Attitude and experience of obstetricians and gynecologists toward eating disorders assessment and management in Japan: A nationwide survey.

AIM: To investigate the attitudes and experiences of obstetricians and gynecologists in treating women with eating disorders (EDs) in Japan. METHODS: Members of the Japan Society of Obstetrics and Gynecology were invited to participate in a web-based survey from March 1 to 31, 2022. We asked about the attitudes of obstetricians and gynecologists toward women with weight loss-related amenorrhea and their experiences in treating EDs. We also assessed the characteristics of physicians who see many ED patients. RESULTS: A total of 662 ob/gyns. responded to the survey. While treating weight loss-related amenorrhea, 25.8% reported screening patients for EDs. 88.5% of respondents reported having treated ED patients. The main medical concerns described when treating pregnant women with ED were fetal growth restriction and preterm delivery. The most common type of ED encountered by participants in both perinatal and infertility care settings was anorexia nervosa. Characteristics of physicians who treated 10 or more EDs per year were being board certified in women's health care and not providing delivery services (OR = 4.809, 1.896). The most common comment regarding optimizing the management of patients with EDs in obstetrics and gynecology practice was the need to implement guidelines for ED management. CONCLUSIONS: Many obstetricians and gynecologists in Japan treat patients with ED. Standardized guidelines for the management of EDs for obstetricians and gynecologists are needed.

Mental health and quality of life in patients with premenstrual exacerbation: a cross-sectional study in Japan.

BACKGROUND: In the classification of premenstrual disorders (PMDs), premenstrual exacerbation (PME) is listed as one of the variants of PMDs, along with core PMD. However, the incidence of PME and its impact on mental health and quality of life have not been investigated. Therefore, we investigated the proportion of PME among women seeking treatment for premenstrual symptoms in Japan and compared the levels of anxiety, depression and quality of life between women with PME and those with core PMD. METHODS: Women who presented to the Department of Obstetrics and Gynaecology of a single institute for treatment of premenstrual symptoms and were diagnosed with PMDs using patient diaries were included in the study. Based on the diagnosis, patients were divided into two groups (core PMD and PME) and their responses to a questionnaire on mental health and quality of life at the first visit were analysed. RESULTS: A total of 32 women were diagnosed with PMDs (22 with core PMD and 10 with PME). All underlying medical conditions in women with PME were psychiatric disorders. There were no significant differences in various factors between the two groups. In terms of mental health, the PME group had higher levels of anxiety and depression than the core PMD group. Regarding quality of life, the PME group had lower scores than the core PMD group in all domains except physical and social functioning. CONCLUSIONS: Patients seeking treatment for premenstrual symptoms included many PME. Women with PME were more anxious and depressed than those with core PMD, and their quality of life was low in both physical and psychological domains. Patients with PME should be diagnosed and treated more appropriately.

Premenstrual exacerbation of underlying medical conditions is one of the variants of premenstrual disorders. This study aimed to assess the proportion of premenstrual exacerbation among patients attending a gynaecological clinic for premenstrual symptoms and to evaluate their mental health and quality of life. Women diagnosed with premenstrual disorder were divided into the core premenstrual disorder group and the premenstrual exacerbation group. We compared the mental health and quality of life scores calculated from the questionnaire between the two groups. Among the patients diagnosed with premenstrual disorders, about one-third were patients with premenstrual exacerbation. The premenstrual exacerbation group were more anxious and depressed than the core premenstrual disorder group, and had lower quality of life scores in almost all domains. The results underscore the importance that health care providers should always consider the possibility of premenstrual exacerbation when managing patients with premenstrual symptoms and provide appropriate care for these patients.

Two-component regulatory system TCS08 of a serotype 4 strain in pneumococcal pneumonia pathogenesis.

