Mesenchymal stromal cells as conductors of adipose tissue remodeling.

Adipose tissue exhibits a remarkable capacity to expand, contract, and remodel in response to changes in physiological and environmental conditions. Here, we describe recent advances in our understanding of how functionally distinct tissue-resident mesenchymal stromal cell subpopulations orchestrate several aspects of physiological and pathophysiological adipose tissue remodeling, with a particular focus on the adaptations that occur in response to changes in energy surplus and environmental temperature. The study of adipose tissue remodeling provides a vehicle to understand the functional diversity of stromal cells and offers a lens through which several generalizable aspects of tissue reorganization can be readily observed.

Cold-responsive adipocyte progenitors couple adrenergic signaling to immune cell activation to promote beige adipocyte accrual.

The full array of cold-responsive cell types within white adipose tissue that drive thermogenic beige adipocyte biogenesis remains undefined. We demonstrate that acute cold challenge elicits striking transcriptomic changes specifically within DPP4+ PDGFRß+ adipocyte precursor cells, including a ß-adrenergic receptor CREB-mediated induction in the expression of the prothermogenic cytokine, Il33 Doxycycline-inducible deletion of Il33 in PDGFRß+ cells at the onset of cold exposure attenuates ILC2 accumulation and beige adipocyte accrual. These studies highlight the multifaceted roles for adipocyte progenitors and the ability of select mesenchymal subpopulations to relay neuronal signals to tissue-resident immune cells in order to regulate tissue plasticity.

ZFP423 controls EBF2 coactivator recruitment and PPARγ occupancy to determine the thermogenic plasticity of adipocytes.

Energy-storing white adipocytes maintain their identity by suppressing the energy-burning thermogenic gene program of brown and beige adipocytes. Here, we reveal that the protein-protein interaction between the transcriptional coregulator ZFP423 and brown fat determination factor EBF2 is essential for restraining the thermogenic phenotype of white adipose tissue (WAT). Disruption of the ZFP423-EBF2 protein interaction through CRISPR-Cas9 gene editing triggers widespread "browning" of WAT in adult mice. Mechanistically, ZFP423 recruits the NuRD corepressor complex to EBF2-bound thermogenic gene enhancers. Loss of adipocyte Zfp423 induces an EBF2 NuRD-to-BAF coregulator switch and a shift in PPARγ occupancy to thermogenic genes. This shift in PPARγ occupancy increases the antidiabetic efficacy of the PPARγ agonist rosiglitazone in obesity while diminishing the unwanted weight-gaining effect of the drug. These data indicate that ZFP423 controls EBF2 coactivator recruitment and PPARγ occupancy to determine the thermogenic plasticity of adipocytes and highlight the potential of therapeutically targeting transcriptional brakes to induce beige adipocyte biogenesis in obesity.

Functional Interplay between Histone H2B ADP-Ribosylation and Phosphorylation Controls Adipogenesis.

Although ADP-ribosylation of histones by PARP-1 has been linked to genotoxic stress responses, its role in physiological processes and gene expression has remained elusive. We found that NAD+-dependent ADP-ribosylation of histone H2B-Glu35 by small nucleolar RNA (snoRNA)-activated PARP-1 inhibits AMP kinase-mediated phosphorylation of adjacent H2B-Ser36, which is required for the proadipogenic gene expression program. The activity of PARP-1 on H2B requires NMNAT-1, a nuclear NAD+ synthase, which directs PARP-1 catalytic activity to Glu and Asp residues. ADP-ribosylation of Glu35 and the subsequent reduction of H2B-Ser36 phosphorylation inhibits the differentiation of adipocyte precursors in cultured cells. Parp1 knockout in preadipocytes in a mouse lineage-tracing genetic model increases adipogenesis, leading to obesity. Collectively, our results demonstrate a functional interplay between H2B-Glu35 ADP-ribosylation and H2B-Ser36 phosphorylation that controls adipogenesis.

TRPV4 is a regulator of adipose oxidative metabolism, inflammation, and energy homeostasis.

