Dietary protein source strongly alters gut microbiota composition and function.

The source of protein in a persons diet affects their total life expectancy. However, the mechanisms by which dietary protein sources differentially impact human health and life expectancy are poorly understood. Dietary choices have major impacts on the composition and function of the intestinal microbiota that ultimately mediate host health. This raises the possibility that health outcomes based on dietary protein sources might be driven by interactions between dietary protein and the gut microbiota. In this study, we determine the effects of seven different sources of dietary protein on the gut microbiota in mice. We apply an integrated metagenomics-metaproteomics approach to simultaneously investigate the effects of these dietary protein sources on the gut microbiotas composition and function. The protein abundances measured by metaproteomics can provide microbial species abundances, and evidence for the phenotype of microbiota members on the molecular level because measured proteins allow us to infer the metabolic and physiological processes used by a microbial community. We showed that dietary protein source significantly altered the species composition and overall function of the gut microbiota. Different dietary protein sources led to changes in the abundance of microbial amino acid degrading proteins and proteins involved in the degradation of glycosylations on dietary protein. In particular, brown rice and egg white protein increased the abundance of amino acid degrading enzymes and egg white protein increased the abundance of bacteria and proteins usually associated with the degradation of the intestinal mucus barrier. These results show that dietary protein source can change the gut microbiotas metabolism, which could have major implications in the context of gut microbiota mediated diseases.

A critical examination of multidimensionality within the Hypomanic Personality Scale.

BACKGROUND: The Hypomanic Personality Scale (HPS) assesses bipolar spectrum psychopathology and risk for bipolar disorders. Despite the developers' intent to create a scale that provides a unitary score, several studies have examined whether the HPS has a multidimensional structure. These models have been unable to identify a replicable multidimensional structure, with models varying from fairly similar to entirely dissimilar, and have suffered from theoretical and methodological concerns. PROCEDURES: We therefore examined the multidimensional structure of the HPS in a large undergraduate and adult sample (n = 5002). MAIN FINDINGS: We failed to reproduce factors with equal congruence to those of previously published models. PRINCIPLE CONCLUSIONS: We concluded that the HPS lacks factorial validity in previous research as a multidimensional measure of bipolar spectrum psychopathology. We further recommend the creation of a novel multidimensional assessment of bipolar spectrum psychopathology developed from a theoretically driven, comprehensive model, rather than examining a multidimensional model of a pre-existing measure, such as the HPS.

Human papilloma virus and vaccine: knowledge and acceptability in an Irish general hospital-a questionnaire-based study.

BACKGROUND: In late 2019, Ireland extended its human papilloma virus (HPV) vaccine schedule to include boys of school age. AIMS: It is known that knowledge aids in vaccine acceptability [1], and as such, this study aimed to assess women's knowledge of HPV and the vaccine, and if they found the vaccine to be acceptable for both men and women. METHODS: This was a questionnaire-based study, which took place over a 6-month period in a general hospital. One hundred women attending the gynaecology clinic were asked to complete a twenty two question questionnaire, based on similar, validated questionnaires. Participants were included if over 18 years, female and capable of consenting. RESULTS: Responses were collected from n = 100 women. Questionnaires were distributed to 114 women. Fourteen women did not participate in the questionnaire, giving a response rate of 87.7%. Over 25% (n = 28) had never heard of the HPV vaccine. Of these, only one knew the risk factors for contracting HPV and only four, the diseases caused by HPV. Of this subgroup, 75% women responded 'I don't know' when asked if they think girls should receive the vaccine and 86% responded 'I don't know' with regards to boys receiving the vaccine. Of women who had heard of the vaccine (n = 74), 85% believed girls should receive the vaccine, while only 56% believed boys should. CONCLUSIONS: This study highlights the ongoing lack of knowledge surrounding HPV and the vaccine within this community. The importance of knowledge for vaccine acceptability is highlighted by vaccination considered less acceptable for boys. This may affect vaccine uptake within this subgroup and as such the authors suggest further education be directed towards boys.

Use of mechanical thresholds in a model of feline clinical acute pain and their correlation with the Glasgow Feline Composite Measure Pain Scale scores.

