Development and Evaluation of Calcium-Fortified Multi-Millet Biscuits: A Nutritious Alternative to Refined Wheat Flour.

Millet products have garnered global recognition for their exceptional nutritional profile, appealing to various age demographics, and, therefore, fortifying such products with minerals can ensure nutritional security. This research explores the feasibility of utilizing millet as a substitute for refined wheat flour in biscuit production. Three distinct millet varieties were investigated: finger, pearl, and buckwheat. Employing response surface methodology (RSM), the optimal ratio of these flours was determined, resulting in a blend of 1.5:1:1, respectively. The optimized multi-millet biscuits were further enhanced with calcium fortification and subjected to comprehensive physico-chemical analysis. Proximate composition analysis revealed favorable levels of protein (5.472 ± 0.31%), ash (2.80 ± 0.57 g/100 g), and energy density (5.8015 ± 0.004 kcal/g), indicating a significantly higher protein content, enriched mineral profile, and high energy density as compared to refined wheat flour products. Sensory evaluation encompassing attributes such as color and texture and organoleptic assessment using a nine-point hedonic scale demonstrated favorable acceptance. Additionally, the overall acceptability of the biscuits remained consistently high throughout storage, ranging from 8.263 ± 0.65 (day 0) to 8.053 ± 0.85 (day 14). This study underscores the potential of multi-millet biscuits as a nutritious and palatable alternative to traditional wheat-based snacks, offering an avenue for diversifying dietary options and promoting healthier food choices.

Osteochondroprogenitor cells and neutrophils expressing p21 and senescence markers modulate fracture repair.

Cells expressing features of senescence, including upregulation of p21 and p16, appear transiently following tissue injury, yet the properties of these cells or how they contrast with age-induced senescent cells remains unclear. Here, we used skeletal injury as a model and identified the rapid appearance following fracture of p21+ cells expressing senescence markers, mainly as osteochondroprogenitors (OCHs) and neutrophils. Targeted genetic clearance of p21+ cells suppressed senescence-associated signatures within the fracture callus and accelerated fracture healing. By contrast, p21+ cell clearance did not alter bone loss due to aging; conversely, p16+ cell clearance, known to alleviate skeletal aging, did not affect fracture healing. Following fracture, p21+ neutrophils were enriched in signaling pathways known to induce paracrine stromal senescence, while p21+ OCHs were highly enriched in senescence-associated secretory phenotype factors known to impair bone formation. Further analysis revealed an injury-specific stem cell-like OCH subset that was p21+ and highly inflammatory, with a similar inflammatory mesenchymal population (fibro-adipogenic progenitors) evident following muscle injury. Thus, intercommunicating senescent-like neutrophils and mesenchymal progenitor cells were key regulators of tissue repair in bone and potentially across tissues. Moreover, our findings established contextual roles of p21+ versus p16+ senescent/senescent-like cells that may be leveraged for therapeutic opportunities.

Vocal repertoire of Microhyla nilphamariensis from Delhi and comparison with closely related M. ornata populations from the western coast of India and Sri Lanka.

Advertisement calls in frogs have evolved to be species-specific signals of recognition and are therefore considered an essential component of integrative taxonomic approaches to identify species and delineate their distribution range. The species rich genus Microhyla is a particularly challenging group for species identification, discovery and conservation management due to the small size, conserved morphology and wide distribution of its members, necessitating the need for a thorough description of their vocalization. In this study, we provide quantitative description of the vocal behaviour of Microhyla nilphamariensis, a widely distributed south Asian species, from Delhi, India, based on call recordings of 18 individuals and assessment of 21 call properties. Based on the properties measured acrossed 360 calls, we find that a typical advertisement call of M. nilphamariensis lasts for 393.5 ±  57.5 ms, has 17 pulses on average and produce pulses at rate of 39 pulses/s. The overall call dominant frequency was found to be 2.8 KHz and the call spectrum consisted of two dominant frequency peaks centered at 1.6 KHz and 3.6 KHz, ranging between 1.5-4.1 KHz. Apart from its typical advertisement call, our study also reveals the presence of three 'rare' call types, previously unreported in this species. We describe variability in call properties and discuss their relation to body size and temperature. We found that overall dominant frequency 1 (spectral property) was found to be correlated with body size, while first pulse period (temporal property) was found to be correlated with temperature. Further, we compare the vocal repertoire of M. nilphamariensis with that of the congener Microhyla ornata from the western coast of India and Sri Lanka and also compare the call properties of these two populations of M. ornata to investigate intra-specific call variation. We find statistically significant differentiation in their acoustic repertoire in both cases. Based on 18 call properties (out of 20), individuals of each locality clearly segregate on PCA factor plane forming separate groups. Discriminant function analysis (DFA) using PCA factors shows 100% classification success with individuals of each locality getting classified to a discrete group. This confirms significant acoustic differentiation between these species as well as between geographically distant conspecifics. The data generated in this study will be useful for comparative bioacoustic analysis of Microhyla species and can be utilized to monitor populations and devise conservation management plan for threatened species in this group.