PGC1α is a key transcriptional coregulator of oxidative metabolism and thermogenesis. Through a high-throughput chemical screen, we found that molecules antagonizing the TRPVs (transient receptor potential vanilloid), a family of ion channels, induced PGC1α expression in adipocytes. In particular, TRPV4 negatively regulated the expression of PGC1α, UCP1, and cellular respiration. Additionally, it potently controlled the expression of multiple proinflammatory genes involved in the development of insulin resistance. Mice with a null mutation for TRPV4 or wild-type mice treated with a TRPV4 antagonist showed elevated thermogenesis in adipose tissues and were protected from diet-induced obesity, adipose inflammation, and insulin resistance. This role of TRPV4 as a cell-autonomous mediator for both the thermogenic and proinflammatory programs in adipocytes could offer a target for treating obesity and related metabolic diseases.

C/EBPß controls exercise-induced cardiac growth and protects against pathological cardiac remodeling.

The heart has the ability to grow in size in response to exercise, but little is known about the transcriptional mechanisms underlying physiological hypertrophy. Adult cardiomyocytes have also recently been proven to hold the potential for proliferation, a process that could be of great importance for regenerative medicine. Using a unique RT-PCR-based screen against all transcriptional components, we showed that C/EBPß was downregulated with exercise, whereas the expression of CITED4 was increased. Reduction of C/EBPß in vitro and in vivo resulted in a phenocopy of endurance exercise with cardiomyocyte hypertrophy and proliferation. This proliferation was mediated, at least in part, by the increased CITED4. Importantly, mice with reduced cardiac C/EBPß levels displayed substantial resistance to cardiac failure upon pressure overload. These data indicate that C/EBPß represses cardiomyocyte growth and proliferation in the adult mammalian heart and that reduction in C/EBPß is a central signal in physiologic hypertrophy and proliferation.

PARP-1 Controls the Adipogenic Transcriptional Program by PARylating C/EBPß and Modulating Its Transcriptional Activity.

Poly(ADP-ribosyl)ation (PARylation) is a post-translational modification of proteins mediated by PARP family members, such as PARP-1. Although PARylation has been studied extensively, few examples of definitive biological roles for site-specific PARylation have been reported. Here we show that C/EBPß, a key pro-adipogenic transcription factor, is PARylated by PARP-1 on three amino acids in a conserved regulatory domain. PARylation at these sites inhibits C/EBPß's DNA binding and transcriptional activities and attenuates adipogenesis in various genetic and cell-based models. Interestingly, PARP-1 catalytic activity drops precipitously during the first 48 hr of differentiation, corresponding to a release of C/EBPß from PARylation-mediated inhibition. This promotes the binding of C/EBPß at enhancers controlling the expression of adipogenic target genes and continued differentiation. Depletion or chemical inhibition of PARP-1, or mutation of the PARylation sites on C/EBPß, enhances these early adipogenic events. Collectively, our results provide a clear example of how site-specific PARylation drives biological outcomes.

Sorting out adipocyte precursors and their role in physiology and disease.

The ability to maintain and expand the pool of adipocytes in adults is integral to the regulation of energy balance, tissue/stem cell homeostasis, and disease pathogenesis. For decades, our knowledge of adipocyte precursors has relied on cellular models. The identity of native adipocyte precursors has remained unclear. Recent studies have identified distinct adipocyte precursor populations that are physiologically regulated and contribute to the development, maintenance, and expansion of adipocyte pools in mice. With new tools available, the properties of adipocyte precursors can now be defined, and the regulation and function of adipose plasticity in development and physiology can be explored.

Regulation of cold-induced thermogenesis by the RNA binding protein FAM195A.

