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Cellular rejuvenation therapies represent a transformative frontier in addressing age-related decline and extending human health span. By targeting fundamental hallmarks of aging-such as genomic instability, epigenetic alterations, mitochondrial dysfunction, and cellular senescence-these therapies aim to restore youthful functionality to cells and tissues, offering new hope for treating degenerative diseases. Recent advancements have showcased a range of strategies, including epigenetic reprogramming, senolytic interventions, mitochondrial restoration, stem cell-based approaches, and gene-editing technologies like CRISPR. Each modality has demonstrated substantial potential in preclinical models and is now being cautiously explored in early-stage clinical trials. However, translating these therapies from the laboratory to clinical practice presents unique challenges: safety concerns, delivery precision, complex regulatory requirements, ethical considerations, and high costs impede widespread adoption. This review examines the current landscape of cellular rejuvenation, highlighting key advancements, potential risks, and the strategies needed to overcome these hurdles.

Tetrahydrocarbazole is the central core for several biologically active alkaloids, and regioselective synthesis of this core is a challenging task. Herein, we report an efficient strategy for the synthesis of this core involving palladium-catalyzed intramolecular arylation reaction with excellent regioselectivity (>99%) starting from N -phenyl-bromoalkene without having any relocation of double bonds via competitive palladium-catalyzed isomerization reaction. Broad functional group tolerance and exclusive regioselectivity have been observed for meta-substituted halide substrates. Furthermore, this reaction can be scalable on the gram scale.

Recent literature indicates that post-COVID-19 patients suffer from a plethora of complications, including chemosensory dysfunction. However, little attention has been given to understand the interactions between chemosensory, trigeminal, and salivary dysfunctions in these patients. The aims of this study were (1) to investigate the prevalence and combinations of chemosensory, trigeminal, and salivary dysfunctions, (2) to identify the odorants/tastants that are compromised, and (3) to explore possible associations between the four dysfunctions in post-COVID-19 patients. One hundred post-COVID-19 patients and 76 healthy controls (pre-COVID-19) were included in this cross-sectional, case-controlled study. Participants' smell, taste, trigeminal, and salivary functions were assessed. The patients had a significantly higher prevalence of parosmia (80.0%), hyposmia (42.0%), anosmia (53.0%), dysgeusia (34.0%), complete ageusia (3.0%), specific ageusia (27.0%), dysesthesia (11.0%) and dry mouth (18.0%) compared to controls (0.0% for all parameters, except 27.6% for hyposmia). Complete loss of bitter taste was the most prevalent specific ageusia (66.7%) and coffee was the most common distorted smell (56.4%). Seven different combinations of dysfunction were observed in the patients, the most common being a combination of olfactory and gustatory dysfunction (48.0%). These findings indicate that post-COVID-19 patients experience a range of chemosensory, trigeminal, and salivary disturbances, occurring in various combinations., (© 2024. The Author(s).)

Pericentric heterochromatin (PCH) plays an essential role in the maintenance of genome integrity and alterations in PCH have been linked to cancer and aging. HP1 α, β, and γ, are hallmarks of constitutive heterochromatin that are thought to promote PCH structure through binding to heterochromatin-specific histone modifications and interaction with a wide range of factors. Among the less understood components of PCH is the histone H2A variant H2A.Z, whose role in the organization and maintenance of PCH is poorly defined. Here we show that there is a complex interplay between H2A.Z and HP1 isoforms in PCH. While the loss of HP1α results in the accumulation of H2A.Z.1 in PCH, which is associated with a significant decrease in its mobile fraction, H2A.Z.1 binds preferentially to HP1β in these regions. Of note, H2A.Z.1 downregulation results in increased heterochromatinization and instability of PCH, reflected by accumulation of the major epigenetic hallmarks of heterochromatin in these regions and increased frequency of chromosome aberrations related to centromeric/pericentromeric defects. Our studies support a role for H2A.Z in genome stability and unveil a key role of H2A.Z in the regulation of heterochromatin-specific epigenetic modifications through a complex interplay with the HP1 isoforms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 González, Bosch-Presegué, Marazuela-Duque, Guitart-Solanes, Espinosa-Alcantud, Fernandez, Brown, Ausió, Vazquez, Singh, Fraga and Vaquero.)

