A Breakdown in Cooperativity Leads to Cardiac Identity Crisis.

Using induced pluripotent stem cells, Ang et al. elucidate how a mutation in the transcription factor GATA4 causes congenital heart disease. They find that, although the recruitment of GATA4 to cardiac super-enhancers is retained, it no longer functions in partnership with another key transcription factor, leading to misexpression of non-cardiomyocyte genes.

The oxygen-rich postnatal environment induces cardiomyocyte cell-cycle arrest through DNA damage response.

The mammalian heart has a remarkable regenerative capacity for a short period of time after birth, after which the majority of cardiomyocytes permanently exit cell cycle. We sought to determine the primary postnatal event that results in cardiomyocyte cell-cycle arrest. We hypothesized that transition to the oxygen-rich postnatal environment is the upstream signal that results in cell-cycle arrest of cardiomyocytes. Here, we show that reactive oxygen species (ROS), oxidative DNA damage, and DNA damage response (DDR) markers significantly increase in the heart during the first postnatal week. Intriguingly, postnatal hypoxemia, ROS scavenging, or inhibition of DDR all prolong the postnatal proliferative window of cardiomyocytes, whereas hyperoxemia and ROS generators shorten it. These findings uncover a protective mechanism that mediates cardiomyocyte cell-cycle arrest in exchange for utilization of oxygen-dependent aerobic metabolism. Reduction of mitochondrial-dependent oxidative stress should be an important component of cardiomyocyte proliferation-based therapeutic approaches.

Metabolic switches during development and regeneration.

Metabolic switches are a crucial hallmark of cellular development and regeneration. In response to changes in their environment or physiological state, cells undergo coordinated metabolic switching that is necessary to execute biosynthetic demands of growth and repair. In this Review, we discuss how metabolic switches represent an evolutionarily conserved mechanism that orchestrates tissue development and regeneration, allowing cells to adapt rapidly to changing conditions during development and postnatally. We further explore the dynamic interplay between metabolism and how it is not only an output, but also a driver of cellular functions, such as cell proliferation and maturation. Finally, we underscore the epigenetic and cellular mechanisms by which metabolic switches mediate biosynthetic needs during development and regeneration, and how understanding these mechanisms is important for advancing our knowledge of tissue development and devising new strategies to promote tissue regeneration.

Asparagine Synthetase Marks a Distinct Dependency Threshold for Cardiomyocyte Dedifferentiation.

BACKGROUND: Adult mammalian cardiomyocytes have limited proliferative capacity, but in specifically induced contexts they traverse through cell-cycle reentry, offering the potential for heart regeneration. Endogenous cardiomyocyte proliferation is preceded by cardiomyocyte dedifferentiation (CMDD), wherein adult cardiomyocytes revert to a less matured state that is distinct from the classical myocardial fetal stress gene response associated with heart failure. However, very little is known about CMDD as a defined cardiomyocyte cell state in transition. METHODS: Here, we leveraged 2 models of in vitro cultured adult mouse cardiomyocytes and in vivo adeno-associated virus serotype 9 cardiomyocyte-targeted delivery of reprogramming factors (Oct4, Sox2, Klf4, and Myc) in adult mice to study CMDD. We profiled their transcriptomes using RNA sequencing, in combination with multiple published data sets, with the aim of identifying a common denominator for tracking CMDD. RESULTS: RNA sequencing and integrated analysis identified Asparagine Synthetase (Asns) as a unique molecular marker gene well correlated with CMDD, required for increased asparagine and also for distinct fluxes in other amino acids. Although Asns overexpression in Oct4, Sox2, Klf4, and Myc cardiomyocytes augmented hallmarks of CMDD, Asns deficiency led to defective regeneration in the neonatal mouse myocardial infarction model, increased cell death of cultured adult cardiomyocytes, and reduced cell cycle in Oct4, Sox2, Klf4, and Myc cardiomyocytes, at least in part through disrupting the mammalian target of rapamycin complex 1 pathway. CONCLUSIONS: We discovered a novel gene Asns as both a molecular marker and an essential mediator, marking a distinct threshold that appears in common for at least 4 models of CMDD, and revealing an Asns/mammalian target of rapamycin complex 1 axis dependency for dedifferentiating cardiomyocytes. Further study will be needed to extrapolate and assess its relevance to other cell state transitions as well as in heart regeneration.

mTORC1 regulates the metabolic switch of postnatal cardiomyocytes during regeneration.