Homeothermic vertebrates produce heat in cold environments through thermogenesis, in which brown adipose tissue (BAT) increases mitochondrial oxidation along with uncoupling of the electron transport chain and activation of uncoupling protein 1 (UCP1). Although the transcription factors regulating the expression of UCP1 and nutrient oxidation genes have been extensively studied, only a few other proteins essential for BAT function have been identified. We describe the discovery of FAM195A, a BAT-enriched RNA binding protein, which is required for cold-dependent thermogenesis in mice. FAM195A knockout (KO) mice display whitening of BAT and an inability to thermoregulate. In BAT of FAM195A KO mice, enzymes involved in branched-chain amino acid (BCAA) metabolism are down-regulated, impairing their response to cold. Knockdown of FAM195A in brown adipocytes in vitro also impairs expression of leucine oxidation enzymes, revealing FAM195A to be a regulator of BCAA metabolism and a potential target for metabolic disorders.

Navigating parental attitudes on childhood vaccination in Jordan: a cross-sectional study.

This study investigated parental attitudes toward childhood vaccination in Jordan, focusing on acceptance, concerns, and perceptions. A cross-sectional survey conducted from January to February 2024 included 939 parents. Findings indicated that 85.4% (n = 802) of respondents received the COVID-19 vaccine, while only 25% (n = 229) vaccinated their children. Concerns regarding vaccine safety and efficacy were prevalent, with 63.9% (n = 600) expressing worries about side effects and 46.9% (n = 440) trusting immunization programs. Post-pandemic, 34% (n = 319) reported a more negative attitude. Logistic regression showed parents not vaccinating their children against COVID-19 were significantly less likely to exhibit positive attitudes toward childhood vaccination (OR = 0.412, p < 0.001). Older participants were more inclined toward negativity post-pandemic (OR = 1.031, p = 0.007). In conclusion, parental attitudes shifted post-COVID-19, reflecting hesitancy and decreased trust. Addressing concerns and restoring confidence are crucial, especially for children's health. Education through healthcare providers and dispelling social media misinformation are essential. Implementing strategies to enhance post-pandemic vaccine acceptance is imperative for preventing outbreaks of vaccine-preventable diseases.

Morpho-molecular characterisation of two new and two previously reported species of Acanthogyrus (Acanthogyrus: Quadrigyridae) from freshwater fishes in India.

Of the total 47 species in the subgenus Acanthosentis, 43 have been reported from the freshwater fishes of Asia. Amin et al. (2017) provided a key to the 23 species of the genus Acanthogyrus reported from the Indian subcontinent. The present study reports two new species: Acanthogyrus bispinosa n. sp. and A. garciai n. sp. from Cirrhinus mrigala Hamilton and Labeo calbasu Hamilton, respectively, and two previously described species: A. golvani Gupta and Jain, 1980 and A. hereterospinus Khan and Bilqees, 1990 from L. rohita Hamilton and L. catla Hamilton, respectively. A. bispinosa n. sp. comprises 3 circles of 6 proboscis hooks each. Trunk spines in A. bispinosa n. sp are divided into two groups: anterior and posterior separated by unarmed region, which has not been previously reported in the subgenus. Anterior spines are present in 7-8 and 7-10 circles in females and males, respectively, whereas posterior spines are in 23-28 and 31-38 circles in males and females, respectively. A. garciai n. sp. comprises 3 circles of 6-8 hooks each and a single set of trunk spines is present in A. garciai n. sp., comprising 35-42 and 25-45 circles in males and females, respectively. All four species were also characterised based on the 18S, 28S, and ITS1-5.8S-ITS2 rRNA molecular markers. The Bayesian inference tree generated based on these markers showed distinct identities of all the species, with a significant molecular divergence, ranging from 3.2 to 53.6%.

Frequency of Low Cardiac Output Syndrome Following on Pump Coronary Artery Bypass Grafting Surgery and it's Association with Degree of Pre-operative Left Ventricular Dysfunction.