OBJECTIVES: The aim of this study was to evaluate the use of mechanical thresholds (MT), measured with the SMALGO (Small Animal ALGOmeter), and to determine whether there was a correlation between MT and Glasgow Feline Composite Measure Pain Scale (CMPS-Feline) scores in cats undergoing ovariohysterectomy. METHODS: Client-owned cats undergoing flank ovariohysterectomy were recruited. Pain scores for the pre- and postoperative periods were obtained using the CMPS-Feline in each cat by two independent investigators (A and B). Following CMPS-Feline scoring, MT were measured with the SMALGO, in the surgical area, pre- and postoperatively, only by investigator A. Each cat served as its own control for the comparison of pre- and postoperative variables. Reliability statistics were used to assess the level of inter-observer agreement (A vs B) with respect to pre- and postoperative CMPS-Feline scores, while Spearman's correlation statistics were used to analyse the relationship between MT and CMPS-Feline scores. RESULTS: Twenty-nine cats completed the study. Preoperative MT (340 g [range 108-691]) were significantly higher than postoperatively (233 g [range 19-549]; P = 0.001). CMPS-Feline scores were not found to differ significantly between the preoperative period (2 [range 0-7] for investigator A and 3.2 ± 2.3 for investigator B) and postoperative period (2 [range 0-10] for investigator A and 3 [range 0-8] for investigator B) for either investigator. Reliability statistics revealed that the level of inter-observer agreement with respect to CMPS-Feline was fair for the preoperative assessments but poor for the postoperative evaluations. There was no correlation between MT and CMPS-Feline scores. CONCLUSIONS AND RELEVANCE: Although there was no correlation with CMPS-Feline scores performed at the same timepoint, MT increased postoperatively vs baseline. Assuming that, despite analgesia, susceptibility of the surgical area to mechanical stimulation would increase after surgery, this finding suggests that MT might be useful to assess feline surgical pain. The poor level of inter-observer agreement with respect to postoperative CMPS-Feline scores highlights the potential limitations of this scale.

The etiology of stillbirth over 30 years: A cross-sectional study in a tertiary referral unit.

INTRODUCTION: Stillbirth remains an often unpredictable and devastating pregnancy outcome, and despite thorough investigation, the number of stillbirths attributable to unexplained causes remains high. Placental examination has become increasingly important where access to perinatal autopsy is limited. We aimed to examine the causes of stillbirth in normally formed infants over 30 years and whether a declining autopsy rate has affected our ability to determine a cause for stillbirths. MATERIAL AND METHODS: All cases of normally formed singleton infants weighing ≥500 g that died prior to the onset of labor from 1989 to 2018 were examined. Trends for specific causes and uptake of perinatal autopsy were analyzed individually. RESULTS: In all, 229 641 infants were delivered, with 840 stillbirths giving a rate of 3.66/1000. The rate of stillbirth declined from 4.84/1000 in 1989 to 2.51 in 2018 (P < .001). There was no difference in the rate of stillbirth between nulliparous and multiparous women (4.25 vs 3.66 per 1000, P = .026). Deaths from placental abruption fell (1.13/1000 in 1989 to 0 in 2018, P < .001) and the relative contribution of placental abruption to the incidence of stillbirth also fell, from 23.3% (7/30) in 1989 to 0.0% (0/19) in 2018 (P < .001). Stillbirth attributed to infection remained static (0.31/1000 in 1989 to 0.13 in 2018, P = .131), while a specific causal organism was found in 79.2% (42/53) of cases. Unexplained stillbirths decreased from 2.58/1000 (16/6200) in 1989 to 0.13 (1/7581) in 2018 (P < .001) despite a fall in the uptake of perinatal autopsy (96.7% [29/30] in 1989 to 36.8% (7/19) in 2018; P < .001). Placental disease emerged as a significant cause of stillbirth from 2004 onwards (89.5% [17/19] in 2018). CONCLUSIONS: The present analysis is one of the largest single-center studies on stillbirth published to date. Stillbirth rates have fallen across the study period across parity. A decrease in deaths secondary to placental abruption contributed largely to this. Infection-related deaths are static; however, in one-fifth of cases a causative organism was not found. Despite a decreasing autopsy rate, the number of unexplained stillbirths continues to fall as the importance of placental pathology is increasingly recognized.

Autophagy in the Aging and Experimental Ocular Hypertensive Mouse Model.