The metabolic switch from glycolysis to fatty acid oxidation in postnatal cardiomyocytes contributes to the loss of the cardiac regenerative potential of the mammalian heart. However, the mechanisms that regulate this metabolic switch remain unclear. The protein kinase complex mechanistic target of rapamycin complex 1 (mTORC1) is a central signaling hub that regulates cellular metabolism and protein synthesis, yet its role during mammalian heart regeneration and postnatal metabolic maturation is undefined. Here, we use immunoblotting, rapamycin treatment, myocardial infarction, and global proteomics to define the role of mTORC1 in postnatal heart development and regeneration. Our results demonstrate that the activity of mTORC1 is dynamically regulated between the regenerating and the non-regenerating hearts. Acute inhibition of mTORC1 by rapamycin or everolimus reduces cardiomyocyte proliferation and inhibits neonatal heart regeneration following injury. Our quantitative proteomic analysis demonstrates that transient inhibition of mTORC1 during neonatal heart injury did not reduce protein synthesis, but rather shifts the cardiac proteome of the neonatal injured heart from glycolysis towards fatty acid oxidation. This indicates that mTORC1 inhibition following injury accelerates the postnatal metabolic switch, which promotes metabolic maturation and impedes cardiomyocyte proliferation and heart regeneration. Taken together, our results define an important role for mTORC1 in regulating postnatal cardiac metabolism and may represent a novel target to modulate cardiac metabolism and promote heart regeneration.

Treatment modalities and survival outcomes in prostate cancer parenchymal brain metastasis.

BACKGROUND: Prostate cancer (PCa) parenchymal brain metastases are uncommon and troubling observations in the course of the disease. Our study aims to evaluate the prevalence of brain metastases among PCa patients while reporting various therapeutic modalities, clinical features, and oncological outcomes. METHODS: We retrospectively identified 34 patients with parenchymal brain metastasis out of 4575 patients using a prospectively maintained database that contains clinicopathologic characteristics of PCa patients between January 2012 and December 2021. Based on the three treatment modalities used, the patients were divided into three groups: stereotactic radiosurgery (SRS), whole brain radiotherapy (WBRT), and systemic therapy alone. The Kaplan-Meier curve was used to calculate overall survival [OS] probability and the Cox proportional hazards regression model was used to compare between groups. RESULTS: At the time of brain metastasis diagnosis, the median age was 66 years, the median (interquartile range [IQR]) prostate-specific antigen (PSA) was 2.2 (0.1-26.6) ng/ml and the median (IQR) months from initial PCa diagnosis to brain metastasis development was 70.8 (27.6-100.9). The median (IQR) primary Gleason score was 8 (7-9) and over a median (IQR) follow-up time of 2.2 (1.2-16.5) months, 76.5% (n = 26) of the patients died. Thirteen (38.2%) patients had solitary lesion, whereas 21 (61.8%) had ≥2 lesions. The lesions were supratentorial in 19 (55.9%) patients, infratentorial in six (17.6%), and both sides in nine (26.5%). Among all 34 patients, 10 (29.4%) were treated with SRS, seven (20.6%) with WBRT, and 17 (50%) with systemic therapy alone. OS varied greatly between the three treatment modalities (log-rank test, p = 0.049). Those who were treated with SRS and WBRT had better OS compared with patients who were treated with systemic therapy alone (hazard ratio: 0.37, 95% confidence interval: 0.16-0.86, p = 0.022). CONCLUSIONS: In our single-institutional study, we confirmed that PCa brain metastasis is associated with poor survival outcomes and more advanced metastatic disease. Furthermore, we found that SRS and WBRT for brain metastasis in patients with recurrent PCa appear to be associated with improved OS as compared with systemic therapy alone and are likely secondary to selection bias.