OBJECTIVES: Streptococcus pneumoniae, a human respiratory pathogen, causes diseases with severe morbidity and mortality rates worldwide. The two-component regulatory system (TCS) is an important signaling pathway that enables regulation of gene expression in response to environmental cues, thereby allowing an organism to adapt to a variety of host niches. Here we examined the contribution of pneumococcal TCS08 to bacterial colonization, the development of pneumonia, and pulmonary dysfunction. METHODS: We employed an hk08 knockout mutant (Δhk08) with a background of the TIGR4 wild-type (WT) strain to verify whether TCS08 is associated with bacterial colonization and the development of pneumonia in a murine infection model. To clarify the association of hk08 inactivation-induced phenotypic changes with their virulence, we examined pneumococcal capsule production, colony morphology, and surface-displayed protein profiles. RESULTS: Pneumococcal TCS08 was involved in bacterial colonization in the respiratory tract. Interruption of the signaling pathway of TCS08 by hk08 inactivation impaired mouse survival and increased the bacterial burden within the respiratory tract. Furthermore, a histopathological examination revealed massive inflammatory cell infiltration, edema formation, and diffuse alveolar damage in the lung tissues of mice infected with Δhk08 versus the WT or complemented strain. Interestingly, virulence-associated phenotype changes, including capsule production, increased chain length, and surface-displayed protein profile, were observed in the Δhk08 strain. CONCLUSIONS: The present findings indicate that TCS08 contributes to pneumococcal colonization and pulmonary dysfunction by assisting adaptation to the respiratory tract milieu, leading to the development of pneumonia.

Guideline for gynecological practice in Japan: Japan Society of Obstetrics and Gynecology and Japan Association of Obstetricians and Gynecologists 2023 edition.

Twelve years after the first edition of The Guideline for Gynecological Practice, which was jointly edited by The Japan Society of Obstetrics and Gynecology and The Japan Association of Obstetricians and Gynecologists, the 5th Revised Edition was published in 2023. The 2023 Guidelines includes 5 additional clinical questions (CQs), which brings the total to 103 CQ (12 on infectious disease, 30 on oncology and benign tumors, 29 on endocrinology and infertility and 32 on healthcare for women). Currently, a consensus has been reached on the Guidelines, and therefore, the objective of this report is to present the general policies regarding diagnostic and treatment methods used in standard gynecological outpatient care that are considered appropriate. At the end of each answer, the corresponding Recommendation Level (A, B, C) is indicated.

Efficacy and safety of olaparib, olaparib plus bevacizumab and niraparib maintenance treatment in Japanese patients with platinum-sensitive advanced ovarian cancer.

OBJECTIVE: To investigate whether maintenance treatment could be safely and effectively performed with olaparib, olaparib plus bevacizumab and niraparib in platinum-sensitive advanced ovarian cancer at multiple institutions in Japan. METHODS: We investigated progression-free survival and adverse events in 117 patients with platinum-sensitive advanced ovarian cancer treated with maintenance therapy. RESULTS: The median progression-free survival of 117 patients was 20.1 months. Patients with germline BRCA pathogenic variants had a significantly better prognosis than the other groups (P < 0.001). Furthermore, in the multivariate analysis, stage IV (P = 0.016) and germline BRCA wild-type (P ≤ 0.001) were significantly associated with worse progression-free survival in patients with advanced ovarian cancer. Regarding adverse events, all three types of maintenance treatment were significantly worse than chemotherapy given before maintenance treatment with respect to renal function (olaparib, P = 0.037; olaparib plus bevacizumab, P < 0.001; and niraparib, P = 0.016). CONCLUSION: Maintenance treatment was performed effectively and safely. Renal function deterioration is likely to occur during maintenance treatment, and careful administration is important in platinum-sensitive advanced ovarian cancer.

Relationship Between Hematological Toxicities During Maintenance Treatment and During Chemotherapy Before Maintenance Treatment in Patients With Platinum-sensitive Relapsed Ovarian Cancer.