Purpose: To investigate autophagy in the outflow pathway and ganglion cell layer in the aging and ocular hypertensive mouse. Methods: Both 4-month-old and 18-month-old C57BL/6J and GFP-LC3 mice were subjected to unilateral injection of hypertonic saline into a limbal vein, causing sclerosis of the outflow pathway and subsequent elevation of intraocular pressure (IOP). IOP was measured on a weekly basis using a rebound tonometer. Protein expression levels of LC3B, Lamp1, and p62 were evaluated by western blot and/or immunofluorescence. Retinal ganglion cell (RGC) count was performed in whole retinal flat mounts using an anti-Brn3a antibody. Optic nerves were fixed with 4% paraformaldehyde and resin-embedded for axon counts and electron microscopy. Results: In contrast to 18-month-old mice, which developed sustained elevated IOP with a single injection, 4-month-old mice were refractory to high elevations of IOP. Interestingly, both the percentage of animals that developed elevated IOP and the mean ∆IOP were significantly higher in the transgenic mice compared to C57BL/6J. Immunofluorescence and western blot analysis showed dysregulated autophagy in the iridocorneal and retina tissues from 18-month-old mice compared to 4-month-old ones. Moreover, the LC3-II/LC3-I ratio correlated with IOP. As expected, injected hypertensive eyes displayed axonal degeneration and RGC death. RGC and axon loss were significantly exacerbated with aging, especially when combined with GFP-LC3 expression. Autophagic structures were observed in the degenerating axons. Conclusions: Our results indicate dysregulation of autophagy in the trabecular meshwork and retinal tissues with aging and suggest that such dysregulation of autophagy contributes to neurodegeneration in glaucoma.

Emotion dynamics concurrently and prospectively predict mood psychopathology.

INTRODUCTION: Altered emotion dynamics may represent a transdiagnostic risk factor for mood psychopathology. The present study examined whether altered emotion dynamics were associated with bipolar and depressive psychopathology concurrently and at a three-year follow-up. METHODS: At baseline (n = 138), participants completed diagnostic interviews, questionnaires, and seven days of experience sampling assessments. Four emotion dynamics were computed for negative affect (NA) and positive affect (PA) - within-person variance (variability), mean square of successive differences and probability of acute change (instability), and autocorrelation (inertia). At the three-year follow-up, participants (n = 108) were re-assessed via interviews and questionnaires. RESULTS: NA variability was associated with bipolar spectrum disorders at baseline and follow-up. NA instability predicted depressive symptoms and hypomanic personality at baseline, and bipolar spectrum disorders at the follow-up. NA inertia did not predict diagnoses or symptoms at either assessment. PA inertia predicted hyperthymic temperament at baseline but not follow-up. Notably, NA variability and instability predicted the development of new bipolar spectrum disorders at the follow-up. LIMITATIONS: Consistent with the recruitment strategy and young age of the participants, only 50% had developed diagnosable psychopathology by the time of the follow-up assessment. CONCLUSIONS: The present study provided a unique demonstration that altered emotion dynamics differentially predicted bipolar and depressive psychopathology concurrently and prospectively. Emotion dynamics are important to both digital phenotyping and mobile-based interventions as emotional instability offers a measurable risk factor that is identifiable prior to illness onset.

Cytokine biomarkers in tear film for primary open-angle glaucoma.

PURPOSE: To determine the utility of tear film cytokines as biomarkers for early primary open-angle glaucoma (POAG). METHODS: Patients without POAG and eye drop-naïve patients with newly diagnosed POAG were recruited from an academic hospital-based glaucoma practice. Tear films of recruited patients were obtained and analyzed using a multiplex, high-sensitivity electrochemiluminescent enzyme-linked immunosorbent assay for proinflammatory cytokines (IFNγ, IL-10, IL-12p70, IL-13, IL-1ß, IL-2, IL-4, IL-6, IL-8, and TNFα). RESULTS: Mean concentrations of tear film cytokines were lower in the glaucoma group for 8 of 10 cytokines tested. IL-12p70 (3.94±2.19 pg/mL in control vs 2.31±1.156 pg/mL in POAG; P=0.035) was significantly lower in the tear film of patients with newly diagnosed POAG. CONCLUSION: Proinflammatory cytokines were lower in eye drop-naïve newly diagnosed glaucoma patients. Tear film cytokine profiles may be used as biomarkers of early POAG.

A 3-Year Longitudinal Study of Risk for Bipolar Spectrum Psychopathology.