Bias and Conflict of Interest in the Underreporting of Sexual Abuse in Competitive Sports: A Literature Review.

ABSTRACT: The prevalence of sexual abuse in competitive sports is increasing worldwide and requires a united call to action. The underreporting of such abuses gained media attention resulting from recent high-profile cases. In this article, we report the results of a systematic literature review, identifying root causes of underreporting sexual abuse in competitive sports. We identify that biases and conflicts of interest work against effective reporting of abuse by athletes at the individual, organizational, and cultural levels. We offer conflict of interest and bias mitigation approaches from the social science, law, business, research, and diagnostic error literature that may apply. Competitive sports organizations may use this analysis to identify barriers and improve the effective reporting of sexual abuse.

Can patient anthropometry predict the anterior cruciate ligament footprint dimensions? - An MRI-based observational study on north Indian population.

Background: Anterior Cruciate Ligament (ACL) reconstruction is one of the most common surgeries being currently done. As we usher into the era of Individualized Anatomic Reconstruction, it is very important to understand the native anatomy of ACL. We aimed to assess the ACL footprint dimensions in our patients and correlate it with anthropometric variables, which can help in preoperative decision making. Method: A total of 143 eligible patients with suspected ACL injury presented during the study period. Out of which 92 were included in the study. Data on patient's age, sex, height, weight and body mass index (BMI) was recorded. The length and area of both the tibial and femoral footprints were measured on MRI. The footprint dimensions were correlated with the recorded anthropometric data. Results: The ACL tibial footprint length and area, and femoral footprint length and area were found to be 13.3 ± 2.23 mm, 142.6 ± 26.16 mm2, 11.2 ± 1.97 mm, 125.8 ± 28.75 mm2 respectively. Footprint in males was significantly larger than females. A weak (ρ- 0.21 to 0.4) correlation with weight and moderate (ρ- 0.41 to 0.6) correlation with height was observed. Multivariate linear regression analysis yielded height to be the only significant predictor of footprint dimension from which predictive equations were drawn. Conclusions: Height was found to be the most significant predictor of footprint dimensions in our patients. The predictive equations and graphs can aid in preoperative surgical decision making resulting in a more anatomical ACL reconstruction and improve the post-operative results.

Osteochondroprogenitor cells and neutrophils expressing p21 and senescence markers modulate fracture repair.

Cells expressing features of senescence, including upregulation of p21 and p16, appear transiently following tissue injury, yet the properties of these cells or how they contrast with age-induced senescent cells remains unclear. Here, we used skeletal injury as a model and identified the rapid appearance following fracture of p21+ cells expressing senescence markers, mainly as osteochondroprogenitors (OCHs) and neutrophils. Targeted genetic clearance of p21+ cells suppressed senescence-associated signatures within the fracture callus and accelerated fracture healing. By contrast, p21+ cell clearance did not alter bone loss due to aging; conversely, p16+ cell clearance, known to alleviate skeletal aging, did not affect fracture healing. Following fracture, p21+ neutrophils were enriched in signaling pathways known to induce paracrine stromal senescence, while p21+ OCHs were highly enriched in senescence-associated secretory phenotype factors known to impair bone formation. Further analysis revealed an injury-specific stem cell-like OCH subset that was p21+ and highly inflammatory, with a similar inflammatory mesenchymal population (fibro-adipogenic progenitors) evident following muscle injury. Thus, intercommunicating senescent-like neutrophils and mesenchymal progenitor cells are key regulators of tissue repair in bone and potentially across tissues. Moreover, our findings establish contextual roles of p21+ vs p16+ senescent/senescent-like cells that may be leveraged for therapeutic opportunities.