BACKGROUND/AIM: To determine if maintenance treatment can be performed effectively and safely in patients with platinum-sensitive relapsed ovarian cancer. PATIENTS AND METHODS: We carried out a multi-center study to investigate progression-free survival (PFS) and adverse events (AEs) in 229 patients receiving maintenance treatment for platinum-sensitive relapsed ovarian cancer. RESULTS: The median PFS in the 229 patients with maintenance treatment was 14.0 months (95% confidence interval=10.3-17.6 months). The hematological toxicities included ≥grade 3 anemia in 33.2% of cases. Anemia during maintenance treatment was significantly more common than anemia during chemotherapy given before maintenance treatment (p<0.001). Anemia during chemotherapy prior to maintenance treatment significantly increased the risk of anemia during maintenance treatment, compared with other clinical features (p<0.001). CONCLUSION: Maintenance treatment can be performed safely and effectively in patients with platinum-sensitive relapsed ovarian cancer. Anemia during chemotherapy given before maintenance treatment significantly increased the risk of developing anemia during maintenance treatment in patients with platinum-sensitive relapsed ovarian cancer.

Effect of γ-tocopherol supplementation on premenstrual symptoms and natriuresis: a randomized, double-blind, placebo-controlled study.

BACKGROUND: This randomized, double-blind, placebo-controlled study aimed to investigate the effects of γ-tocopherol (Toc) supplementation on premenstrual symptoms and natriuresis. METHODS: We enrolled 51 Japanese women with premenstrual symptoms, particularly those who showed increased symptoms induced by water retention during the luteal phase compared with the follicular phase. Premenstrual symptoms were recorded in the first cycle's postmenstrual follicular phase; physical measurements and urine collection were conducted during the 48-h run-in period. The test supplement, which contained 180 mg of γ-Toc or placebo, was orally administered twice a day for 7 days during the luteal phase of the first and second cycles in a crossover manner. The same evaluation was conducted during the luteal phase, beginning in the morning of the sixth day of supplement administration. RESULTS: Compared with placebo intake, γ-Toc intake significantly reduced "fatigue" and "irritability/anger" symptoms. Furthermore, compared with placebo intake, γ-Toc intake significantly reduced the thigh circumference. Regarding the "swelling of the legs" and "heavy legs" symptoms and the thigh circumference, the biphasic trend of increasing and decreasing values in the daytime and morning, respectively, during the follicular phase was not observed at the luteal phase with placebo intake. Contrastingly, γ-Toc intake resulted in significantly lower values in the morning than placebo intake. The mean difference in 24-h urinary sodium excretion between γ-Toc and placebo intake was 10.6 mEq (95% confidence interval (CI): -0.1, 21.4, p = 0.05, power 55%). Plasma γ-Toc and its metabolite γ-carboxyethyl hydroxychroman (CEHC) levels were significantly higher with γ-Toc intake than with placebo intake. There were no significant between-supplement differences in serum electrolyte levels or cumulative urinary potassium excretion. CONCLUSION: γ-Toc intake could effectively alleviate certain premenstrual syndrome symptoms, particularly those related to water retention during the luteal phase. Furthermore, the underlying mechanism may involve the diuretic effect of γ-CEHC, which is a γ-Toc metabolite. TRIAL REGISTRATION: UMIN000047989; registration date: 10/06/2022, retrospectively registered.

Quantitative assessment of chest compression techniques on an infant manikin.

BACKGROUND: Current cardiopulmonary resuscitation (CPR) guidelines recommend the two-finger technique (TFT) of chest compression (CC) in infants for a single rescuer. We hypothesized that healthcare providers cannot achieve adequate CC depth with TFT, even if using real-time visual feedback (RVF). METHODS: This was a cross-over study, randomizing participants to perform three sets of 2-min continuous CC, comparing (i) TFT with RVF, (ii) the one-hand technique (OHT) without RVF, and (iii) OHT with RVF. A standard CPR trainer manikin of a 3-month-old infant and a monitor/defibrillator that displays and records the quantitative CC quality were used. We set a target compression depth of 40-50 mm and a target compression rate of 100-120/min. Data were analyzed using the Friedman test and Bonferroni correction. Statistical significance was defined as P-value of< 0.05. RESULTS: Fifty-nine healthcare providers participated in the study. The mean compression depth was 24 mm (interquartile range [IQR], 22-26 mm) in TFT with RVF and 43 mm (IQR, 38-48 mm) in OHT without RVF, P < 0.001. The proportion of adequate CC depth was 0% (IQR, 0-0%) in TFT with RVF, 22% (IQR, 5-54%) in OHT without RVF, and 62% (IQR, 29-83%) in OHT with RVF. The mean compression rate was within the target range in all three techniques. CONCLUSIONS: The TFT cannot produce the CC depth that meets the recommendation of the current CPR guidelines for an infant with RVF, whereas the OHT does.

