The Impact of Japan's 2004 Postgraduate Training Program on Intra-Prefectural Distribution of Pediatricians in Japan

Objective: Inequity in physician distribution poses a challenge to many health systems. In Japan, a new postgraduate training program for all new medical graduates was introduced in 2004, and researchers have argued that this program has increased inequalities in physician distribution. We examined the trends in the geographic distribution of pediatricians as well as all physicians from 1996 to 2010 to identify the impact of the launch of the new training program. Methods: The Gini coefficient was calculated using municipalities as the study unit within each prefecture to assess whether there were significant changes in the intra-prefectural distribution of all physicians and pediatricians before and after the launch of the new training program. The effect of the new program was quantified by estimating the difference in the slope in the time trend of the Gini coefficients before and after 2004 using a linear change-point regression design. We categorized 47 prefectures in Japan into two groups: 1) predominantly urban and 2) others by the definition from OECD to conduct stratified analyses by urban-rural status. Results: The trends in physician distribution worsened after 2004 for all physicians (p value<.0001) and pediatricians (p value = 0.0057). For all physicians, the trends worsened after 2004 both in predominantly urban prefectures (p value = 0.0012) and others (p value<0.0001), whereas, for pediatricians, the distribution worsened in others (p value = 0.0343), but not in predominantly urban prefectures (p value = 0.0584). Conclusion: The intra-prefectural distribution of physicians worsened after the launch of the new training program, which may reflect the impact of the new postgraduate program. In pediatrics, changes in the Gini trend differed significantly before and after the launch of the new training program in others, but not in predominantly urban prefectures. Further observation is needed to explore how this difference in trends affects the health status of the child population

Ultrastructural and Immunohistochemical Studies on Uptake and Distribution of FITC-Conjugated PLGA Nanoparticles Administered Intratracheally in Rats

Polylactide-glycolide (PLGA) nanoparticles have been developed as pulmonary drug delivery carriers. To investigate their behavior, small- (d50 = 74 nm) and large-sized (d50 = 250 nm) FITC-conjugated PLGA nanoparticles were intratracheally administered to rats and were traced for 5, 30 and 60 minutes and 24 hours after administration (HAT). Immunohistochemically, a, FITC-positive reaction was observed in type-I alveolar epithelial cells (type-I AEC), endothelial cells and alveolar macrophages in the lungs from 5 minutes after treatment (MAT) to 24 HAT in both nanoparticle groups. In the kidneys, a positive reaction was observed in proximal tubular epithelial cells at 30 MAT; the reaction peaked at 60 MAT and was reduced at 24 HAT, while no positive reaction was seen in other sites. Ultrascructurally, the number of membrane-bound vesicles, which were approximately 70 nm in size and hard to distinguish from pinocytic vesicles, apparently increased in type-I AEC and endothelial cells at 5 MAT in the small-sized group, in comparison with the control group receiving physiological saline. The number of vesicles in the large-sized group was almost same as that in the control group. On the other hand, in both nanoparticle groups, lysosomes filled with nanoparticles appeared in alveolar macrophages from 30 MAT to 24 HAT. These results indicate that PLGA nanoparticles might be quickly transferred from the alveolar space to the blood vessel via type-I alveolar epithelial cells and excreted into urine, and that there is a threshold for particle size, less than approximately 70 nm in diameter, with regard to absorption through the alveolar wall

生後早期の心理的ストレスが雌雄ラットの性成熟、性行動に与える影響

Purpose: We studied the influence of psychological stress during the early neonatal period on sexual maturation and sexual behavior in rats. Methods: Neonatal male and female rats were divided into control (C) and maternal separation (MS) groups (n = 20‐24 per group). The pups in the MS groups were placed in isolation cages for 240 minutes/d from postnatal days 2‐11. Vaginal opening (VO) in females and preputial separation (PS) in males (indicators of sexual maturation) were monitored, as was the estrous cycle in females. Thereafter, sexual behavior was monitored twice at 13 and 15 weeks of age. Results: As for sexual maturation, the onset of PS occurred significantly earlier in the MS group than in the C group, whereas the onset of VO did not differ between the groups. The length of the estrous cycle did not differ between the groups. The frequencies of sexual behaviors did not differ between the groups in either sex. Conclusions: In conclusion, early‐life psychological stress induced by MS advanced sexual maturation in male rats, whereas it did not affect sexual maturation in female rats. On the other hand, early‐life psychological stress might not affect sexual behavior in adulthood in either sex

C1B domain peptide of protein kinase Cγ significantly suppresses growth of human colon cancer cells in vitro and in an in vivo mouse xenograft model through induction of cell cycle arrest and apoptosis

Two peptides derived from the C1B domain of protein kinase Cγ (PKCγ) were shown to associate with classical PKC isozymes and modulate their activities. These C1B peptides are designated C1B1 (amino acid residues 101-112) and C1B5 (residues 141-151). Since PKC enzyme activity is shown to be involved in colon cancer development, the effect of C1B peptides on the growth of various human colon cancer cell lines was examined in vitro and in vivo. Sub-micromolar to micromolar levels of both C1B peptides induced approximately 60-70% growth attenuation in multiple colon cancer cell lines in a soft agar tumor colony assay; however, C1B5 peptide was not cytotoxic to normal colon epithelial cells in two dimensional culture. The effect of C1B5 peptide on colony growth of COLO205 cells was reversed by treatment with the PKCα/β inhibitor, Ro-32-0432. C1B peptide treatment attenuated COLO205 cells via two mechanisms: 1) cell cycle arrest and 2) stimulation of apoptosis. This is evident in G[subscript 2] arrest and increases in levels of cleaved caspase 3 and p53 phosphorylated at serine 20. Intratumoral injection of C1B5 peptide (20 mg/kg/day, every three days) markedly attenuated the growth of subcutaneous xenografts of COLO205 cells in SCID mice by 76% compared to the control. Taken together, these results strongly suggest that C1B peptides have negligible effects on normal tissues but are potentially effective chemotherapeutic agents for colon cancer