Dorsal Wrist Carpal Boss Impingement-Dynamic Ultrasound to the Rescue!

The "carpal boss" is a variant present in 19% of the population according to cadaveric studies but becomes symptomatic in only 1% of cases. With the rising popularity of "yoga," which includes prolonged hyperextension at the wrist joint with weight bearing, an increasing number of individuals with silent carpal boss present with dorsal wrist pain due to impingement over the dorsal soft tissues by this innocuous bony protuberance. This warrants the attention of radiologists and clinicians while dealing with wrist pain. It can be challenging to identify this bossing on routine radiographs, necessitating special views. We describe the use of dynamic ultrasound in diagnosing "symptomatic" carpal boss, the effects of which become even more evident on imaging during hyperextension-the triggering movement.

Spontaneous splenic rupture due to Peliosis and the association with malignancy: A case series and literature review.

INTRODUCTION AND IMPORTANCE: Isolated splenic peliosis is an extremely rare condition. The associations of splenic peliosis with various infections, medications, and conditions have unclear significance. We present three patients from the past twenty years with spontaneous splenic rupture due to peliosis, two of whom had hematologic malignancy, to draw attention to a possible correlation. CASE PRESENTATION: A 31-year-old male with essential thrombocytopenia and antiphospholipid-antibody syndrome presented with worsening abdominal pain and hypotension. The patient denied any trauma. Computed-tomography demonstrated hemoperitoneum and splenic rupture with innumerable blood-filled splenic cysts. An uncomplicated emergency open splenectomy was performed with shed-blood reinfusion. The patient was discharged on postoperative day five. The patient developed acute myelogenous leukemia and died six years later. A 44-year-old otherwise healthy male presented with left upper-quadrant and shoulder pain without reported trauma. Computed-tomography (CT) imaging revealed splenomegaly, multiple splenic cystic lesions, and free intraperitoneal blood. A laparoscopic splenectomy, complicated by a pancreatic leak that was managed with a drain, was performed. The patient was discharged on postoperative day three and was well at 37 months follow-up. A 78-year-old male with splenomegaly and chronic anemia on warfarin for atrial fibrillation presented in shock with a distended abdomen after falling from a standing height. The patient was resuscitated with two units of packed red blood cells and underwent emergent abdominal exploration. The spleen was ruptured. An open splenectomy was performed and four liters of intraperitoneal blood were evacuated. Pathology confirmed splenic peliosis and historic diffuse large B-cell lymphoma. The patient had an excellent response to chemotherapy but died 12 years later. CLINICAL DISCUSSION: Splenic peliosis is a rare vascular phenomenon of unclear etiology. Several toxic and pharmaceutical agents have been associated with spontaneous splenic rupture in patients with peliosis. There are also a number of reported patients who were noted to have hematologic disorders, suggestive of a potential association to the pathophysiology of peliosis. CONCLUSION: Based on our clinical experience and focused literature review, it appears likely that there is a relationship between splenic peliosis and hematologic malignancy.

Simulation Training in a Lower Middle-Income Country: Supporting a New Center and Developing Low-Cost Models for Critical Skill Acquisition.