L-2-hydroxyglutaric aciduria: a report of clinical, radiological, and genetic characteristics of two siblings from Egypt.

L-2-hydroxyglutaric aciduria (L-2-HGA) is a rare autosomal recessive disease characterized by elevated levels of hydroxyglutaric acid in the body fluids and brain with abnormal white matter. We present two siblings with psychomotor retardation and quadriparesis. Their brain imaging showed diffuse bilateral symmetrical involvement of the cerebral cortex, white matter, basal ganglia and cerebellum. The whole exome sequence studies revealed a homozygous likely pathogenic variant on chromosome 14q22.1 (NM_024884.2: c.178G > A; pGly60Arg) in the gene encoding for L-2-hydroxyglutarate dehydrogenase (L2HGDH) (OMIM #236792). Therefore, using the L2HGDH gene study is beneficial for L2HGA diagnosis.

Antimicrobial effect of garlic against foodborne pathogens in ground mutton.

The antimicrobial effect of fresh garlic (20, 30, and 50 g/kg) and the equivalent concentrations of garlic oil (80, 120, and 200 mg/kg) was investigated in ground mutton during storage at 4 °C. By day 6 and thereafter, mutton meatballs treated with 50 g/kg of fresh garlic and 200 mg/kg garlic oil exhibited a significant decline in psychrotrophic and Pseudomonas counts in comparison with control. Fresh garlic added at a concentration of 50 g/kg exhibited the highest antimicrobial effect, followed by garlic oil at 200 mg/kg, fresh garlic at 30 g/kg, and garlic oil at 120 mg/kg. By the 15th day of storage, the fresh garlic added at concentrations of 50 and 30 g/kg and garlic oil added at concentrations of 120, and 200 mg/kg inactivated the populations of foodborne pathogens artificially inoculated into ground mutton and exhibited significant (P < 0.01) lower counts in Salmonella Typhimurium, Escherichia coli O157:H7, Listeria monocytogenes, and Staphylococcus aureus by more than 3 logs CFU/g, in comparison to control. Therefore, fresh garlic and garlic oil can be used as natural antimicrobial food additives to extend the shelf life and inactivate the populations of foodborne pathogens in meat products.

Climate anxiety, environmental attitude, and job engagement among nursing university colleagues: a multicenter descriptive study.

BACKGROUND: Climate change, a pervasive global phenomenon, exerts discernible impacts on the physical, social, and psychological dimensions of well-being. The apprehension surrounding this complex environmental issue has reached a critical juncture, with over 76,000 individuals across more than thirty nations expressing profound levels of concern, characterizing their anxiety as either "very" or "extremely" pronounced. This surge in awareness regarding the potential consequences of climate change has given rise to an emergent and escalating challenge known as climate anxiety. This distinctive form of anxiety manifests through profound feelings of fear, helplessness, and despair elicited by the impending repercussions of climate change. Notably, the intersection of climate anxiety with occupational domains, particularly within the context of Nursing University Colleagues, suggests a nuanced relationship with job engagement, wherein the psychological responses to climate change may influence professional commitment and involvement. AIM OF THE STUDY: To examine the correlation among Climate Anxiety, Environmental Attitude, and Job Engagement among Nursing University Colleagues comprising eight distinct nursing faculties. DESIGN: A multicenter descriptive, cross-sectional research design study followed. SUBJECT: Three hundred fifty-nine participants from the Centre, Delta, West, Suez Canal, and Upper regions of Egypt using a stratified random cluster sampling technique. MEASUREMENTS: Social and health related to climate data structured questionnaire, climate anxiety scale, environmental attitude inventory, and job engagement scale. RESULTS: The influence of demographics on climate anxiety, environmental attitude, and job involvement was not observed. Nevertheless, geographical variations emerged as a noteworthy factor. A statistically significant inverse correlation was identified between climate anxiety, job engagement dimensions, and the overall score of environmental attitudes. CONCLUSION: Climate anxiety was strongly associated with environmental attitudes and job engagement among nursing university colleagues. Higher climate anxiety is associated with a lower attitude towards the environment and decreased job engagement. Additionally, a higher attitude towards the environment is associated with decreased overall engagement in participants' jobs. IMPLICATIONS: The study's patterns make it clear how important it is to provide targeted psycho-educational interventions to help reduce climate anxiety among the group of nursing university colleagues. The imperative lies not only in alleviating the immediate psychological distress associated with heightened climate anxiety but also in fostering adaptive coping mechanisms. By doing so, these interventions serve as instrumental tools in nurturing resilience, thereby fortifying the mental well-being of nursing professionals amidst the evolving landscape of climate-related concerns.