Current clinical and epidemiological research provides support for a continuum of bipolar psychopathology: a bipolar spectrum that ranges from subthreshold characteristics to clinical disorders. The present research examined risk for bipolar spectrum psychopathology at a 3-year follow-up assessment in a nonclinically ascertained sample of 112 young adults identified by the Hypomanic Personality Scale (HPS). Participants completed diagnostic interviews assessing bipolar psychopathology, borderline personality traits, substance use disorders, impulsivity, and psychosocial functioning. At the original assessment, 18 of the 112 participants met criteria for a bipolar spectrum disorder. At the follow-up, an additional 13 had developed bipolar spectrum disorders. A total of 58% of participants scoring in the upper quartile of the HPS qualified for bipolar spectrum disorders at the follow-up, including 27% with DSM­IV­TR disorders. The HPS predicted new cases and total number of cases of bipolar spectrum disorders, as well as total number of DSM­IV­TR bipolar disorders. The HPS also predicted hyperthymic temperament or history of hypomania, grandiose traits, impulsivity, substance use disorders, psychosocial impairment, and borderline traits. The majority of these effects were significant after removing participants with DSM­IV­TR bipolar disorders from the analyses, suggesting that the results were not driven by a subset of participants with clinical disorders. Overall, these results offer further support for the bipolar spectrum construct and the predictive validity of the HPS as a measure of bipolar spectrum psychopathology.

A three-year longitudinal study of affective temperaments and risk for psychopathology.

BACKGROUND: Affective temperaments are presumed to underlie bipolar psychopathology. The TEMPS-A has been widely used to assess affective temperaments in clinical and non-clinical samples. Cross-sectional research supports the association of affective temperaments and mood psychopathology; however, longitudinal research examining risk for the development of bipolar disorders is lacking. The present study examined the predictive validity of affective temperaments, using the TEMPS-A, at a three-year follow-up assessment. METHODS: The study interviewed 112 participants (77% of the original sample) at a three-year follow-up of 145 non-clinically ascertained young adults psychometrically at-risk for bipolar disorders, who previously took part in a cross-sectional examination of affective temperaments and mood psychopathology. RESULTS: At the reassessment, 29 participants (26%) met criteria for bipolar spectrum disorders, including 13 participants who transitioned into disorders during the follow-up period (14% of the originally undiagnosed sample). Cyclothymic/irritable and hyperthymic temperaments predicted both total cases and new cases of bipolar spectrum disorders at the follow-up. Cyclothymic/irritable temperament was associated with more severe outcomes, including DSM-IV-TR bipolar disorders, bipolar spectrum psychopathology, major depressive episodes, and substance use disorders. Hyperthymic temperament was associated with bipolar spectrum psychopathology and hypomania, whereas dysthymic temperament was generally unassociated with psychopathology and impairment. LIMITATIONS: The present sample of young adults is still young relative to the age of onset of mood psychopathology. CONCLUSIONS: These results provide the first evidence of the predictive validity of affective temperaments regarding risk for the development of bipolar psychopathology. Affective temperaments provide a useful construct for understanding bipolar psychopathology.

Risk factors for exposure of glaucoma drainage devices: a retrospective observational study.

OBJECTIVES: The purpose of this study was to identify risk factors for exposure of glaucoma drainage devices (GDD). SETTING: This retrospective, observational study was conducted in the eye clinic of an academic medical centre. PARTICIPANTS: Participants included 1073 consecutive adults who underwent GDD surgery between 1 January 2005 and 1 January 2011. Participants were included if chart review indicated GDD surgery during the study period and excluded if at least 12 months of clinical follow-up was not available in the medical record. PRIMARY OUTCOME MEASURE: The primary outcome measure was exposure of the GDD occurring at least 1 month after implant surgery. The characteristics of participants who experienced exposure of the implant were compared to the characteristics of participants who did not experience exposure. RESULTS: Of the 1073 participants having undergone GDD surgery, 67 experienced exposure of the device. Neither the type of GDD, type of patch graft (eye bank sclera, Tutoplast sclera and Tutoplast pericardium), surgeon, location of GDD, number of GDD previously implanted into the eye, nor history of diabetes or uveitis were associated with likelihood of exposure. Women were more likely than men to experience exposure of the GDD (OR 2.004 (95% CI1.170 to 3.431)) in both univariable (p=0.011) and multivariable (p=0.013) analyses. In survival analysis, exposure of the GDD occurred earlier for women than for men (58 vs 61 months; p=0.024).White race (vs black) was also associated with increased risk of GDD exposure (OR 1.693 (95% CI 1.011 to 2.833)) in univariable (p=0.044) and multivariable (p=0.046) analyses. CONCLUSIONS: Women are two times more likely to experience GDD exposure than men, independent of age. White race is also a risk factor for exposure.