INTRODUCTION:  There is a demand for surgical simulation training to be made accessible in low-resource countries. We conducted a pilot workshop at a new state-of-the-art simulation center and evaluated two novel low-cost surgical simulation models in a lower middle-income country (LMIC). METHODS: A hands-on workshop to train local educators about simulation training was held at a new simulation center. Participant surveys were analyzed following the "training-the-trainer" workshop. Low-cost, hybrid-fidelity pericardiocentesis and thoracic cavity simulation training models were created using locally available materials. These models recreated the pertinent anatomy at a cost under 20 US dollars each. The models were used to train 109 postgraduate anesthesiology trainees during two hands-on medical education workshops. Participant surveys were collected and analyzed. RESULTS: Of the local educators who participated in the "training-the-trainer" workshop, 65% "agreed" and 35% "strongly agreed" with the claim that the simulations better prepared the trainees to teach the clinical scenarios. Additionally, 65% of local educators "agreed" and 35% "strongly agreed" that the simulations prepared them to navigate interprofessional care in those scenarios. The low-cost pericardiocentesis simulation was ranked as "good" or "outstanding" by 100% of survey respondents. The low-cost thoracostomy simulation was ranked as "good" or "outstanding" by 64% of survey respondents. Both the pericardiocentesis and thoracostomy simulators were valued for their low-cost design, the recreation of essential anatomy, and immersive design elements. CONCLUSION: Our team successfully implemented novel simulators for skill training in an LMIC by working in close collaboration with local experts, with the advancement of local simulation instruction practices. Collaboration is key to increasing access to surgical simulations, particularly in low- to middle-income countries.

Identification and molecular characterization of two recurrent missense mutations in the RS1 gene in two families with X-linked retinoschisis from North India.

X-linked retinoschisis (XLR) is a rare medical condition that involves in the splitting of neurosensory layers and the impairment of vision in the retina. In majority of the XLR cases, pathogenic variants in Retinoschisin 1 (RS1) gene have been implicated in males with an early age of onset during early childhood. In the present study, we have recruited two North Indian families having multiple affected male members, who were diagnosed with XLR. The entire protein-coding region of RS1 was screened by PCR-Sanger sequencing and two recurrent pathogenic variants (p.I81N and p.R102Q) were unraveled. The in vitro study of these variants demonstrated the aggregation of mutant RS1 within the endoplasmic reticulum. Furthermore, mutant forms of this protein showed significant intracellular retention, which was evident by the absence of retinoschisin protein fractions in the extracellular media. These inferences were also supported by extensive bioinformatics analysis of the mutants, which showed dramatic conformational changes in the local structure of retinoschisin. Thus, our study suggests that the identified pathogenic variants interfere with proper protein folding, leading to anomalous structural changes ultimately resulting in intracellular retention of retinoschisin within the retina.

Cellular Senescence, Inflammation, and Cancer in the Gastrointestinal Tract.

Due to modern medical advancements, greater proportions of the population will continue to age with longer life spans. Increased life span, however, does not always correlate with improved health span, and may result in an increase in aging-related diseases and disorders. These diseases are often attributed to cellular senescence, in which cells become disengaged from the cell cycle and inert to cell death. These cells are characterized by a proinflammatory secretome. The proinflammatory senescence-associated secretory phenotype, although part of a natural function intended to prevent further DNA damage, creates a microenvironment suited to tumor progression. This microenvironment is most evident in the gastrointestinal tract (GI), where a combination of bacterial infections, senescent cells, and inflammatory proteins can lead to oncogenesis. Thus, it is important to find potential senescence biomarkers as targets of novel therapies for GI diseases and disorders including cancers. However, finding therapeutic targets in the GI microenvironment to reduce the risk of GI tumor onset may also be of value. This review summarizes the effects of cellular senescence on GI aging, inflammation, and cancers, and aims to improve our understanding of these processes with a goal of enhancing future therapy.

It Is Not Only the Meniscus That Flips-A Case of TFCC Tear with a Flipped Fragment in the Distal Radioulnar Joint.

Acute wrist injuries with ongoing ulnar-sided wrist pain warrant a magnetic resonance imaging (MRI) to diagnose ligamentous injuries. Triangular fibrocartilage complex (TFCC) tears have been classified and described in the literature but complex tear patterns have limited representation. Bucket-handle tears of the TFCC represent only 0.5% of TFCC tears and have recently been identified, posing a diagnostic and management challenge. Preoperative diagnosis is possible with MRI and necessary for optimal and early surgical management. The authors describe a unique case of a flipped tear of the central disc of the TFCC, where the fragment was flipped into the distal radioulnar joint, a site hidden during routine arthroscopy.