Background Low cardiac output syndrome (LCOS) is a serious complication after coronary artery bypass grafting (CABG) surgery. It is associated with 10 times to 17 times increase in mortality and markedly increase morbidity. Objective To find out the frequency of Low cardiac output syndrome following on pump coronary artery bypass grafting surgery, to determine the association of Low cardiac output syndrome with degree of pre-operative left ventricular dysfunction and to compare in hospital outcomes of coronary bypass surgery with and without low cardiac output syndrome. Method This prospective, descriptive study enrolled 200 patients who underwent on pump coronary artery bypass grafting surgery using antegrade St Thomas blood cardioplegia. Pre-operatively grouped into two groups consisting Group A of 100 patients with pre-operative left ventricular ejection fraction (LVEF) ≥ 40% and group B of 100 patients with pre-operative left ventricular ejection fraction (LVEF) < 40%. Post-operatively frequency of low cardiac output syndrome was compared between the groups and in-hospital outcomes were studied. Result The mean age of the patients in the study was 53.50±7.57 years. Male to female ratio was 1.8:1. Results showed overall frequency of low cardiac output syndrome was 21.5%. The frequency of LCOS was 15 vs 28% (p - 0.038) in patients with preoperative LV EF ≥ 40% and < 40% respectively. The outcomes of coronary artery bypass grafting surgery were stroke (3.82 vs. 30.23%, p - 0.001), acute kidney injury (5.09 vs. 23.25%, p - 0.001), respiratory failure (6.36 vs. 34.88%, p - 0.001), ICU stay days (4.75 ± 1.28 vs. 7.44 ± 4.66, p - 0.018), hospital stay days (9.56 ± 2.40 vs. 15.22 ± 3.89, p - 0.001) and mortality (4.45 vs. 32.55%, p - 0.001) in patients without and with low cardiac output syndrome respectively. Conclusion The frequency of low cardiac output syndrome following coronary artery bypass surgery is 21.5%. Left ventricular dysfunction pre-operatively is associated with high frequency of low cardiac output syndrome following surgery. There is significantly poor outcome of coronary artery bypass surgery with low cardiac output syndrome in terms of stroke, respiratory failure, acute kidney injury, mortality and significant ICU stay, hospital stay in compare to patients without low cardiac output syndrome.

Gas-phase synthesis of racemic helicenes and their potential role in the enantiomeric enrichment of sugars and amino acids in meteorites.

The molecular origins of homochirality on Earth is not understood well, particularly how enantiomerically enriched molecules of astrobiological significance like sugars and amino acids might have been synthesized on icy grains in space preceding their delivery to Earth. Polycyclic aromatic hydrocarbons (PAHs) identified in carbonaceous chondrites could have been processed in molecular clouds by circularly polarized light prior to the depletion of enantiomerically enriched helicenes onto carbonaceous grains resulting in chiral islands. However, the fundamental low temperature reaction mechanisms leading to racemic helicenes are still unknown. Here, by exploiting synchrotron based molecular beam photoionization mass spectrometry combined with electronic structure calculations, we provide compelling testimony on barrierless, low temperature pathways leading to racemates of [5] and [6]helicene. Astrochemical modeling advocates that gas-phase reactions in molecular clouds lead to racemates of helicenes suggesting a pathway for future astronomical observation and providing a fundamental understanding for the origin of homochirality on early Earth.

Hyperoxia After Return of Spontaneous Circulation in Cardiac Arrest Patients.

Current guidelines emphasize the use of 100% oxygen during cardiopulmonary resuscitation after cardiac arrest. When patients are ventilated for variable periods after return of spontaneous circulation (ROSC), hyperoxia causes increased morbidity and mortality by overproduction of reactive oxygen species. Various patient, volunteer, and animal studies have shown the harmful effects of hyperoxia. This mini-review article aims to expand the potential clinical spectrum of hyperoxia on individual organ systems leading to organ dysfunction. A framework to achieve and maintain normoxia after ROSC is proposed. Despite the harmful considerations of hyperoxia in critically ill patients, additional safety studies including dose-effect, level and onset of the reactive oxygen species effect, and safe hyperoxia applicability period after ROSC, need to be performed in various animal and human models to further elucidate the role of oxygen therapy after cardiac arrest.

Echocardiography and Management for Cardiac Trauma.