Using a new method for bulk preparation of early stage embryos, we have investigated the role played by putative Planococcus citri H3K9 and H4K20 histone methyl transferases (HMTases) in regulating heterochromatinization of the imprinted paternal chromosomal set in male embryos. We found that H3K9 and H420 HMTases are required for heterochromatinization of the paternal chromosomes. We present evidence that both HMTases maintain the paternal "imprint" during the cleavage divisions when both parental chromosome sets are euchromatic. A testable model that accommodates our findings is proposed., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Himalayan musk deer (Moschus leucogaster) is classified as an endangered species by IUCN with a historically misunderstood distribution due to misidentification with other species of musk deer, Moschus spp. Taking advantage of recent genetic analyses confirming the species of various populations in Nepal and China, we produced an accurate estimate of the species' current and future distribution under multiple climate change scenarios. We collected high-quality occurrence data using systematic surveys of various protected areas of Nepal to train species distribution models. The most influential determinants of the distribution of Himalayan musk deer were precipitation of the driest quarter, temperature seasonality, and annual mean temperature. These variables, and precipitation in particular, determine the vegetation type and structure in the Himalaya, which is strongly correlated with the distribution of Himalayan musk deer. We predicted suitable habitats between the Annapurna and Kanchenjunga region of Nepal Himalaya as well as the adjacent Himalaya in China. Under multiple climate change scenarios, the vast majority (85-89%) of current suitable sites are likely to remain suitable and many new areas of suitable habitat may emerge to the west and north of the current species range in Nepal and China. Two-thirds of current and one-third of future suitable habitats are protected by the extensive network of protected areas in Nepal. The projected large gains in suitable sites may lead to population expansion and conservation gains, only when the threat of overexploitation and population decline is under control., (© 2023. Springer Nature Limited.)

In this study, we propose an ensemble model for the detection of diabetic retinopathy (DR) illness that is driven by transfer learning. Due to diabetes, the DR is a problem that affects the eyes. The retinal blood vessels in a person with high blood sugar deteriorate. The blood arteries may enlarge and leak as a result, or they may close and stop the flow of blood. If DR is not treated, it can become severe, damage vision, and eventually result in blindness. Medical experts study the colored fundus photos for this reason in order to manually diagnose disease, however this is a perilous technique. As a result, the condition was automatically identified utilizing retinal scans and a number of computer vision-based methods. A model is trained on one task or datasets employing the transfer learning (TL) technique, and then the pre-trained models or weights are applied to another task or dataset. Six deep learning (DL)-based convolutional neural network (CNN) models were trained in this study using huge datasets of reasonable photos, including DenseNet-169, VGG-19, ResNet101-V2, Mobilenet-V2, and Inception-V3. We also applied a data-preprocessing strategy to improve the accuracy and lower the training costs in order to improve the results. The experimental results demonstrate that the suggested model works better than existing approaches on the same dataset, with an accuracy of up to 98%, and detects the stage of DR., (© 2023. International Federation for Medical and Biological Engineering.)