An unbiased proteomics approach to identify the senescence-associated secretory phenotype of human bone marrow-derived mesenchymal stem cells.

Mesenchymal stem cells (MSCs) derived from bone marrow can support skeletal tissue repair and regeneration owing to their self-renewing capacity, differentiation ability, and trophic functions. Bone marrow-derived MSCs undergo dramatic changes with aging, including the senescence-associated secretory phenotype (SASP) which may largely contribute to age-related changes in bone tissue leading to osteoporosis. A mass spectrometry-based proteomics approach was used to investigate the MSC SASP. Replicative senescence was achieved by exhaustive in vitro sub-cultivation and confirmed by standard proliferation criteria. Conditioned media from non-senescent and senescent MSCs underwent mass spectrometry. Proteomics and bioinformatics analyses enabled the identification of 95 proteins expressed uniquely in senescent MSCs. Protein ontology analysis revealed the enrichment of proteins linked to the extracellular matrix, exosomes, cell adhesion, and calcium ion binding. The proteomic analysis was independently validated by taking ten identified proteins with relevance to bone aging and confirming their increased abundance in conditioned media from replicatively senescent versus non-senescent MSCs (ACTα2, LTF, SOD1, IL-6, LTBP2, PXDN, SERPINE 1, COL1α1, THBS1, OPG). These target proteins were used to further investigate changes in the MSC SASP profile in response to other inducers of senescence, ionizing radiation (IR) and H2O2. Similar secreted protein expression profiles with replicatively senescent cells were seen with H2O2 treatment except for LTF and PXDN, which were increased by IR treatment. With both IR and H2O2 treatment there was a decrease in THBS1. In vivo investigation of these secreted proteins with aging was shown by significant changes in the abundance of OPG, COL1α1, IL-6, ACTα2, SERPINE 1, and THBS1 in the plasma of aged rats. This unbiased, comprehensive analysis of the changes in the MSC secretome with senescence defines the unique protein signature of the SASP in these cells and provides a better understanding of the aging bone microenvironment.

Use of calcaneal plates in the treatment of posterior pelvic ring injuries and displaced iliac blade fractures- A case series.

Introduction: The operative fixation of pelvic ring injuries and associated acetabulum fractures presents a challenging scenario to most of the orthopaedic trauma surgeons. Current development of anatomically contoured reconstruction (ACR) plates gained popularity in fixing complex pelvic ring fractures. This study was done to assess the functional and radiological outcomes using of lateral wall stainless steel (LWSS) calcaneal plates in posterior pelvic ring injuries and displaced iliac blade fractures. Materials and methods: Retrospectively selected eight cases of pelvic ring injuries planned for fixing posterior pelvic instability and iliac blade fractures using LWSS plates. Mean follow-up was 18 months (Range 12-26 months). Results: Average time for radiological bony union achieved in 18 weeks (Range 13-22). Seven patients returned to their normal work. Average Majeed score was 60 (Range 50-68). Mean duration of surgery was 160 min (Range 120-200). Conclusion: This technique can be routinely used as supplementary fixation for posterior pelvic ring instability and iliac blade fractures. LWSS calcaneal plates showed no screw breakage or implant failure. Further this technique was cost effective in developing countries with limited resources.

Optimization of the frying process in relation to quality characteristics of Khaja (A traditional sweet).

The present study was focused on the optimization of process parameters and quality characterization of Khaja. A full factorial design 53 was applied using different levels of fat proportions (5-25%), frying temperature (160-200 °C), and frying time (1-5 min). The response optimizer function in Minitab 18 software was used to select five samples with the highest desirability which were then subjected to sensory analysis. The lightness of the samples decreased significantly (P ˂ 0.05) from 68.59 to 43.33 whereas, redness increased significantly (P ˂ 0.05) from 0.26 to 11.48 with increasing levels of all independent variables. Water activity and moisture content of the samples decreased significantly (P ˂ 0.05) from 0.75 to 0.21 and 14.41-1.40%wb respectively, whereas total fat content increased significantly (P ˂ 0.05) from 25.05 to 45.7% with increasing levels of independent variables. The hardness of the samples significantly (P ˂ 0.05) varied from 60.45 to 7.69 N. The sensory analysis revealed that the sample with 20% fat proportion, fried at 180 °C for 4 min, scored maximum in overall acceptability. The microstructural images revealed the structural damage and formation of pores in fried samples. The fatty acid analysis showed higher saturated fatty acids in market samples than in optimized samples. The results of the study concluded that fat proportion and frying parameters (temperature and time) are crucial for a better understanding of the deep-frying process of Khaja in order to achieve good quality. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-022-05509-x.