Does a program-based cognitive behavioral therapy affect insomnia and depression in menopausal women? A randomized controlled trial.

BACKGROUND: Menopausal women often complain of a range of physical and psychological symptoms known as menopausal syndrome. These symptoms are associated with fluctuating hormone levels, sleep disturbances, and mood swings. AIM: This study aimed to examine the efficacy of a program-based cognitive behavioral group therapy (CBT) for insomnia and depression among women experiencing menopause. METHODS: A randomized controlled trial of 88 women experiencing menopause was conducted in Egypt from June to September 2022 in outpatient clinics at Mansoura University Hospitals in Egypt. Participants were randomly assigned to a control group (45 women) and an intervention group (43 women). The intervention group received 7 weeks of CBT sessions. Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), and Beck Depression Inventory 2nd Edition (BDI-II) were administered before and after the intervention. RESULTS: In the intervention group, there was a significant difference in scores of the subdomains of PSQI, including sleep efficiency, daytime dysfunction, subjective sleep quality, and sleep disturbance (t = 8.911, 11.77, 7.638, and 11.054, respectively), while no significant difference in domains of using sleep medication, sleep duration, and sleep latency. Significant improvements were observed between pre-and-post-intervention in the intervention group for the total scores of PSQI, ISI, and BDII-II (t = 12.711, 16.272, and 12.384, respectively), indicating a large effect size for the three studied variables (r = .81, .87, .8, respectively). LINKING EVIDENCE TO ACTION: This study demonstrated the efficacy of group CBT for lowering insomnia and depression in women experiencing menopause. Thus, results indicated the need of considering prompt and appropriate interventions such as CBT as a safe treatment option to prevent the aggravation of sleep and emotional problems for menopausal women. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05920460.

Adequate bone healing after supplementary fixation of periprosthetic total knee arthroplasty fractures using Luque cerclage wiring: a retrospective case series.

PURPOSE: Cerclage wiring is a well-known supplemental fixation technique that can be used in many types of fractures. With the tendency toward minimally invasive approaches in the management of periprosthetic total knee arthroplasty (TKA) fractures, and with absence of a dedicated study that reports the results of cerclage wiring in TKA fractures in particular, the aim of this retrospective study is to report the outcomes of supplementary cerclage wiring using simple Luque wires in fractures of distal femur associated with TKA. METHOD: Eighteen cases, with a mean age of 77.2 years had complete follow-up data and had their radiographs and clinical data assessed for this study. Patients received cerclage wiring along with plates, retrograde nailing or around cracked femoral shaft overlying revision TKA femoral stem during the surgical management of periprosthetic TKA distal femur fractures. RESULTS: Fracture healing with adequate callus formation occurred in all 18 cases at a mean of 11.4 weeks postoperatively. None of the cases had any vascular injury, and after a mean clinical follow-up of 51 weeks, none of the cases had nonunion or hardware complications. One case had postoperative periprosthetic infection that developed 8 months after full fracture healing and had a two-stage revision using revision stemmed TKA and protective cerclage wiring with successful eradication of infection. CONCLUSION: Supplementary cerclage wiring in distal femur TKA fractures can aid in enhanced bone healing with minimal complications, provided that adequate reduction and rigid fixation were achieved. This study reflects the level of evidence IV.

Integrated proteomics reveals alterations in sarcomere composition and developmental processes during postnatal swine heart development.