Unilateral proptosis is an abnormality in which one eye sticks out forward more than the other. Bulging of the eye is commonly seen in Graves' ophthalmopathy, but it's mostly bilateral. Thyroid eye disease presents as the most common extrathyroidal manifestation of Graves' disease, and rarely leads to unilateral proptosis. A 25-year-old female with a history of weight loss, menstrual irregularities, and palpitations presented with progressive right eye bulging, which was further confirmed by magnetic resonance imaging and biochemical investigations. Magnetic resonance imaging of the orbit revealed unilateral extraocular muscle enlargement and enhancement with sparing of the tendons. Timely therapy is crucial for reversing the ocular manifestations of thyroid eye disease., Competing Interests: The author(s) declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Agenesis of the dorsal pancreas (ADP) is a clinically rare entity that occasionally presents with abdominal pain. It is also association with various disorders of glucose metabolism., Case Presentation: A 23-year-old male presented with continuous epigastric pain for 4 h and intermittent vomiting. He has a history of experiencing recurrent abdominal pain and diarrhoea for the past 5 years. Additionally, he has been diagnosed with type 1 diabetes mellitus for 15 years. Contrast-enhanced computed tomography of the abdomen showed the absence of body and tail of the pancreas., Discussion: ADP is caused by unknown factors, but may be linked to genetic mutations or changes in signalling pathways related to retinoic acid and hedgehog. Symptoms can be absent, but may include abdominal pain, pancreatitis, and hyperglycaemia due to beta-cell dysfunction and insulin deficiency. Imaging modalities, such as contrast tomography or magnetic resonance cholangiopancreatography, or endoscopic retrograde cholangiopancreatography, are crucial in the diagnosis of ADP., Conclusion: It is important to consider ADP as a differential diagnosis in patients with glucose metabolism disorders and associated symptoms such as abdominal pain, pancreatitis, or steatorrhea. It requires the combined use of imaging modalities such as ultrasound, contrast tomography, magnetic resonance cholangiopancreatography, or endoscopic retrograde cholangiopancreatography, as ultrasound alone may not provide a complete diagnosis., Competing Interests: None., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Patients suffering from psychiatric disorders face many difficulties due to their condition, medications and lifestyle. Oral health and nutrition may be affected, further complicating their lives. Our aim was to provide in-depth information on oral health and nutritional factors in a small group of patients in short-term psychiatric ward., Methods: Twenty-three patients (mean age 36, average medications five) were recruited during short-term hospitalization in a psychiatric ward. Inclusion criteria: anxiety, psychosis and/or depression, and use of at least one antidepressant or anxiolytic/antipsychotic drug with xerostomia as a known side effect. Subjective oral dryness was evaluated using the Shortened Xerostomia Inventory (SXI). Oral examination included Clinical Oral Dryness Score (CODS), secretion of unstimulated (UWS) and stimulated whole saliva (SWS), and evaluation of dental, gingival, and periodontal status. Self-reported complaints of oral disorders were recorded. The Oral Health Impact Profile-14 (OHIP-14) was used to explore oral health-related quality of life. Nutritional status was assessed using the Patient-Generated Subjective Global Assessment Short Form (PG-SGA-SF), and diet quality was assessed using the Mediterranean diet score (KIDMED)., Results: Compared to healthy controls, the patients had significantly higher SXI scores and CODS, and SWS secretion was lower. Complaints of dysgeusia and halitosis were significantly more frequent among patients. Gingivitis was more common in patients. OHIP-14 scores were much higher in the patients, and they reported significantly poorer oral and general health. Most patients lacked a regular meal pattern. Very low diet quality was observed in five patients, while improvements were needed in twelve. " Dry mouth " and " No appetite, just did not feel like eating " were the most common symptoms preventing patients from eating enough. The PG-SGA-SF symptoms component score showed a strong negative correlation with self-reported oral health, and a strong positive correlation with OHIP-14., Conclusion: This relatively small group of patients in short-term psychiatric ward had both reduced oral health and poor oral health-related quality of life. Furthermore, their nutritional intake was affected by their oral health problems. Although larger groups need to be studied, these findings indicate that oral health and nutrition should be evaluated and adjusted in these patients to improve their overall care., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Frigaard, Hynne, Randsborg, Mellin-Olsen, Young, Rykke, Singh, Hove, Hofgaard and Jensen.)