Kneeling Stress Radiography: A Forgotten Yet Dependable Tool for Postero-lateral Knee Instability.

Introduction: Diagnosing postero-lateral knee instability is a challenge from both clinical and radiologic perspective and can lead to significant morbidity if left untreated. Delayed diagnosis leads to a more demanding surgery and prolonged rehabilitation for the patient. Kneeling stress radiograph is a lost art but remains invaluable in the assessment of postero-lateral knee instability. Methods: This prospective observational study is aimed at re-exploring the undeniable utility of this forgotten tool in early diagnosis of posterolateral knee instability and identifying the mean posterior tibial translation distance (PTTD) and also assessing side to side difference (SSD) between the injured and the contralateral normal knee. Results: Total 27 patients were included in the study, with males being 4.4 times more commonly injured as compared to females. The most common mode of injury was motor vehicle accident (MVA). Out of 27 patients, 11 had isolated PCL (posterior cruciate ligament) injury while the rest had PLC (posterolateral corner) involvement. The mean SSD of PTTD was 8.79 mm in patient with isolated PCL. This was increased by 1.65 times (14.52 mm) in patients with co-existing PLC involvement. Conclusion: Stress radiography is an indelible tool and serves as an adjunct to MRI imaging. It is not a substitute for clinical assessment but assists in early diagnosis and management, facilitating surgical planning and furnishing objective evidence of PCL/PLC functionality which is not possible with any other imaging modality.

Molar Tooth in the Knee - A Case of Simultaneous Medial and Lateral Bucket Handle Tear with Arthroscopic Correlation and a Review of Literature.

Introduction: Simultaneous bucket handle tear of both lateral and medial menisci is a rarely encountered entity. MR imaging helps in pre-operative diagnosis for optimal operative planning. However, as this condition is not seen in routine practice, awareness of various imaging signs is essential to identify this condition. Few signs on coronal and sagittal images have been described in the literature but none so far on axial images. Case Presentation: We propose a novel "molar tooth sign" in the knee on axial MRI images, in which we identified in the case of a young male with recurrent knee locking after a fall from height. Conclusion: Different modes of injury can lead to different patterns of meniscal and ligament tears. Having an allied sign which is, furthermore, easy to imagine will help, not only the radiologists but also the surgeons, to identify rare types of meniscal tears similar to the index case.

Targeted clearance of p21- but not p16-positive senescent cells prevents radiation-induced osteoporosis and increased marrow adiposity.

Cellular senescence, which is a major cause of tissue dysfunction with aging and multiple other conditions, is known to be triggered by p16Ink4a or p21Cip1 , but the relative contributions of each pathway toward inducing senescence are unclear. Here, we directly addressed this issue by first developing and validating a p21-ATTAC mouse with the p21Cip1 promoter driving a "suicide" transgene encoding an inducible caspase-8 which, upon induction, selectively kills p21Cip1 -expressing senescent cells. Next, we used the p21-ATTAC mouse and the established p16-INK-ATTAC mouse to directly compare the contributions of p21Cip1 versus p16Ink4a in driving cellular senescence in a condition where a tissue phenotype (bone loss and increased marrow adiposity) is clearly driven by cellular senescence-specifically, radiation-induced osteoporosis. Using RNA in situ hybridization, we confirmed the reduction in radiation-induced p21Cip1 - or p16Ink4a -driven transcripts following senescent cell clearance in both models. However, only clearance of p21Cip1 +, but not p16Ink4a +, senescent cells prevented both radiation-induced osteoporosis and increased marrow adiposity. Reduction in senescent cells with dysfunctional telomeres following clearance of p21Cip1 +, but not p16Ink4a +, senescent cells also reduced several of the radiation-induced pro-inflammatory senescence-associated secretory phenotype factors. Thus, by directly comparing senescent cell clearance using two parallel genetic models, we demonstrate that radiation-induced osteoporosis is driven predominantly by p21Cip1 - rather than p16Ink4a -mediated cellular senescence. Further, this approach can be used to dissect the contributions of these pathways in other senescence-associated conditions, including aging across tissues.