Factors associated with xerostomia in perimenopausal women.

OBJECTIVES: Various oral symptoms, including xerostomia and burning mouth syndrome, may occur in menopausal women. These symptoms reduce quality of life (QOL). However, the actual condition of xerostomia after menopause is not clear. The purpose of this study was to reveal the factors associated with xerostomia in perimenopausal women. METHODS: Participants included 118 outpatients (mean age, 49.9 ± 3.2 years; range, 45-55 years) at a department of gynecology in Japan. Information was collected concerning age, medical history, medications, menstrual status, and history of treatment for climacteric symptoms. Oral symptoms, including xerostomia were evaluated with a 3-point scale. The climacteric symptom checklist for Japanese women and 36-Item Short-Form Health were used to evaluate climacteric symptoms and QOL, respectively. In addition, the volume of unstimulated saliva, oral moisture, salivary α-amylase, chromogranin A, and 17-ß estradiol were measured. RESULTS: Higher age, the total number of medications, psychotropic drug, hormone replacement therapy, treatment for climacteric symptoms, sticky mouth, burning sensation of tongue, dryness of nose and 14 of the 21 climacteric symptoms significantly affected xerostomia. In addition, treatment for climacteric symptoms, fall asleep but often awake at night, headaches and dryness of nose were significantly associated with xerostomia. In conclusion, xerostomia is closely associated to factors such as treatment for climacteric symptoms and certain menopausal symptoms, and it may be related to QOL in perimenopausal women.

Menopausal symptoms are associated with oral sensory complaints in perimenopausal women: an observational study.

BACKGROUND: Perimenopausal women experience a wide variety of systemic symptoms: hot flashes, sweating, mental health concerns and various oral sensory complaints (OSC). OSC in perimenopausal women include xerostomia, taste disturbance and burning mouth. However, the factors associated with these OSC have not been identified. The purpose of this investigation was to elucidate the factors associated with OSC in perimenopausal women. METHODS: The study cohort comprised 43 perimenopausal women aged 45-55 years. Data on medical history, medications, menstrual status, menopausal symptoms, quality of life, xerostomia, taste disturbance and burning mouth were collected. Volumes of unstimulated and stimulated saliva were measured. Tongue coating was evaluated according to a tongue coating index. Univariate analysis was performed to identify factors significantly associated with having xerostomia, taste disturbance, burning mouth and more than two OSC (2OSC). Next, the factors strongly associated with these symptoms were examined by logistic regression analysis. RESULTS: The number of menopausal symptoms was significantly higher, and volume of unstimulated saliva was significantly lower in participants with xerostomia, taste disturbance, burning mouth or 2OSC than in those without these characteristics. Agents targeting the central nervous system were more frequently taken by participants with burning mouth and 2OSC than by those without these characteristics. According to logistic regression analysis, the number of menopausal symptoms was an explanatory variable for xerostomia, taste disturbance, burning mouth and 2OSC. CONCLUSIONS: Our findings suggested that OSC associated with the number of menopausal symptoms. Management of menopausal symptoms may decrease OSC, leading to improved quality of life of perimenopausal women.

GP96 Drives Exacerbation of Secondary Bacterial Pneumonia following Influenza A Virus Infection.

