with our earlier suggestion that estradiol-17beta plays a critical role in ovarian differentiation in tilapia, whereas a role for 11-KT in testicular differentiation is questionable. A close relationship between the expression of foxl2, but not nr5a1 (Ad4BP/SF-1), and that of cyp19a1a in XX gonads suggests an important role for Foxl2 in the transcriptional regulation of cyp19a1a. Dmrt1 exhibited a male-specific expression in XY gonads from 6 dah onward, suggesting an important role for Dmrt1 in testicular differentiation. Sox9 and amh (anti-Mullerian hormone) showed a testis-specific expression, being evident only in the later stages of testicular differentiation. It is concluded that the sex-specific expression of foxl2 and cyp19a1a in XX gonads and dmrt1 in XY gonads during early gonadal differentiation (5-6 dah) is critical for undifferentiated gonads to differentiate into either the ovary or testis in the Nile tilapia.
Abstract
Cumulative dose effects, which are one of the main causes of errors that occur when an implantable cardiac pacemaker (ICP) is irradiated with ionizing radiation, induce permanent failure in ...ICPs. Although flattening filter free (FFF) beams, which are often used in stereotactic radiotherapy, are known to have different characteristics from conventional (with flattening filter WFF) beams, the cumulative dose effects on ICPs with FFF beams have been under-investigated. This study investigates ICP failure induced by cumulative dose effects of FFF beams. When the ICP placed in the center of the irradiation field was irradiated with 10 MV-FFF at 24 Gy/min, the cumulative dose at which failure occurred was evaluated on the basis of the failure criteria associated with high cumulative dose as described in the American Association of Physicists in Medicine Task Group 203. The ICP failures such as a mild battery depletion at a cumulative dose of 10 Gy, pacing-output voltage change >25% at a cumulative dose of 122 Gy, and the loss of telemetry capability at cumulative dose 134 Gy were induced by cumulative dose effects. The cumulative doses by which the cumulative dose effects of FFF beams induced ICP failure were not very different from those reported in previous studies with WFF beams. Therefore, radiotherapy with FFF beams (and WFF beams) for patients with ICP requires appropriate management for minimizing the cumulative dose effects.
We encountered a case of syndrome of inappropriate antidiuretic hormone secretion (SIADH) caused by duloxetine, serotonin and norepinephrine reuptake inhibitor (SNRI). A 74-year-old woman complaining ...of severe lethargy was transferred to our emergency department. Her serum sodium level was 109 mEq/L. Plasma hypo-osmolality with urine normo-osmolality was observed, indicating SIADH. Her essential hypertension had long been treated with telmisartan, and she had just started duloxetine 20 mg/day for chronic musculoskeletal pain 4 days prior to admission. On prescribing duloxetine in the primary care setting, clinicians should be aware of the possibility of duloxetine-induced hyponatremia, particularly in combination with telmisartan.
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