Bone Marrow Adiposity in Models of Radiation- and Aging-Related Bone Loss Is Dependent on Cellular Senescence.

Oxidative stress-induced reactive oxygen species, DNA damage, apoptosis, and cellular senescence have been associated with reduced osteoprogenitors in a reciprocal fashion to bone marrow adipocyte tissue (BMAT); however, a direct (causal) link between cellular senescence and BMAT is still elusive. Accumulation of senescent cells occur in naturally aged and in focally radiated bone tissue, but despite amelioration of age- and radiation-associated bone loss after senescent cell clearance, molecular events that precede BMAT accrual are largely unknown. Here we show by RNA-Sequencing data that BMAT-related genes were the most upregulated gene subset in radiated bones of C57BL/6 mice. Using focal radiation as a model to understand age-associated changes in bone, we performed a longitudinal assessment of cellular senescence and BMAT. Using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), RNA in situ hybridization of p21 transcripts and histological assessment of telomere dysfunction as a marker of senescence, we observed an increase in senescent cell burden of bone cells from day 1 postradiation, without the presence of BMAT. BMAT was significantly elevated in radiated bones at day 7, confirming the qRT-PCR data in which most BMAT-related genes were elevated by day 7, and the trend continued until day 42 postradiation. Similarly, elevation in BMAT-related genes was observed in bones of aged mice. The senolytic cocktail of Dasatinib (D) plus Quercetin (Q) (ie, D + Q), which clears senescent cells, reduced BMAT in aged and radiated bones. MicroRNAs (miRNAs or miRs) linked with senescence marker p21 were downregulated in radiated and aged bones, whereas miR-27a, a miR that is associated with increased BMAT, was elevated both in radiated and aged bones. D + Q downregulated miR-27a in radiated bones at 42 days postradiation. Overall, our study provides evidence that BMAT occurrence in oxidatively stressed bone environments, such as radiation and aging, is induced following a common pathway and is dependent on the presence of senescent cells. © 2022 American Society for Bone and Mineral Research (ASBMR).

Aging of enteric neuromuscular systems in gastrointestinal tract.

BACKGROUND: Aging is a complex biological process and associated with a progressive decline in functions of most organs including the gastrointestinal (GI) tract. Age-related GI motor disorders/dysfunctions include esophageal reflux, dysphagia, constipation, fecal incontinence, reduced compliance, and accommodation. Although the incidence and severity of these diseases and conditions increase with age, they are often underestimated due in part to nonspecific and variable symptoms and lack of sufficient medical attention. They negatively affect quality of life and predispose the elderly to other diseases, sarcopenia, and frailty. The mechanisms underlying aging-associated GI dysfunctions remain unclear, and there is limited data examining the effect of aging on GI motor functions. Many studies on aging-associated changes to cells within the tunica muscularis including enteric neurons, smooth muscles, and interstitial cells have proposed that cell loss and/or molecular changes may be involved in the pathogenesis of age-related GI motor disorders/dysfunctions. There is also evidence that the aging contributes to phenotypic changes in innate immune cells, which are physically and functionally linked to other cells in the tunica muscularis and can alter GI (patho) physiology. However, various patterns of changes have been reported, some of which are contradictory, indicating a need for additional work in this area. PURPOSE: Although GI infection due to intestinal bacterial overgrowth, bleeding, and cancers are also important and common problems in the elderly patients, this mini-review focuses on data obtained from enteric neuromuscular aging research with the goal of better understanding the cellular and molecular mechanisms of enteric neuromuscular aging to enhance future therapy.