The neonatal swine heart possesses an endogenous ability to regenerate injured myocardium through the proliferation of pre-existing cardiomyocyte (CM) populations. However, this regenerative capacity is lost shortly after birth. Normal postnatal developmental processes and the regenerative capacity of mammalian hearts are tightly linked, but not much is known about how the swine cardiac proteome changes throughout postnatal development. Herein, we integrated robust and quantitative targeted "top-down" and global "bottom-up" proteomic workflows to comprehensively define the dynamic landscape of the swine cardiac proteome throughout postnatal maturation. Using targeted top-down proteomics, we were able to identify significant alterations in sarcomere composition, providing new insight into the proteoform landscape of sarcomeres that can disassemble, a process necessary for productive CM proliferation. Furthermore, we quantified global changes in protein abundance using bottom-up proteomics, identified over 700 differentially expressed proteins throughout postnatal development, and mapped these proteins to changes in developmental and metabolic processes. We envision these results will help guide future investigations to comprehensively understand endogenous cardiac regeneration toward the development of novel therapeutic strategies for heart failure.

The role of hormones and neurons in cardiomyocyte maturation.

The heart undergoes profound morphological and functional changes as it continues to mature postnatally. However, this phase of cardiac development remains understudied. More recently, cardiac maturation research has attracted a lot of interest due to the need for more mature stem cell-derived cardiomyocytes for disease modeling, drug screening and heart regeneration. Additionally, neonatal heart injury models have been utilized to study heart regeneration, and factors regulating postnatal heart development have been associated with adult cardiac disease. Critical components of cardiac maturation are systemic and local biochemical cues. Specifically, cardiac innervation and the concentration of various metabolic hormones appear to increase perinatally and they have striking effects on cardiomyocytes. Here, we first report some of the key parameters of mature cardiomyocytes and then discuss the specific effects of neurons and hormonal cues on cardiomyocyte maturation. We focus primarily on the structural, electrophysiologic, metabolic, hypertrophic and hyperplastic effects of each factor. This review highlights the significance of underappreciated regulators of cardiac maturation and underscores the need for further research in this exciting field.

Middle East Respiratory Syndrome Coronavirus Infection Elicits Long-lasting Specific Antibody, T and B Cell Immune Responses in Recovered Individuals.

BACKGROUND: The Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic zoonotic betacoronavirus and a global public health concern. Better undersetting of the immune responses to MERS-CoV is needed to characterize the correlates of protection and durability of the immunity and to aid in developing preventative and therapeutic interventions. Although MERS-CoV-specific circulating antibodies could persist for several years post-recovery, their waning raises concerns about their durability and role in protection. Nonetheless, memory B and T cells could provide long-lasting protective immunity despite the serum antibodies levels. METHODS: Serological and flow cytometric analysis of MERS-CoV-specific immune responses were performed on samples collected from a cohort of recovered individuals who required intensive care unit (ICU) admission as well as hospital or home isolation several years after infection to characterize the longevity and quality of humoral and cellular immune responses. RESULTS: Our data showed that MERS-CoV infection could elicit robust long-lasting virus-specific binding and neutralizing antibodies as well as T- and B-cell responses up to 6.9 years postinfection regardless of disease severity or need for ICU admission. Apart from the persistent high antibody titers, this response was characterized by B-cell subsets with antibody-independent functions as demonstrated by their ability to produce tumor necrosis factor α (TNF-α), interleukin (IL)-6, and interferon γ (IFN-γ) cytokines in response to antigen stimulation. Furthermore, virus-specific activation of memory CD8+ and CD4+ T cell subsets from MERS-recovered patients resulted in secretion of high levels of TNF-α, IL-17, and IFN-γ. CONCLUSIONS: MERS-CoV infection could elicit robust long-lasting virus-specific humoral and cellular responses.

Antibody-Based Therapeutics for the Treatment of Renal Cell Carcinoma: Challenges and Opportunities.

