Bone Vasculature and Bone Marrow Vascular Niches in Health and Disease

Bone vasculature and bone marrow vascular niches supply oxygen, nutrients, and secrete angiocrine factors required for the survival, maintenance, and self-renewal of stem and progenitor cells. In the skeletal system, vasculature creates nurturing niches for bone and blood-forming stem cells. Blood vessels regulate hematopoiesis and drive bone formation during development, repair, and regeneration. Dysfunctional vascular niches induce skeletal aging, bone diseases, and hematological disorders. Recent cellular and molecular characterization of the bone marrow microenvironment has provided unprecedented insights into the complexity, heterogeneity, and functions of the bone vasculature and vascular niches. The bone vasculature is composed of distinct vessel subtypes that differentially regulate osteogenesis, hematopoiesis, and disease conditions in bones. Further, bone marrow vascular niches supporting stem cells are often complex microenvironments involving multiple different cell populations and vessel subtypes. This review provides an overview of the emerging vascular cell heterogeneity in bone and the new roles of the bone vasculature and associated vascular niches in health and disease. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

COVID-19 Gender Disparities and Mitigation Recommendations: A Narrative Review

The coronavirus disease 2019 (COVID-19) pandemic has rapidly created widespread impacts on global health and the economy. Data suggest that women are less susceptible to severe illness. However, sex-disaggregated data are incomplete, leaving room for misinterpretation, and focusing only on biologic sex underestimates the gendered impact of the pandemic on women. This narrative review summarizes what is known about gender disparities during the COVID-19 pandemic and the economic, domestic, and health burdens along with overlapping vulnerabilities related to the pandemic. In addition, this review outlines recommended strategies that advocacy groups, community leaders, and policymakers should implement to mitigate the widening gender disparities related to COVID-19.     

Maladaptive behaviors in individuals with Angelman syndrome

Maladaptive behaviors are challenging and a source of stress for caregivers of individuals with Angelman Syndrome (AS). There is limited information on how these maladaptive behaviors vary over time among individuals with AS due to different genetic etiologies. In this study, caregivers of 301 individuals with AS were asked questions about their child's behavior and completed the Aberrant Behavior Checklist‐Community version (ABC‐C). Developmental functioning was evaluated with either the Bayley Scales of Infant Development, Third Edition (Bayley‐III) or the Mullen Scales of Early Learning (MSEL). Family functioning was assessed using the parent‐completed Parenting Stress Index (PSI) and the Family Quality of Life questionnaire (FQoL). Approximately 70% of participants had AS due to a deletion on the maternally‐inherited copy of chromosome 15q11q13. Results revealed that at baseline, individuals with AS had low scores in the domains of lethargy (mean: 2.6–4.2 depending on genotype) and stereotypy (mean: 2.3–4.2 depending on genotype). Higher cognitive functioning was associated with increased irritability (r = 0.32, p < .01). Hyperactivity (p < .05) and irritability (p < .05) increased with age across all genotypes and should be ongoing targets for both behavioral and pharmacological treatment. Concerns for short attention span were endorsed by more than 70% of caregivers at baseline. Maladaptive behaviors, particularly hyperactivity, irritability and aggression, adversely affected parental stress, and family quality of life.     

Short-term clinical outcomes and patient compliance with temporomandibular disorder treatment recommendations

AIMS: To evaluate short-term patient compliance with 5 conservative temporomandibular disorder (TMD) treatments (jaw relaxation, jaw stretching, heat application, cold application, and occlusal splint use) and the association of compliance with changes in pain intensity, pain-related activity interference, and jaw use limitations. METHODS: Eighty-one TMD patients were given 1 to 5 treatment recommendations as part of usual care in a TMD specialty clinic. Compliance with each recommendation and pain, pain-related activity interference, and jaw use limitation measures were calculated from electronic interviews conducted 3 times daily for 2 weeks. RESULTS: Median compliance with individual treatment modalities ranged from 7.7% for heat application to 92.7% for jaw relaxation; median overall compliance was 54.8%. Participants with higher initial pain intensity and jaw use limitations were significantly more compliant with their recommended treatment regimen (P < .05). The authors controlled for age, gender, education, and initial jaw use limitations. Overall compliance was associated significantly and positively with 2-week jaw use limitations (P = .03). A trend toward a statistically significant positive association was found between compliance and 2-week pain intensity (P = .09). CONCLUSION: Compliance varied widely across patients and therapies. Patients with higher initial pain and jaw use limitation levels were more compliant with treatment recommendations. Although compliance was associated with slight increases in pain and jaw use limitations in this preliminary study, further research is needed to evaluate the longer-term effects of compliance with recommended therapies.     