'Age reprogramming' refers to the process by which the molecular and cellular pathways of a cell that are subject to age-related decline are rejuvenated without passage through an embryonic stage. This process differs from the rejuvenation observed in differentiated derivatives of induced pluripotent stem cells, which involves passage through an embryonic stage and loss of cellular identity. Accordingly, the study of age reprogramming can provide an understanding of how ageing can be reversed while retaining cellular identity and the specialised function(s) of a cell, which will be of benefit to regenerative medicine. Here, we highlight recent work that has provided a more nuanced understanding of age reprogramming and point to some open questions in the field that might be explored in the future., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

Meckel's diverticulum (MD) is the most common congenital anomaly of the gastrointestinal tract. Most cases are asymptomatic and when symptomatic, preoperative diagnosis of MD is poor. Intestinal obstruction, Malena or hematochezia, and inflammation are major symptoms. We report three cases of 18-month, 2-year, and 9-year old male patients presenting with intestinal obstruction., Competing Interests: There is no conflict of interest to declare., (© 2022 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

Introduction: Hypothyroidism is a common condition in the general population that presents a wide array of medical, neurological and psychiatric symptoms. However, hypothyroidism rarely leads to acute psychosis, termed myxedema psychosis (MP) and is often missed by many physicians., Case Presentation: Here we report a case of a 36-years-old female who presented with a one-week history of abnormal behavior, delusions and hallucinations. Investigations revealed a high thyroid-stimulating-hormone (TSH)of 78.60 mlU/mL and low free thyroxine (FT4) of 0.64 pmol/L. Diagnosed with hypothyroidism, she was treated with oral thyroid hormone replacement (l-thyroxine 75 μg/day) with antipsychotics and her symptoms settled within days. She was discharged off antipsychotics and advised to adhere to thyroxine replacement and to follow up for Thyroid function test (TFT)., Discussion: Myxedema psychosis is an uncommon manifestation of the common endocrine disease hypothyroidism. The atypical nature of presentations occasionally complicates diagnostics. When approaching a 'first-episode psychosis,' it is essential to perform a complete organic screen consistently., Conclusion: Acute myxedema madness should be considered in the differential diagnosis of acute psychosis in patients with hypothyroidism., Competing Interests: Authors have no conflict of interest to declare., (© 2022 The Authors.)

Introduction: Diclofenac is considered a generally safe medication, and cause few side effects like dyspepsia, diarrhea/constipation, nausea, and vomiting, stomach bleeding, rash, urticaria, photosensitivity reactions, acute renal failure, analgesic nephropathy, bone marrow and liver diseases. Rarely, it causes anaphylactic reaction., Case Presentation: We report a case of 40 years male who developed anaphylactic reaction after intravenous infusion with diclofenac., Discussion: Both the pulmonary embolism and anaphylaxis guidelines emphasize the importance of a thorough evaluation when making a diagnosis. Mast cells secrete tryptase, a neutral protease that is specifically concentrated in the secretory granules of human mast cells (but not basophils), along with histamine, as a marker of mast cell activation., Conclusion: Although intravenous diclofenac sodium is a safe and often used medicine, it can cause severe and perhaps fatal anaphylactic responses., Competing Interests: Authors have no conflict of interest to declare., (© 2022 The Author(s).)

Introduction: Atypical spindle cell lipomatous tumor (ASPLT), a separate entity for the group of benign/low grade adipocytic neoplasm that is characterized by adipocyte adequacy and the presence of lipoblast-like cells and spindle cells at varying degrees., Case Presentation: Here, we report a rare case of 60 years old male with atypical spindle cell lipomatous tumor in the anterior abdominal wall., Discussion: Histopathology is the gold standard for establishing the diagnosis and grade of soft tissue tumor and consistent radiology-pathology correlation is essential to avoid any diagnostic pitfalls [1]. Ultrasound is preferred as an initial investigation for superficially located lesions., Conclusion: ASPLT show a wide variety of microscopic features, and differential diagnosis is important and difficult. Recognition of morphologic clues and immunohistochemistry/molecular tests to confirm the diagnosis., Competing Interests: None., (© 2022 The Authors.)