Trauma is the number one cause of death among Americans between the ages of 1 and 46, costing >$670 billion a year. Blunt and penetrating trauma can lead to cardiac and aortic injuries, with the incidence of death varying upon the location of the damage. Among those who reach the hospital alive, many may survive if the hemorrhage and cardiovascular injuries are diagnosed and treated adequately in a timely fashion. Although echocardiography often is underused in the setting of cardiac trauma, it offers significant diagnosis and treatment potential because it is accessible in most settings, safe, relatively noninvasive, and can provide rapid and accurate trauma assessment in the hands of trained providers. This review article aims to analyze the pathophysiology of cardiac injuries in patients with trauma and the role of echocardiography for the accurate diagnosis of cardiac injury in trauma. This review, additionally, will offer a patient-centered, team-based, early management plan with a treatment algorithm to help improve the quality of care among these patients with cardiac trauma.

Gas-phase synthesis of corannulene - a molecular building block of fullerenes.

Fullerenes (C60, C70) detected in planetary nebulae and carbonaceous chondrites have been implicated to play a key role in the astrochemical evolution of the interstellar medium. However, the formation mechanism of even their simplest molecular building block-the corannulene molecule (C20H10)-has remained elusive. Here we demonstrate via a combined molecular beams and ab initio investigation that corannulene can be synthesized in the gas phase through the reactions of 7-fluoranthenyl (C16H9˙) and benzo[ghi]fluoranthen-5-yl (C18H9˙) radicals with acetylene (C2H2) mimicking conditions in carbon-rich circumstellar envelopes. This reaction sequence reveals a reaction class in which a polycyclic aromatic hydrocarbon (PAH) radical undergoes ring expansion while simultaneously forming an out-of-plane carbon backbone central to 3D nanostructures such as buckybowls and buckyballs. These fundamental reaction mechanisms are critical in facilitating an intimate understanding of the origin and evolution of the molecular universe and, in particular, of carbon in our galaxy.

Prevalence and predictors of polypharmacy in Jordanian hospitalised patients: A cross-sectional Study.

OBJECTIVES: This study aimed to evaluate the prevalence and predictors of polypharmacy in hospitalised patients in Jordan to help guide healthcare efforts in decreasing the burden on the healthcare system. METHODS: This cross-sectional study was conducted at the University of Jordan Hospital in Amman, Jordan. During the study period, a convenience sample of patients admitted to the internal medicine and surgical wards were approached to take part in this study. Following patients' recruitments, patients were interviewed and their medical files were reviewed to obtain demographic and clinical information regarding their medical conditions and their regular use of medicines. Then, the prevelence of patients with polypharmacy were identified, and factors predicting polypharmacy among them were determined. RESULTS: Among the 300 participants who agreed to participate in this study, females represented 45.3% of the recruited sample (n = 139), and around 48.0% (n = 144) of the study sample were elderly people (≥65 years old). Most of the recruited patients (n = 248, 82.7%) were found to use polypharmacy (≥ 5 medications). Hypertension was the most frequent medical condition among study participants (n = 240, 80.0%) followed by diabetes (n = 185, 61.7%). Results of logistic regression analysis showed that polypharmacy was only significantly affected by patients' age (OR = 2.149, P-value = .024) and monthly income (OR = 0.336, P-value = .009), while other factors were not associated with polypharmacy. Elderly patients (≥65 years) were found to have polypharmacy more significantly than non-elderly patients. Also, those with lower monthly income (<500 JD) were found to use lower polypharmacy compared with those with higher monthly income (>500 JD). CONCLUSION: The present study showed that polypharmacy is prevalent among patients in Jordan. While polypharmacy was not affected by smoking status, gender, BMI and educational level, it was significantly affected by monthly income and age. Further plans should be put in place to reduce polypharmacy, starting with effective pharmaceutical care services leading to treatment optimisation and ensuring desired treatment outcomes.

Knowledge and attitudes of pharmacists towards colorectal cancer health education in Jordan: A cross-sectional study.