Influenza A virus (IAV) infection predisposes the host to secondary bacterial pneumonia, known as a major cause of morbidity and mortality during influenza virus epidemics. Analysis of interactions between IAV-infected human epithelial cells and Streptococcus pneumoniae revealed that infected cells ectopically exhibited the endoplasmic reticulum chaperone glycoprotein 96 (GP96) on the surface. Importantly, efficient pneumococcal adherence to epithelial cells was imparted by interactions with extracellular GP96 and integrin αV, with the surface expression mediated by GP96 chaperone activity. Furthermore, abrogation of adherence was gained by chemical inhibition or genetic knockout of GP96 as well as addition of RGD peptide, an inhibitor of integrin-ligand interactions. Direct binding of extracellular GP96 and pneumococci was shown to be mediated by pneumococcal oligopeptide permease components. Additionally, IAV infection induced activation of calpains and Snail1, which are responsible for degradation and transcriptional repression of junctional proteins in the host, respectively, indicating increased bacterial translocation across the epithelial barrier. Notably, treatment of IAV-infected mice with the GP96 inhibitor enhanced pneumococcal clearance from lung tissues and ameliorated lung pathology. Taken together, the present findings indicate a viral-bacterial synergy in relation to disease progression and suggest a paradigm for developing novel therapeutic strategies tailored to inhibit pneumococcal colonization in an IAV-infected respiratory tract. IMPORTANCE Secondary bacterial pneumonia following an influenza A virus (IAV) infection is a major cause of morbidity and mortality. Although it is generally accepted that preceding IAV infection leads to increased susceptibility to secondary bacterial infection, details regarding the pathogenic mechanism during the early stage of superinfection remain elusive. Here, we focused on the interaction of IAV-infected cells and Streptococcus pneumoniae, which revealed that human epithelial cells infected with IAV exhibit a cell surface display of GP96, an endoplasmic reticulum chaperon. Notably, extracellular GP96 was shown to impart efficient adherence for secondary infection by S. pneumoniae, and GP96 inhibition ameliorated lung pathology of superinfected mice, indicating it to be a useful target for development of therapeutic strategies for patients with superinfection.

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Investigate the Effects of Kamishoyosan, a Traditional Japanese Medicine, on Menopausal Symptoms: The KOSMOS Study.

OBJECTIVE: The KOSMOS study, a multicenter, randomized, double-blind, placebo-controlled trial, investigated the effects and safety of kamishoyosan (TJ-24), a traditional Japanese medicine, in the treatment of climacteric disorder. METHODS: Japanese women with climacteric disorder were administered a placebo during a 4-week run-in period, after which they were classified as placebo responders (R group) if their score on the modified Questionnaire for the Assessment of Climacteric Symptoms in Japanese Women (m-QACS) with excitability and irritability as the primary outcome improved by ≥ 3 points and as placebo nonresponders (NR group) otherwise. Members of the NR group were randomly allocated to receive either TJ-24 or placebo. After 12 weeks, their m-QACS scores, anxiety and depression, sleep, and overall quality of life (QOL) were compared. RESULTS: The TJ-24 and placebo arms in the NR group included 20 patients each. The change in the m-QACS scores of members of the NR group for excitability and irritability at 12 weeks versus baseline was -3.1 ± 1.7 in the TJ-24 arm, a significant decrease, but compared with -2.7 ± 2.2 in the placebo arm, no significant difference was between two arms. However, the proportion of participants whose score improved by ≥3 points was significantly higher in the TJ-24 arm. In the subgroup analysis of premenopausal women, the changes in the score for excitability and irritability were significantly larger in the TJ-24 arm. The incidence of adverse drug reactions or adverse events did not differ between the two arms, and no serious events were reported. CONCLUSION: Although no significant difference was identified for the primary outcome, a significantly higher proportion of patients who received TJ-24 displayed improvement. Its high level of safety and effects on excitability and irritability in premenopausal women suggest that TJ-24 may be a useful treatment.

Guideline for Gynecological Practice in Japan: Japan Society of Obstetrics and Gynecology and Japan Association of Obstetricians and Gynecologists 2020 edition.