Introduction: Parotid fistula is an uncommon consequence of surgical or non-surgical trauma to the parotid gland or the area surrounding it. To treat it, a variety of pharmacological medicines and surgical techniques are used, each with their own set of benefits, drawbacks, and patient preferences., Case Presentation: We present the successful care of a young female with post-traumatic parotid fistula using hypertonic saline injections into the parotid substance, which is a simple yet efficient approach of treating this abnormality., Discussion: Thermodynamic and physicochemical calculations suggest that hypertonic saline solutions work to close parotid fistula by causing conformational denaturation of the cell membrane proteins in situ and saline can be diluted to a point where there will be no cellular toxicity. It is advised that temperature of the saline should be raised above body temperature to enhance the fibrosing property of physiologic saline., Conclusion: The use of hypertonic hot saline injections combined with compression dressing is a cost-effective, patient-friendly, and almost complication-free approach of treating parotid fistulas with promising results., Competing Interests: Authors have no conflict of interest to declare., (© 2022 The Authors.)

Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Purpose: To investigate taste and smell function in survivors, with a minimum of 2 years since treatment of childhood medulloblastoma (MB)/central nervous system supratentorial primitive neuroectodermal tumor (CNS-PNET)., Methods: This cross-sectional study included 40 survivors treated ≤ 20 years of age. Taste strips with four concentrations of sweet, sour, salt, and bitter were used to assess taste function in all participants. Score from 0 to 16; ≥ 9 normogeusia, < 9 hypogeusia, and complete ageusia which equals no sensation. No sensation of a specific taste quality equals ageusia of that quality. Thirty-two participants conducted smell testing using three subtests of Sniffin' sticks: threshold, discrimination, and identification. Together they yield a TDI-score from 1 to 48; functional anosmia ≤ 16.00, hyposmia > 16.00- < 30.75, normosmia ≥ 30.75- < 41.50, and ≥ 41.50 hyperosmia. Results were compared with normative data. Survivors rated their taste and smell function using a numerical rating scale (NRS) score 0-10., Results: Forty survivors with a mean time since treatment of 20.5 years, 13 (32.5%) were diagnosed with hypogeusia, nine (22.5%) of these being ageusic to one or more taste qualities. Seventeen (53%) of 32 participants were diagnosed with hyposmia. The mean scores of the olfactory subtests, and TDI score were significantly lower than normative data (P < 0.0001). The mean NRS scores of smell and taste function were 7.9 ± 1.5 and 8 ± 1.3, respectively., Conclusion: Our study showed impaired taste and smell function in survivors of childhood MB/CNS-PNET using objective measurements. However, subjective ratings did not reflect objective findings., (© 2022. The Author(s).)

Native germplasm resources are adapted to specific ecological niches. They have sustained over generations owing to the preference of local communities for their unique taste, the utility to particular dishes, and the low cost of cultivation. They may help eradicate malnutrition and act as a source for trait-linked genes. The present dataset comprises thirty-three native germplasm of maize collected from Rajasthan, Himachal Pradesh, and Andhra Pradesh states of India with an altitudinal variation of 386-2,028 m. They were evaluated for proximate composition, minerals, nutritional attributes, and antioxidant activity and compared with the standard values reported in the Indian Food Composition Table 2017 (IFCT2017). The nutritional profile showed moisture content in the range of 7.16-10.9%, ash 0.73-1.93%, crude protein 8.68-12.0%, crude fat 3.72-8.03%, dietary fiber 5.21-11.2%, and available carbohydrates 60.6-69.8%. Three accessions, namely, Malan 11 (7.06%), Malan 24 (7.20%), and Yellow Chamba Local 02 (8.03%) exhibited almost double the crude fat content as compared with the values notified in IFCT2017 (3.77). Total sugar content obtained was in the range of 5.00-11.3%, whereas the starch content was found between 50.9 and 64.9%. All the germplasm except Yellow Chamba Local reflected a higher protein content than reported values in IFCT2017 (8.80). Sathi, Safed Chamba Local, and Ragal Makka had nearly 12% protein content. Mineral malnutrition, mainly due to iron (Fe) deficiency, is a worldwide issue to science, humanity, and society. The mineral profile revealed that most germplasm had a higher iron content. Accessions with the iron content of nearly three times of IFCT2017 reported value were identified in germplasm belonging to three states. A negative relationship was observed between the altitude of the sample collection site and available carbohydrate content. In contrast, available carbohydrate showed inverse correlations with dietary fiber, protein, and fat content. The information generated in this study can be utilized to promote these germplasm as nutrifood, nutritional surveillance, labeling, and crop improvement programs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Langyan, Bhardwaj, Kumari, Jacob, Bisht, Pandravada, Singh, Singh, Dar, Kumar and Rana.)