Changes in human brain glutamate concentration during hypoglycemia: insights into cerebral adaptations in hypoglycemia-associated autonomic failure in type 1 diabetes

Hypoglycemia-associated autonomic failure (HAAF) is a condition in which patients with type 1 diabetes (T1D) who experience frequent hypoglycemia develop defective glucose counter-regulation and become unable to sense hypoglycemia. Brain glutamate may be involved in the mechanism of HAAF. The goal of this study was to follow the human brain glutamate concentration during experimentally induced hypoglycemia in subjects with and without HAAF. ¹H magnetic resonance spectroscopy was used to track the occipital cortex glutamate concentration throughout a euglycemic clamp followed immediately by a hypoglycemic clamp. T1D patients with HAAF were studied in comparison to two control groups, i.e., T1D patients without HAAF and healthy controls (n=5 per group). Human brain glutamate concentration decreased (P⩽0.01) after the initiation of hypoglycemia in the two control groups, but a smaller trend toward a decrease in patients with HAAF did not reach significance (P>0.05). These findings are consistent with a metabolic adaptation in HAAF to provide higher glucose and/or alternative fuel to the brain, eliminating the need to oxidize glutamate. In an exploratory analysis, we detected additional metabolite changes in response to hypoglycemia in the T1D patient without HAAF control group, namely, increased aspartate and decreased lactate.     

Frontal and temporal contributions to understanding the iconic co‐speech gestures that accompany speech

In everyday conversation, listeners often rely on a speaker's gestures to clarify any ambiguities in the verbal message. Using fMRI during naturalistic story comprehension, we examined which brain regions in the listener are sensitive to speakers' iconic gestures. We focused on iconic gestures that contribute information not found in the speaker's talk, compared with those that convey information redundant with the speaker's talk. We found that three regions—left inferior frontal gyrus triangular (IFGTr) and opercular (IFGOp) portions, and left posterior middle temporal gyrus (MTGp)—responded more strongly when gestures added information to nonspecific language, compared with when they conveyed the same information in more specific language; in other words, when gesture disambiguated speech as opposed to reinforced it. An increased BOLD response was not found in these regions when the nonspecific language was produced without gesture, suggesting that IFGTr, IFGOp, and MTGp are involved in integrating semantic information across gesture and speech. In addition, we found that activity in the posterior superior temporal sulcus (STSp), previously thought to be involved in gesture‐speech integration, was not sensitive to the gesture‐speech relation. Together, these findings clarify the neurobiology of gesture‐speech integration and contribute to an emerging picture of how listeners glean meaning from gestures that accompany speech. Hum Brain Mapp 35:900–917, 2014. © 2012 Wiley Periodicals, Inc.     

Surgical Outcomes of Primary Versus Post-Neoadjuvant Chemotherapy Breast Conservation Surgery: A Comparative Study from a Developing Country

Introduction

In India and other developing countries, breast conservation surgery (BCS) rates in breast cancer patients are low due to advanced disease at presentation and misconceptions about BCS outcomes. Many patients presenting with large or locally advanced breast cancers (LABC) can be offered post-neoadjuvant chemotherapy (NACT) BCS, safety of which is not as well established as that of primary BCS. This retrospective study compared pathological and surgical outcome parameters in patients undergoing primary and post-NACT BCS.

Methods

All non-metastatic breast cancer patients undergoing BCS during 2011–2015 with 1-year follow-up were included. Outcome parameters in form of margin infiltration, ipsilateral breast tumor recurrence (IBTR) rates and IBTR-free survival were compared between primary and post-NACT BCS patients groups.

Results

One hundred and twenty-nine patients underwent BCS; 95 underwent primary and 34 post-NACT BCS. Patients in both groups underwent similar multimodality treatment as per institutional protocols. Post-NACT patients more frequently required oncoplastic volume displacement or replacement surgery (p = 0.002). Re-excision of infiltrated margins was needed more frequently in primary BCS compared with post-NACT BCS group (14.4 vs. 8.8%; p = 0.40). IBTR (Mean follow-up = 30.7 months) was seen in 8.8% post-NACT patients compared with 2.1% primary BCS (p = 0.114). IBTR-free survival did not differ significantly between the groups in stage-wise comparison.

Conclusion

Post-NACT BCS is safe even in large tumors and LABC, though many require oncoplastic procedures for satisfactory cosmesis. In a developing country where many patients present with large breast cancers or LABC, the benefits of BCS can be offered to a majority with the help of NACT, without compromising the chances of cure.

     

Association of high-sensitivity C-reactive protein and odds of breast cancer by molecular subtype: analysis of the MEND study

Breast cancer (BC) in Nigeria is characterized by disproportionately aggressive molecular subtypes. C-reactive protein (CRP) is associated with risk and aggressiveness for several types of cancer. We examined the association of high-sensitivity CRP (hsCRP) with odds of BC by molecular subtype among Nigerian women. Among 296 newly diagnosed BC cases and 259 healthy controls, multivariable logistic regression models were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the association between hsCRP and odds of BC overall and by molecular subtype (luminal A, luminal B, HER2-enriched and triple-negative or TNBC). High hsCRP (> 3 mg/L) was observed in 57% of cases and 31% of controls and was associated with 4 times the odds of BC (aOR: 4.43; 95% CI: 2.56, 7.66) after adjusting for socio-demographic, reproductive, and clinical variables. This association persisted regardless of menopausal status and body mass index (BMI) category. High hsCRP was associated with increased odds of TNBC (aOR: 3.32; 95% CI: 1.07, 10.35), luminal A BC (aOR: 4.03; 95% CI: 1.29, 12.64), and HER2-enriched BC (aOR: 6.27; 95% CI: 1.69, 23.25). Future studies are necessary in this population to further evaluate a potential role for CRP as a predictive biomarker for BC.