Planned missing-data designs in experience-sampling research: Monte Carlo simulations of efficient designs for assessing within-person constructs.

Experience-sampling research involves trade-offs between the number of questions asked per signal, the number of signals per day, and the number of days. By combining planned missing-data designs and multilevel latent variable modeling, we show how to reduce the items per signal without reducing the number of items. After illustrating different designs using real data, we present two Monte Carlo studies that explored the performance of planned missing-data designs across different within-person and between-person sample sizes and across different patterns of response rates. The missing-data designs yielded unbiased parameter estimates but slightly higher standard errors. With realistic sample sizes, even designs with extensive missingness performed well, so these methods are promising additions to an experience-sampler's toolbox.

Affective temperaments: unique constructs or dimensions of normal personality by another name?

BACKGROUND: Current models theorize that affective temperaments underlie the development and expression of mood psychopathology. Recent studies support the construct validity of affective temperaments in clinical and non-clinical samples. However, one concern is that affective temperaments may be describing characteristics that are better captured by models of normal personality. We conducted two studies examining: (a) the association of affective temperaments with domains and facets of normal personality, and (b) whether affective temperaments accounted for variance in mood symptoms and disorders, impairment, and daily-life experiences over-and-above variance accounted for by normal personality. METHODS: Study 1 included 522 young adults who completed the TEMPS-A and the NEO-PI-3. Study 2 included 145 participants who were administered the TEMPS-A, NEO-FFI, interviews assessing psychopathology and impairment, and an assessment of daily life experiences. RESULTS: Study 1 revealed that personality domains and facets accounted for one-third to one-half of the variance in affective temperaments. However, study 2 demonstrated that affective temperaments accounted for unique variance in measures of psychopathology, impairment, and daily-life experiences after partialling variance associated with personality domains. Specifically, cyclothymic/irritable temperament predicted bipolar disorders, impairment, borderline personality traits, urgency, and anger in daily life. Hyperthymic temperament predicted hypomanic episodes, grandiosity, sensation seeking, and increased activity in daily life. LIMITATIONS: The study was limited by the fact that only domain, not facet-level, measures of FFM were available in study 2. CONCLUSIONS: The findings support the validity of hyperthymic and cyclothymic/irritable temperaments as indicators of clinical psychopathology and indicate that they provide information beyond normal personality.

The expression of affective temperaments in daily life.

BACKGROUND: Numerous validation studies have examined the TEMPS-A in both clinical and nonclinical samples. However, the majority of these studies utilized cross-sectional assessments in laboratory or clinical settings. The present study is the first to examine the expression of affective temperaments in daily life using experience sampling methodology (ESM). METHODS: 138 participants completed the TEMPS-A and received a personalized digital assistant that signaled them eight times daily for one week to complete questionnaires that assessed affect, cognition, behavior, sense of self, and social interaction. RESULTS: As expected, cyclothymic/irritable temperament was positively associated with negative affect, risky behavior, and restlessness, and was negatively associated with positive affect and preference to be with others in daily life. In contrast, hyperthymic temperament was associated with positive affect, fullness of thought, doing many and exciting things, grandiosity, and preference to be with others in daily life. Dysthymic temperament was modestly associated with worry, and was positively associated with trouble concentrating, fullness of thought, and a preference for social contact. Cross-level interactions indicated that cyclothymic/irritable temperament was associated with elevated stress reactivity in daily life. LIMITATIONS: ESM data collection was limited to one week. Longer assessment periods might better capture the cyclical nature of affective temperaments. CONCLUSIONS: This was the first study to examine affective temperaments in daily life. The findings offer further validation of the TEMPS-A, as well as the maladaptive nature of the cyclothymic/irritable temperament.

The association of affective temperaments with impairment and psychopathology in a young adult sample.