Renal cell carcinoma (RCC) is among the top 10 most common cancers in both men and women with an estimated 75 000 cases each year in the US. Over the last decade, the therapeutic landscape for patients with metastatic RCC has significantly evolved, with immunotherapy emerging as the new front-line therapy. Despite significant improvement in toxicity profile and survival outcomes, key concerns such as patient selection, treatment sequencing, and intrinsic and acquired resistance remain unresolved. Emerging options such as antibody-based therapeutics (eg, anti-CD70, anti-CA9, and anti-ENPP3) are being explored in clinical trials for patients with cancer resistant or refractory to current immunotherapies. Despite positive results for hematological cancers, breast cancer, and more recently bladder cancer, most antibody-based therapies failed to improve the outcomes in patients with advanced RCC. This underscores the need to understand the underlying causes of failed responses to this treatment class, which will ultimately support the rational design of more effective and tolerable treatments. In this review, we summarize the evolving landscape of RCC therapeutics and describe recent clinical trials with emerging antibody-based therapeutics. We also describe the challenges that need to be overcome for the successful creation of therapeutic antibodies for treating RCC.

Antifungal activity of Lysinibacillus macroides against toxigenic Aspergillus flavus and Fusarium proliferatum and analysis of its mycotoxin minimization potential.

BACKGROUND: Toxigenic fungi (Aspergillus and Fusarium) and their metabolites represent the major cause of corn and corn-based products contamination and consequently lead to severe economic and health issues. AIM: Our current study aimed to investigate the efficacy of using L. macroides Bac6 as a biological control agent against the toxigenic fungi; A. flavus f10 and F. proliferatum f30 and their mycotoxins. RESULTS: The results illustrated that A. flavus f10 produced the aflatoxins AFB1 and AFG2 with concentrations of 21.239 and 13.593 ppb, respectively. While F. proliferatum f30 produced fumonisin B1 (9600 ppb). Furthermore, L. macroides showed a high potential for inhibition of toxigenic fungal growth using a dual culture method. F. proliferatum f30 and A. flavus f10 were found to be inhibited by a percentage of 80 and 62.5%, respectively. The results were confirmed using the scanning electron microscope. The antagonistic bacteria, L. macroides, showed chitinase productivity and activity of 26.45 U/L and 0.12 U/mL/min, respectively, which illustrates its potential application as a biocontrol agent. The GC-MS analysis revealed an abundance of Pyrrolo[1,2-a] pyrazine-1,4-dione, Hexahydro in the bacterial supernatant that exhibited antifungal characteristics. L. macroides had a significant reduction of AFB1 and AFG2 produced by A. flavus f10, recording 99.25% and 99% inhibition, respectively. It also showed strong inhibition of fumonisin B1 (90% inhibition) produced by F. proliferatum f30. CONCLUSION: Thus, the current study is a prospective study evaluating for the first time the potential impact of L. macroides Bac6 against the toxigenic fungi and their toxins.

One-way light flow by spatio-temporal modulation.

The unidirectional flow of electrons that takes place in a conventional electronic diode has been a cornerstone in the development of the field of electronics. Achieving an equivalent one-way flow for light has been a long-standing problem. While a number of concepts have been suggested recently, attaining a unidirectional flow of light in a two-port system (e.g., a waveguiding configuration) is still challenging. Here, we present what we believe to be a novel approach for breaking reciprocity and achieving one-way flow of light. Taking a nanoplasmonic waveguide as an example, we show that a combination of time-dependent interband optical transitions, when in systems exhibiting a backward wave flow, can yield light transmission strictly in one direction. In our configuration, the energy flow is unidirectional: light is fully reflected in one direction of propagation, and is unperturbed in the other. The concept can find use in a range of applications including communications, smart windows, thermal radiation management, and solar energy harvesting.

What are the current anti-COVID-19 drugs? From traditional to smart molecular mechanisms.

