The Implications of Mental Health and Trauma in Interstitial Cystitis.

This review aims to assess the relationship between interstitial cystitis (IC) and significant traumatic events or PTSD. It was shown that there is a strong correlation between past trauma and the development of interstitial cystitis, as well as a much higher incidence of PTSD in patients diagnosed with IC. It was also established that for individuals with early traumatic experiences, the more likely the development of IC later in life, and with more severe symptoms and adverse effects on quality of life. We describe three distinct hypotheses for the possible physiologic mechanism for development of IC with relation to mental health and trauma, although definitive evidence in this area is still lacking, which poses interesting avenues for further research. This review also revealed an apparent lack of, and need for, trauma informed care and screening for PTSD in patients diagnosed with IC or other chronic pain syndromes.

An in vitro acoustic analysis and comparison of popular stethoscopes.

PURPOSE: To compare the performance of various commercially available stethoscopes using standard acoustic engineering criteria, under recording studio conditions. MATERIALS AND METHODS: Eighteen stethoscopes (11 acoustic, 7 electronic) were analyzed using standard acoustic analysis techniques under professional recording studio conditions. An organic phantom that accurately simulated chest cavity acoustics was developed. Test sounds were played via a microphone embedded within it and auscultated at its surface by the stethoscopes. Recordings were made through each stethoscope's binaurals and/or downloaded (electronic models). Recordings were analyzed using standard studio techniques and software, including assessing ambient noise (AMB) rejection. Frequency ranges were divided into those corresponding to various standard biological sounds (cardiac, respiratory, and gastrointestinal). RESULTS: Loudness and AMB rejection: Overall, electronic stethoscopes, when set to a maximum volume, exhibited greater values of perceived loudness compared to acoustic stethoscopes. Significant variation was seen in AMB rejection capability. Frequency detection: Marked variation was also seen, with some stethoscopes performing better for different ranges (eg, cardiac) vs others (eg, gastrointestinal). CONCLUSION: The acoustic properties of stethoscopes varied considerably in loudness, AMB rejection, and frequency response. Stethoscope choice should take into account clinical conditions to be auscultated and the noise level of the environment.

Schooling diabetes: Use of continuous glucose monitoring and remote monitors in the home and school settings.

BACKGROUND: Despite significant advances in type 1 diabetes (T1D) management, achieving targeted glycemic control in pediatric patients remains a struggle. Continuous glucose monitoring (CGM) with remote access holds the promise to address this challenge by allowing caregivers to monitor glucose, even when the child is not directly under their supervision. OBJECTIVE: To explore real-time and remote CGM practices in homes and schools, including caregiver expectations regarding this technology. SUBJECTS: Parents and daytime caregivers. METHODS: Respondents answered an anonymous survey assessing characteristics of CGM use. Cross-sectional data were collected and analyzed using quantitative and qualitative methods. RESULTS: Thirty-three parents and 17 daytime caregivers responded. Threshold alerts (alerts when patients reached certain pre-set high or low limits) were used most frequently, followed by rate of change alerts. Most parents and daytime caregivers responded to low- and high-threshold CGM alerts by confirming with a glucose meter prior to treatment; while about one-third endorsed treating lows without a confirmatory test. Most parents expected their child's daytime caregiver to respond to CGM alerts and daytime caregivers felt the parent's expectations of them were reasonable. All parents and most caregivers reported decreased overall worry/stress. Parents felt positive about CGM use and daytime caregivers felt comfortable with CGM. CONCLUSION: The positive and collaborative management reported by parents and daytime caregivers sets the stage for CGM to play an important role in the management of children with T1D both in the home and in the school settings.

Aberrant subcellular localization of SQSTM1/p62 contributes to increased vulnerability to proteotoxic stress recovery in Huntington's disease.

Proteotoxic stress plays an important role in the pathogenesis of Huntington's disease (HD). Autophagy is proposed as a compensatory mechanism to remove protein aggregates under proteotoxic stress by up-regulating p62 expression. In the present study, we investigated the molecular action of p62 to proteotoxic stress in HD cells. Using two different HD cellular models, STHdhQ7 and STHdhQ111 cells derived from wild type and HD knock-in mice and human fibroblasts from healthy and HD patients, we found that HD cells are more vulnerable to cell death under proteotoxic stress and during stress recovery. We further showed that P62 was up-regulated in both STHdhQ7 and STHdhQ111 cells in response to the stress with distinct subcellular localization patterns. While dispersed p62 puncti were found in STHdhQ7 cells, p62 bodies were initially present in the lysosomes and accumulated to the juxtanuclear regions of STHdhQ111 cells as MG132 incubation continued. Unlike in STHdhQ7 cells, p62 puncti were not associated with K48-linked polyubiquitinated protein aggregates or proteasomal components in STHdhQ111. Interestingly, addition of cysteine during MG132 incubation rescued cell death in STHdhQ111 cells caused by stress recovery and altered the subcellular distribution of p62. Our data suggest that aberrant positioning of p62 affects the proteasomal clearance of protein aggregates and may contribute to the increased vulnerability to proteotoxic stress-induced cell death in HD cells.

Altered lysosomal positioning affects lysosomal functions in a cellular model of Huntington's disease.

Huntington's disease (HD) is a hereditary and devastating neurodegenerative disorder caused by a mutation in the huntingtin protein. Understanding the functions of normal and mutant huntingtin protein is the key to revealing the pathogenesis of HD and developing therapeutic targets. Huntingtin plays an important role in vesicular and organelle trafficking. Lysosomes are dynamic organelles that integrate several degradative pathways and regulate the activity of mammalian target of rapamycin complex 1 (mTORC1). In the present study, we found that the perinuclear accumulation of lysosomes was increased in a cellular model of HD derived from HD knock-in mice and primary fibroblasts from an HD patient. This perinuclear lysosomal accumulation could be reversed when normal huntingtin was overexpressed in HD cells. When we further investigated the functional significance of the increased perinuclear lysosomal accumulation in HD cells, we demonstrated that basal mTORC1 activity was increased in HD cells. In addition, autophagic influx was also increased in HD cells in response to serum deprivation, which leads to premature fusion of lysosomes with autophagosomes. Taken together, our data suggest that the increased perinuclear accumulation of lysosomes may play an important role in HD pathogenesis by altering lysosomal-dependent functions.