BACKGROUND: Previous research has examined the association of affective temperaments, as measured by the TEMPS-A, with DSM bipolar disorders. However, the relation of the TEMPS-A with risk for bipolar disorder remains unclear. The present study examined the association of affective temperaments with psychopathology, personality, and functioning in a nonclinically ascertained sample of young adults at risk for bipolar disorder. METHODS: One hundred forty-five participants completed the TEMPS-A, as well as interview and questionnaire measures of psychopathology, personality, and functioning. RESULTS: Cyclothymic/irritable temperament was associated with a range of deleterious outcomes, including mood disorders and impaired functioning. It was negatively associated with agreeableness and conscientiousness, and positively associated with current depressive symptoms, neuroticism, borderline symptoms, impulsivity, and grandiosity. Dysthymic temperament was positively associated with current depressive symptoms, neuroticism and agreeableness, but was unrelated to mood psychopathology. Hyperthymic temperament was associated with bipolar spectrum disorders, hypomania or interview-rated hyperthymia, extraversion, openness, impulsivity, and grandiosity. LIMITATIONS: The present study was cross-sectional. Longitudinal studies utilizing the TEMPS-A are needed to better understand the predictive validity of the TEMPS-A for the development of bipolar disorder. CONCLUSIONS: Early identification of individuals who fall on the bipolar spectrum may hasten appropriate intervention or monitoring, and prevent misdiagnosis. The TEMPS-A appears to be a useful tool for assessing affective temperaments and bipolar spectrum psychopathology. The results support previous research documenting the association of cyclothymic/irritable temperament with bipolar psychopathology and other negative outcomes.

Pilates for breast cancer survivors.

Pilates has been advocated for rehabilitation of breast cancer survivors despite little scientific evidence. The authors of this article have examined the feasibility of a Pilates program in postmastectomy breast cancer survivors and the impact on physical and psychological parameters. Fifteen breast cancer survivors were recruited in a one-arm study of 12 weeks of Pilates exercises. The authors assessed recruitment, adherence, and attrition, and measured changes in shoulder and neck range of motion, posture, height, arm volume, quality of life, mood, and body image from pre- to postintervention. Of 26 eligible patients, 15 enrolled, 13 completed the study, and 10 performed more than 50% of the recommended sessions. Statistically significant improvements emerged for shoulder abduction and internal rotation on the affected side, neck rotation toward the unaffected side, and neck flexion. The affected side arm volume and the interlimb volume discrepancy increased. Significant improvements were reported in quality of life, mood, and body image. The improvements in physical and psychological outcomes are promising and deserve further evaluation in a randomized, controlled study. The increase in affected arm volume also warrants additional investigation.

Looking for bipolar spectrum psychopathology: identification and expression in daily life.

OBJECTIVES: Current clinical and epidemiological research provides support for a continuum of bipolar psychopathology: a bipolar spectrum that ranges from subclinical manifestations to full-blown bipolar disorders. Examining subthreshold bipolar symptoms may identify individuals at risk for clinical disorders, promote early interventions and monitoring, and increase the likelihood of appropriate treatment. The present studies examined the construct validity of bipolar spectrum psychopathology using the Hypomanic Personality Scale. METHODS: Study 1 used interview and questionnaire measures of bipolar spectrum psychopathology in a sample of 145 nonclinically ascertained young adults. Study 2 assessed the expression of the bipolar spectrum in daily life using experience sampling methodology in the same sample. RESULTS: In study 1, Hypomanic Personality Scale scores were positively associated with clinical bipolar disorders, bipolar spectrum disorders, the presence of hypomania or hyperthymia, depressive symptoms, poor psychosocial functioning, cyclothymia, irritability, and symptoms of borderline personality disorder. In study 2, bipolar spectrum psychopathology was associated with negative affect, thought disturbance, risky behavior, and measures of grandiosity. These findings remained independent of clinical bipolar disorders. CONCLUSIONS: In the present studies, bipolar-like disruptions in cognition, affect, and behavior were not limited to clinical diagnoses or mood episodes, providing further validation of the bipolar spectrum construct. The bipolar spectrum model appears to provide a conceptually richer basis for understanding and ultimately treating bipolar psychopathology than current diagnostic formulations.

Prophylactic and therapeutic mastectomy in BRCA mutation carriers: can the nipple be preserved?