Nine years after the first edition of The Guideline for Gynecological Practice, which was jointly edited by The Japan Society of Obstetrics and Gynecology and The Japan Association of Obstetricians and Gynecologists, the 4th Revised Edition was published in 2020. The 2020 Guidelines includes 4 additional clinical questions (CQ), which brings the total to 99 CQ (12 on infectious disease, 29 on oncology and benign tumors, 29 on endocrinology and infertility and 29 on healthcare for women). Currently, a consensus has been reached on the Guidelines, and therefore, the objective of this report is to present the general policies regarding diagnostic and treatment methods used in standard gynecological outpatient care that are considered appropriate. At the end of each answer, the corresponding Recommendation Level (A, B, C) is indicated.

Effects of Kamishoyosan, a Traditional Japanese Medicine, on Menopausal Symptoms: A Randomized, Placebo-Controlled, Double-Blind Clinical Trial.

OBJECTIVE: Kampo medicine, a traditional Japanese medicine, is widely used in Japan, especially in the field of menopause medicine. However, few studies have shown evidence-based effects. This study aimed to confirm the effects of kamishoyosan on menopausal symptoms with a randomized, placebo-controlled, double-blind clinical trial. METHODS: Subjects were randomly allocated to groups that received either kamishoyosan (n = 101) or a placebo resembling kamishoyosan (n = 104). The primary outcomes were the change in the number of hot flashes, depression scores, improvements of anxiety, quality of life (QOL), and menopausal symptoms before and 4 and 8 weeks after initiation of treatment with the study drug. The secondary outcome was drug safety. RESULTS: After 8 weeks, the number of hot flashes decreased after treatment in both groups, but there was no significant difference between the two groups. The changes in SDS scores showed the same results. Moreover, no significant differences were observed between the two groups in assessments with the STAI, SF-36, and JSOG menopausal index. No serious adverse effect was reported. CONCLUSIONS: This first placebo-controlled double-blind randomized trial with kamishoyosan demonstrated that it was safe and had some effects on climacteric symptoms, but not significant compared with placebo. Some problems, such as placebo effects, in the study of Kampo therapy for menopausal symptoms, were revealed. This trial is registered with the trial registration number. UMIN 000006042.

Erratum to "Characterizations of oral microbiota in elderly nursing home residents with diabetes".

The publisher regrets that in the above-mentioned article, there was an error in the list of references. The reference numbers "29-32" should be "28-31".

Streptococcal Cysteine Protease-Mediated Cleavage of Desmogleins Is Involved in the Pathogenesis of Cutaneous Infection.

Streptococcus pyogenes is responsible for a wide variety of cutaneous infections ranging from superficial impetigo to fulminant invasive necrotizing fasciitis. Dysfunction of desmosomes is associated with the pathogenesis of cutaneous diseases. We identified streptococcal pyrogenic exotoxin B (SpeB) as a proteolytic factor that cleaves the extracellular domains of desmoglein 1 and 3. In an epicutaneous infection model, lesional skin infected with an speB deletion mutant were significantly smaller as compared to those caused by the wild-type strain. Furthermore, immunohistological analysis indicated cleavage of desmogleins that developed around the invasion site of the wild-type strain. In contrast, the speB mutant was preferentially found on the epidermis surface layer. Taken together, our findings provide evidence that SpeB-mediated degradation of desmosomes has a pathogenic role in development of S. pyogenes cutaneous infection.

Composition of salivary microbiota in elderly subjects.

Frailty is gaining attention worldwide with the aging of society. Despite the potential lethality and multiple signs and symptoms in affected individuals, preclinical detection of early manifestations leading to frailty syndrome have not been established. We speculated that the composition of the oral microbiota is associated with general frailty, as well as a relationship between gut microbiota and general health condition. In the present study, we investigated the salivary microbiota composition in samples from healthy and frail elderly individuals using 16S rRNA sequencing analysis for characterization. We found a significant difference in diversity between elderly individuals living in a nursing home (EN) and healthy control (HC) subjects, as well as in the microbiota composition at the phyla level. A supervised orthogonal partial least squared discriminant analysis (OPLS-DA) revealed a significant difference in clear classification trend between the EN and HC groups, with all observations falling within the Hotellings T2 (0.95) ellipse, with model fitness parameters of R 2(cum) = 0.937 and Q 2(cum) = 0.888, respectively. In addition, the score plots by unsupervised principal component analysis (PCA) showed a clear classification trend in both groups. Our findings suggest that general frailty is associated with oral microbiota composition and formation.