Distribution and Sequence of Pyknotic Cells in Rat Fetuses Exposed to Busulfan

Busulfan, an antineoplastic bifunctional-alkylating agent, is known to induce developmental anomalies. In the present study, we examined the distribution and sequence of pyknotic cells in rat fetal tissues exposed to busulfan. Pregnant rats on gestation day 13 were administered intraperitoneally 30 mg/kg of busulfan, and fetal tissues were examined at 6, 12, 24, 36, 48, 72 and 96 hours after treatment (HAT). Pyknosis of component cells was observed markedly in the brain, moderately in the eyes and spinal cord and mildly in the craniofacial tissue, mandible, limb buds, tail bud, ganglions, alimentary tract, lungs, kidneys, pancreas and liver. In the brain, mitotic inhibition was also detected. Most of the pyknotic cells were considered to be apoptotic cells judging from the results of TUNEL staining and electron microscopic examination. Commonly in the above-mentioned tissues, pyknotic cells began to increase at 24 HAT, peaked at 36 or 48 HAT and disappeared at 96 HAT, which is when the histological picture returned to normal in most tissues except for the brain, spinal cord and eyes. The present study clarified the outline of busulfan-induced apoptosis in rat fetuses

cDNA cloning and sequencing of component C5 of proteasomes from rat hepatoma cells

AbstractProteasomes are multicatalytic proteinase complexes consisting of a set of non-identical polypeptide subunits. A cDNA for component C5 of rat proteasomes was isolated by screening a Reuber H4TG hepatoma cell cDNA library using synthetic oligodeoxynucleotide probes corresponding to partial amino acid sequences of the protein. The polypeptide deduced from the open reading frame consisted of 240 amino acid residues with a calculated molecular weight of 26479. Computer analysis revealed little similarity of C5 to other proteins reported so far. The primary structure of C5 showed partial sequence homology to that of another component C3, but no regions of homology with the sequence of component C2. Thus C5 is concluded to be a new type of subunit of the proteasome complex

A novel PCOS rat model and an evaluation of its reproductive, metabolic, and behavioral phenotypes

Background: Although animal models of PCOS have been used in many studies, none of them can reproduce both the reproductive and metabolic phenotypes of PCOS. In addition, behavioral parameters have not been evaluated in PCOS animal models. Purpose: We tried to produce an improved rat model of PCOS, and the reproductive, metabolic, and behavioral phenotypes of the model rats were evaluated. Methods: Female rats were implanted with silicon tubes containing oil-dissolved dihydrotestosterone (Oil-DHT) as a new PCOS model. Their phenotypes were compared with those of conventional PCOS model rats (DHT), into which tubes containing crystalline DHT were implanted, and non-DHT-treated rats (control). Results: Both the Oil-DHT and DHT rats showed greater body weight gain, food intake, and fat depot weight than the control rats. Furthermore, these groups showed fewer estrous stages and increased numbers of cystic follicles. The DHT rats exhibited lower ovarian and uterine weights than the control rats, whereas no such changes were observed in the Oil-DHT rats. The Oil-DHT and DHT rats showed less locomotor activity in the light phase than the control rats. Conclusions: Our proposed PCOS model reproduced both the reproductive and metabolic phenotypes of PCOS and may have potential for PCOS research

Diaper-zero program in nursing home

With an aging population, the number of older adults admitted to nursing homes has increased. Diapers are often used to manage nursing home resident urinary incontinence, yet only one-third of these required assistance from caregivers to urinate. Unnecessary diaper use was reported in 23.9% of people, mostly for precautionary purposes. In this study, the Diaper-zero program caregivers asked residents regularly (every 2-3 h) whether they required voiding and prompted them to void. Over 11 months, the effects on 38 nursing home residents’ diaper use, nursing care level, physical activity, daily energy, and water intake were measured. A higher rate of diaper wearing was initially observed with lower daily energy and water intakes at the beginning of the Diaper-zero program, but this association was not observed after 11 months of the program. The diaper usage rate decreased significantly from 71.1% to 47.4% after 11 months. During this period, for all subjects, nursing care level, physical activity, and total daily intakes of energy and water were unchanged. In conclusion, this program enhances the desire to void, minimizing diaper usage, thus protecting the human dignity of nursing home residents

Biotin levels in blood and follicular fluid

It has been shown that biotin, a water-soluble vitamin (B7), plays roles in reproductive functions, such as oocyte maturation and embryo development, in experimental animals. On the other hand, little is known about the clinical effects of biotin on human reproduction. In this study, serum and follicular fluid biotin levels were measured in patients who underwent in vitro fertilization / intracytoplasmic sperm injection (IVF / ICSI), and their associations with reproductive outcomes were evaluated. As a result, biotin was detected in follicular fluid, as well as serum, and the biotin levels of follicular fluid were found to be positively correlated with those of serum. The biotin levels of serum were higher than those of follicular fluid, suggesting that biotin may be taken up into the follicular fluid from the blood. Although serum and follicular fluid biotin levels tended to be higher in pregnant patients than in non-pregnant patients, these data did not show the significant statistical difference. These findings indicate that biotin does not contribute to the maintenance of oocyte quality, and hence, it does not increase fertilization and pregnancy rates