BACKGROUND: Use of nipple-sparing mastectomy (NSM) is increasing. We sought to look at the role of NSM in BRCA mutation carriers. METHODS: Tissue from women with a BRCA1 or BRCA2 mutation who underwent mastectomy between March 1987 and June 2009 at a single institution was reviewed. The entire nipple-areolar complex (NAC) was excised and histologically evaluated. The presence of terminal duct lobular units (TDLUs) and premalignant or malignant lesions in the NAC was noted. RESULTS: Sixty-two NACs from 33 women (25 BRCA1, 8 BRCA2) were studied. TDLUs were present in 15 (24%) NAC specimens. No evidence of atypical hyperplasia, carcinoma in situ, or invasive carcinoma was found in any of the 33 prophylactic mastectomy specimens. Among the 29 breasts with cancer and available tissue, 2 (7%) had malignant findings and 1 (3%) had atypia in the NAC. One woman who underwent bilateral mastectomy for bilateral invasive carcinoma had one nipple with tumor within lymphatics, and her contralateral nipple had atypical lobular hyperplasia. A second woman had ductal carcinoma in situ involving a single major lactiferous duct. CONCLUSIONS: The probability of nipple involvement by premalignant or malignant lesions in the NAC of BRCA mutation carriers is low at time of prophylactic mastectomy, but higher (10%) in women undergoing therapeutic mastectomy. NSM may be appropriate and oncologically safe for selected women with BRCA mutations. However, 24% of NACs contained TDLUs, with only 8% found in the nipple papilla; the significance of this for long-term risk is unknown.

Selective laser trabeculoplasty reduces mean IOP and IOP variation in normal tension glaucoma patients.

PURPOSE: To evaluate the effect of selective laser trabeculoplasty (SLT) in normal tension glaucoma (NTG) patients. PATIENTS AND METHODS: A retrospective review was performed of NTG patients who had undergone SLT at the Duke University Eye Center between 12/2002 and 7/2005. For each eye of each patient at pre-laser and post-laser time points, the IOP measurements were summarized by mean, standard deviation, and range. Then for each of these descriptive statistics, the differences between pre-laser and post-laser values were obtained. Statistical analysis was performed using a random effects model. MAIN OUTCOME MEASURES: difference in mean IOP, standard deviation of IOP, and range of IOP. RESULTS: Thirty-one eyes of 18 patients were included for analysis. The average of the mean pre-operative IOP measurements was 14.3 +/- 2.6 mmHg compared to 12.2 +/- 1.7 mmHg (P < 0.001) post-operatively. The mean pre-operative standard deviation was 1.9 +/- 0.9 mmHg compared to 1.0 +/- 0.6 mmHg (P = 0.002) post-operatively while the mean IOP range prior to treatment was 4.5 +/- 2.5 mmHg compared to 2.5 +/- 1.9 mmHg (P = 0.017) after treatment. CONCLUSION: In this pilot study, SLT was found to lower mean IOP and intervisit IOP variation in NTG patients. Given the importance of IOP variation and its association with glaucoma progression, measurement of IOP variation following treatment with SLT may be considered.

Gene and protein expression pilot profiling and biomarkers in an experimental mouse model of hypertensive glaucoma.

Glaucoma is a group of genetically heterogeneous neurodegenerative disorders causing the degeneration of the ganglion neurons of the retina. Increased intraocular pressure (IOP) is a hallmark risk factor promoting the death of ganglion neurons of the retina in glaucoma. Yet, the molecular processes underlying the degeneration of these neurons by increased IOP are not understood. To gain insight into the early molecular events and discover biomarkers induced by IOP, we performed gene and protein expression profiling to compare retinas of eyes with and without high IOP in a rodent model of experimental glaucoma. This pilot study found that the IOP-mediated changes in the transcription levels of a restricted set of genes implicated in peroxisomal and mitochondrial function, modulation of neuron survival and inflammatory processes, were also accompanied by changes in the levels of proteins encoded by the same genes. With the exception of the inflammatory markers, serum amyloid-A1 (SAA1) and serum amyloid-A2 (SAA2), the IOP-induced changes in protein expression were restricted to ganglion neurons of the retina and they were detected also in the vitreous, thus suggesting an early IOP-mediated loss of ganglion cell integrity. Interestingly, SAA1 and SAA2 were induced in retinal microglia cells, whereas they were reduced in sera of IOP-responsive mice. Hence, this study defines novel IOP-induced molecular processes, biomarkers and sources thereof, and it further validates the extension of the analyses herein reported to other genes modulated by IOP.