AIMS OF THE STUDY: The purpose of this study was to assess pharmacists' knowledge and attitude towards early detection of colorectal cancer (CRC) in Jordan and to explore potential predictor variables of such knowledge and attitude. METHODS USED TO CONDUCT THE STUDY: An electronic, self-reported questionnaire was used to collect data about demographics, knowledge and attitude regarding early detection of CRC. Both content and face validity were tested in a panel of experts. The participants' responses were analysed using descriptive statistics and multiple linear regressions. RESULTS OF THE STUDY: The 352 pharmacists (78% females, 94% Jordanian) had a median age of 28 years and graduated mostly (83%) from public universities. Surprisingly, 90% were not able to identify carcinoembryonic antigen (CEA) as a non-accurate diagnostic method and almost one-third did not identify the correct screening tests. On a scale of 5, the majority of participants (59%) had moderate knowledge scores (3 or 4) in case scenarios. The median knowledge Percent of Maximum Possible (POMP) score was 67% and higher scores were associated with more years since graduation, pharmacists with MSc degree and higher, working in urban areas, studying oncology course and received oncology training (P < .05). Most participants showed a positive attitude towards early detection of CRC (median attitude POMP score was 78%). However, none of the analysed variables predicted their level of attitude. CONCLUSIONS DRAWN FROM THE STUDY AND CLINICAL IMPLICATIONS: Although the majority of pharmacists demonstrated a positive attitude towards early detection of CRC, their knowledge was inadequate. The study highlighted the importance of optimising the education programmes to improve the pharmacists' knowledge about CRC early detection and preparing the pharmacists for participating in future national screening initiatives.

Caesarean section delivery from maternal perspective: An exploratory study in Jordan.

AIMS OF THE STUDY: This study aims to determine females' views, experiences and attitudes regarding the caesarean section (CS) and to explore the factors that increase the prevalence of CS in Jordan. DESIGN: This is a cross-sectional study using a questionnaire that was distributed electronically through social media websites. Study participants included 1005 females with a history of at least one CS. Awareness, experiences about CS, complications and reasons for performing CS were investigated. SETTINGS: The participants were recruited from all Jordan cities by social media and emails. FINDINGS: Most of the respondents stated that the source of their knowledge about CS was from the internet (36.2%) followed by family and friends (31.6%). The majority of respondents were satisfied with their CS experience (72.8%). More than half of the participants (56.9%) reported that CS carries no risk for infants. About 53% of respondents stated that the most common reason leading women to choose to give birth via CS is the fear of labour pain. However, the majority of the respondents disagree with performing CS under maternal request (59.2%). CONCLUSIONS AND IMPLICATIONS: This study indicated that Jordanian females do not have reliable sources of information about CS. This leads to lower awareness of CS and its complications, and, as expected, CS is more likely to be performed by privately insured women.

Community pharmacists' preparedness and responses to COVID-19 pandemic: A multinational study.

BACKGROUND: Community pharmacists play a pivotal role in healthcare worldwide. Their role became more critical during the COVID-19 pandemic. This study aims to investigate the community pharmacists' preparedness and responses to the COVID-19 pandemic and how efficiently they were prepared to contain and prevent the spread of infection. METHODS: An online questionnaire was distributed to community pharmacists in Saudi Arabia, Lebanon, and Jordan through social media platforms. A scoring system was developed to measure their level of adherence to the preventive measures of the global infection. RESULTS: The total included responses were 800. Around 44% of the pharmacists reported spending less than 15 min/d reading about COVID-19 updates. Although more than half of them were reviewing official sites, 73% of them were also retrieving information through non-official channels. Additionally, almost 35% of them were directly contacting customers without physical barriers, 81% reported encountering infected customers, and 12% wore the same facial masks for more than a day. Moreover, 58% of the pharmacies reported the absence of door signs requesting infected customers to declare the infection, 43% of the pharmacies were not limiting the number of simultaneous customers, and 70% were not measuring customers' temperatures prior to entry. Collectively, the mean total score of applied protective measures was 10.12 ± 2.77 (out of 17). CONCLUSION: The level of preparedness of the community pharmacies in these three Middle Eastern countries was not adequate for facing the COVID-19 pandemic. Health authorities in these countries should closely monitor their adherence to the protective guidelines.