BACKGROUND: Coronavirus disease 19 (COVID-19) is the disease caused by SARS-CoV-2, a highly infectious member of the coronavirus family, which emerged in December 2019 in "Wuhan, China". It induces respiratory illness ranging from mild symptoms to severe disease. It was declared a "pandemic" by the World Health Organization (WHO) in March 2020. Since then, a vast number of clinical and experimental studies have been conducted to identify effective approaches for its prevention and treatment. MAIN BODY: The pathophysiology of COVID-19 represents an unprecedented challenge; it triggers a strong immune response, which may be exacerbated by "a cytokine storm syndrome". It also induces thrombogenesis and may trigger multi-organ injury. Therefore, different drug classes have been proposed for its treatment and prevention, such as antivirals, anti-SARS-CoV-2 antibody agents (monoclonal antibodies, convalescent plasma, and immunoglobulins), anti-inflammatory drugs, immunomodulators, and anticoagulant drugs. To the best of our knowledge, this review is the first to present, discuss, and summarize the current knowledge about the different drug classes used for the treatment of COVID-19, with special emphasis on their targets, mechanisms of action, and important adverse effects and drug interactions. Additionally, we spotlight the latest "October 2023" important guidelines (NIH, IDSA, and NICE) and FDA approval or authorization regarding the use of these agents in the management of COVID-19. CONCLUSION: Despite the wide array of therapeutic strategies introduced for the treatment of COVID-19, one of the most prominent therapeutic challenges is SARS-CoV-2 mutations and emerging new variants and subvariants. Currently, the anti-COVID-19 drug pipeline is continuously affording novel treatments to face this growing challenge.

The risk of central nodal metastasis based on prognostic factors of the differentiated thyroid carcinoma: a systematic review and meta-analysis study.

BACKGROUND AND AIM: Despite improving the 10-year disease-free-survival, prophylactic central neck dissection (pCND) in differentiated thyroid carcinoma (DTC) should only be considered in patients with high risk factors for lymph node (LN) metastasis due to the increases in the risk of postoperative complications. Our aim was to identify the risk factors for central lymph node metastasis (CLNM) in DTC. METHOD: We searched PubMed, Scopus, Web of science, Cochrane library for eligible studies from inception to November 1, 2021 and a systematic review and meta-analysis were carried out to identify the risk factors for CLNM in DTC. RESULTS: We included 41 studies with total of 27,741 patients in this study. The pooled results in this meta-analysis showed that these risk factors were significantly associated with CLNM: age < 45 years (odds ratio (OR) 1.64, 95% confidence interval (CI) 1.34-1.99, p < 0.00001), male sex (OR 1.73, 95% CI 1.54-1.93, p < 0.00001), multifocality (OR 1.87, 95% CI 1.59-2.19, p < 0.00001), bilateral disease (OR 1.43, 95% CI 1.15-1.78, p < 0.001), capsular invasion (OR 1.67, 95% CI 1.10-2.54, p < 0.02), lymphovascular invasion (OR 4.89, 95% CI 2.76-8.66, p < 0.00001) and extra-thyroidal extension (OR 2.43, 95% CI 1.97-3.00, p < 0.00001). In addition, young age (< 45 years), male sex, multifocality, and extra-thyroidal extension were significantly associated with large-volume CLNM in clinically N0 DTC patients. However, the presence of Hashimoto's thyroiditis was not a predictors of large-volume CLNM. CONCLUSION: Young age (< 45 years), male sex, bilateral disease, multifocality, capsular invasion, lymphovascular invasion and extra-thyroidal extension are significantly associated with CLNM and pCND would be expected to have a higher yield in patients with these risk factors.

An Electrochemical Sensor for Sulfadiazine Determination Based on a Copper Nanoparticles/Molecularly Imprinted Overoxidized Polypyrrole Composite.

To protect consumers from risks related to overexposure to sulfadiazine, total residues of this antibacterial agent in animal-origin foodstuffs not exceed international regulations. To this end, a new electrochemical sensor based on a molecularly imprinted polymer nanocomposite using overoxidized polypyrrole and copper nanoparticles for the detection of sulfadiazine is elaborated. After optimization of the preparation of the electrochemical sensors, their differential pulse voltammetric signal exhibits an excellent stability and reproducibility at 1.05 V, with a large linear range between 10-9 and 10-5 mol L-1 and a low detection limit of 3.1 × 10-10 mol L-1. The produced sulfadiazine sensor was successfully tested in real milk samples. The combination of the properties of the electrical conduction of copper nanoparticles with the properties of the preconcentration of the molecularly imprinted overoxidized polypyrrole allows for the highly sensitive detection of sulfadiazine, even in real milk samples. This strategy is new and leads to the lowest detection limit yet achieved, compared to those of the previously published sulfadiazine electrochemical sensors.