Elusive species often use latrines which also serves as communication and information hubs. Thus, studying behavior at latrines may provide critical insights into the species' ecology and behavior. While it is established that musk deer use latrines for defecating, very little is known about the endangered Himalayan musk deer ( Moschus leucogaster ) and their latrines. We examined musk deer behavior from the various video clips lasting 238 min altogether, captured at latrine sites during both breeding and non-breeding seasons in the Annapurna Conservation Area of Nepal. A total of 428 visits by musk deer and 479 behavioral events by them were captured. We constructed an ethogram to describe musk deer behavior and compared behavior across individuals and sex using parametric and non-parametric tests. We found that musk deer are crepuscular and nocturnal animals. Both male and female musk deer repeatedly and independently visited shared latrine sites as well as exclusively used latrine sites. The proportion of male musk deer visited latrine sites were significantly higher than that of female musk deer. Hence, male musk deer were found more active (>2 times) than females during both seasons. The most frequently observed behavioral activities at the latrine sites were defecating, sniffing and browsing, followed by scrapping and covering, and ignoring the latrine sites. The defecating and sniffing activity were performed throughout breeding and non-breeding seasons to establish communication among peers and to claim territory. Based on the behaviors observed at the latrine sites, we can presume that Himalayan musk deer likely use latrines to convey various messages, including personality, maturity, sexual status, and territory marking among conspecifics. These findings of this study can be used for the conservation of musk deer in its natural habitat and replicated in captivity to enhance breeding performance that improves long-term conservation prospects for this species., Competing Interests: None declared., (© 2022 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Aims: The primary aim was to determine if the Nottingham Hip Fracture Score (NHFS) could be used to stratify 1-year mortality risk amongst periprosthetic hip fracture patients. The secondary aim was to identify 1year mortality rates amongst surgically managed periprosthetic hip fractures., Methods: Our electronic fracture database was interrogated for all Vancouver B or C periprosthetic fractures between September 2009 to April 2019; 83 patients were identified. All available data was then collected from radiographic, electronic and paper notes. The NHFS was retrospectively calculated for each patient. Statistical analysis was performed to identify factors significantly affecting 12month mortality using Akaike's information criterion corrected for small sample sizes (AICc), binomial logistic regression was performed using each variable; the p-values presented are for the coefficients of the regressor., Results: Periprosthetic fractures have a 1year mortality risk of 26.5%, 30 day mortality was 4.82%. The NHFS was found to be highly predictive of 1-year mortality amongst this patient cohort (p = 0.0001). We find that each unit increase in the NHFS is correlated with a 2.7times increase in mortality rate. There was no evidence that time lag from presentation to surgery led to an increased mortality (p = 0.455)., Conclusion: The NHFS can be used to stratify the 1-year mortality risk amongst patients who have periprosthetic hip fracture; this is a new finding not previously published to our knowledge. Given that time to surgery does not correlate with mortality, patients should be risk stratified on admission with NHFS. Time is then available to conduct a multi-disciplinary approach to optimize the patient, personnel and equipment. The introduction of a parallel multidisciplinary pathway to neck of femur fractures is long overdue and must be expedited., (Copyright © 2021 Elsevier Ltd. All rights reserved.)