Characterizations of oral microbiota in elderly nursing home residents with diabetes.

Over 700 bacterial species have been detected in the oral cavity. Several studies have suggested that periodontitis is associated with systemic disorders such as diabetes mellitus, indicating a key role for oral microbiota in human health. However, the relationship between oral microbiota and diabetes has not been well clarified. Therefore, we conducted microbiome analysis of saliva samples obtained from 15 elderly residents (3 with type 2 diabetes mellitus [DM] and 12 without diabetes [non-DM]) at three different nursing homes, as well as 9 young healthy controls (HC). Genomic DNA was extracted from each sample, and then the V4 region of the 16S rRNA gene was amplified and sequenced. Alpha diversity, in terms of operational taxonomic unit richness, was significantly higher in samples from the non-DM group than in those from the HC group. Weighted UniFrac distance analysis showed that salivary microbial communities in the DM group were separately clustered. Furthermore, in the DM group, Actinomyces and Selenomonas showed significantly higher abundance, whereas Alloprevotella showed significantly lower abundance, relative to the non-DM group. Although our findings were limited by the small sample size, oral bacterial diversity in the DM group was clearly different from that in the non-DM group.

Cell type-specific effects of p27KIP1 loss on retinal development.

BACKGROUND: Cyclin-dependent kinase (CDK) inhibitors play an important role in regulating cell cycle progression, cell cycle exit and cell differentiation. p27KIP1 (p27), one of the major CDK inhibitors in the retina, has been shown to control the timing of cell cycle exit of retinal progenitors. However, the precise role of this protein in retinal development remains largely unexplored. We thus analyzed p27-deficient mice to characterize the effects of p27 loss on proliferation, differentiation, and survival of retinal cells. METHODS: Expression of p27 in the developing and mature mouse retina was analyzed by immunohistochemistry using antibodies against p27 and cell type-specific markers. Cell proliferation and differentiation were examined in the wild-type and p27-deficient retinas by immunohistochemistry using various cell cycle and differentiation markers. RESULTS: All postmitotic retinal cell types expressed p27 in the mouse retinas. p27 loss caused extension of the period of proliferation in the developing retinas. This extra proliferation was mainly due to ectopic cell cycle reentry of differentiating cells including bipolar cells, Müller glial cells and cones, rather than persistent division of progenitors as previously suggested. Aberrant cell cycle activity of cones was followed by cone death resulting in a significant reduction in cone number in the mature p27-deficient retinas. CONCLUSIONS: Although expressed in all retinal cell types, p27 is required to maintain the quiescence of specific cell types including bipolar cells, Müller glia, and cones while it is dispensable for preventing cell cycle reentry in other cell types.

Microbiological assessment of effects of clinical mouth rinses on common oral microbes.

Dry mouth occurs frequently in aged individuals, as well as in patients who are hospitalized, receiving multiple drugs, undergoing radiation treatment to the head and neck, or wearing a removable denture prosthesis, use of mouth rinse being often an option for relief. In the present study, we performed microbiological assessments of subjects given three different commercially available mouth rinses commonly employed in clinical practice (Peptisal, Biotène, ConCool) to determine their effects. For bacterial clearance in vitro, Peptisal showed the highest level of suppression of oral indigenous bacteria found in both planktonic formations and biofilm. Furthermore, the inhibitory effects of these agents on biofilm formation on acrylic resin plates were examined using scanning electron microscopy. Again, Peptisal proved superior, because acquisition of resistance to antimicrobial peptides by a sensitive microbial strain was rarely observed. We conclude that Peptisal is an effective mouth rinse for clearance of planktonic and biofilm microorganisms present in the oral cavity.