The current and emerging Klotho-enhancement strategies.

Klotho is well known as a gene with antiaging properties. It has membrane and soluble forms, providing a unique system that controls various metabolic processes essential to health and disease. Klotho deficiency has been revealed to be associated with various aging-related disorders. Based on its various known and unknown protective properties, upregulating the Klotho gene may be a possible therapeutic and/or preventive approach in aging-related complications. Some agents, such as hormonal compounds, renin-angiotensin system inhibitors, antioxidants, peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists, statins, vitamin D receptor agonists, antioxidants, anti-inflammatory agents, mammalian target of rapamycin (mTOR) signaling inhibitors, and receptor-interacting serine/threonine-protein kinase 1 (RIPK1) inhibitors, can possibly lead to the upregulation and elevation of Klotho levels. Demethylation and deacetylation of the Klotho gene can also be considered other possible Klotho-enhancement methods. Some emerging techniques, such as RNA modifications, gene therapy, gene editing, and exosome therapy, probably have the potential to be applied for increasing Klotho. In the present study, these current and emerging Klotho-enhancement strategies and their underlying mechanisms were comprehensively reviewed, which could highlight some potential avenues for future research.

The Effects of Remdesivir and Dexamethasone on Renal Sirtuin-1 Expression and Renal Function in Male Rats.

Remdesivir (REM) and dexamethasone (DEX) both have been used to treat coronavirus disease 2019 (COVID-19). The present study aimed to evaluate the effects of REM and DEX on kidney structure and function with particular focus on the probable renal sirtuin-1 (SIRT1) expression alteration in rats. Twenty-four male Wistar rats were divided into four groups, as follows: group A (control) received normal saline (5 mL/kg/day for 10 days); group B (REM) received REM (17 mg/kg/day on the first day, and 8.5 mg/kg/day on the 2nd-10th days); group C (REM + DEX) received both REM (17 mg/kg/day on the first day, and 8.5 mg/kg/day on the 2nd-10th days) and DEX (7 mg/kg/day, for 10 days); group D (DEX) received DEX (7 mg/kg/day for 10 days). Renal SIRT1 expression and kidney structure and function-related factors were evaluated by standard methods. The mean levels of urea in the REM + DEX group (60.83 ± 6.77, mg/dL) were significantly higher than in the control (48.33 ± 3.01, mg/dL; p = 0.002) and DEX (51.22 ± 4.99, mg/dL; p = 0.018) groups. The mean levels of creatinine in the REM (0.48 ± 0.08, mg/dL) and REM + DEX (0.50 ± 0.04, mg/dL) groups were higher than in the control group (48.33 ± 3.0 mg/dL) significantly (p = 0.022 and p = 0.010, respectively). The renal SIRT1 expression was significantly (p = 0.018) lower in the REM + DEX group (0.36 ± 0.35) than in the control group (1.34 ± 0.48). Tubulointerstitial damage (TID) scores in REM + DEX-treated rats (2.60 ± 0.24) were significantly higher than in the control (0.17 ± 0.17, p = 0.001) and DEX (0.50 ± 0.29, p = 0.005) groups. The administration of DEX and REM might lead to kidney injury associated with SIRT1 downregulation.

The neutrophil-to-lymphocyte ratio as a new prognostic factor in cancers: a narrative review.

The increasing incidence of cancer globally has highlighted the significance of early diagnosis and improvement of treatment strategies. In the 19th century, a connection was made between inflammation and cancer, with inflammation recognized as a malignancy hallmark. The neutrophil-to-lymphocyte ratio (NLR), calculated from a complete blood count, is a simple and accessible biomarker of inflammation status. NLR has also been proven to be a prognostic factor for various medical conditions, including mortality classification in cardiac patients, infectious diseases, postoperative complications, and inflammatory states. In this narrative review, we aim to assess the prognostic potential of NLR in cancer. We will review recent studies that have evaluated the association between NLR and various malignancies. The results of this review will help to further understand the role of NLR in cancer prognosis and inform future research directions. With the increasing incidence of cancer, it is important to identify reliable and accessible prognostic markers to improve patient outcomes. The study of NLR in cancer may provide valuable insights into the development and progression of cancer and inform clinical decision-making.

The Effects of Vitamin B-Complex Supplementation on Serum Homocysteine Levels and Migraine Severity in Children A Randomized Controlled Trial.

Objectives: Given that deficiency in B vitamins can lead to the accumulation of homocysteine (Hcy), and hyperhomocysteinemia may have a role in migraine pathogenesis, the present prospective randomized double-blinded placebo-controlled trial aimed to evaluate the effect of vitamin B-complex supplementation on the alleviation of migraine in children through a possible reduction in Hcy levels. Materials & Methods: Ninety children under 15 years of age suffering from typical migraine were included in the present trial. They were randomly assigned into two groups (forty-five patients in each group) to receive either vitamin B-complex or a matching placebo for six months. Serum Hcy levels and headache characteristics were evaluated and compared before and after administering vitamin B-complex or placebo. Results: Unlike the placebo group, the monthly headache frequency, severity of headache, headache disability, and serum Hcy levels were significantly decreased after the vitamin administration. The headache duration was not significantly different before and after the treatment. In the vitamin group, there were significant positive correlations between the frequency and severity, frequency and disability, and severity and disability of headaches. Hcy also had significant positive correlations with the frequency and disability of headaches. In the placebo group, the only found significant correlation was between headache frequency and disability. Conclusion: The administration of vitamin B-complex might effectively relieve migraine severity in children by reducing serum Hcy. However, further studies are needed to confirm the results.

The possible anti-seizure properties of Klotho.

Recurrent seizures in epilepsy may lead to progressive neuronal damage, which can diminish health-related quality of life. Evaluation and control of pathological processes in the brain is valuable. It seems imperative that new markers and approaches for seizure alleviation be discovered. Klotho (Kl), an antiaging protein, has protective effects in the brain against neurological disorders. It may also have antiseizure effects by improving creatine transfer to the brain, upregulating excitatory amino acid transporters, and inhibiting insulin/insulin-like growth factor-1 (IGF-1), Wingless (Wnt), transforming growth factor-beta (TGF-ß), and retinoic-acid-inducible gene-I (RIG-I)/nuclear translocation of nuclear factor-κB (NF-κB) pathways. Stimulation and activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) and apoptosis signal-regulating kinase 1 (ASK1)/p38 mitogen­activated protein kinase (MAPK) signaling pathways could also be considered other possible antiseizure mechanisms of Kl. In the present review, the roles of Kl in the central nervous system as well as its possible anti-seizure properties are discussed for the first time.

Multicentricity in Different Molecular Subtypes of Breast Cancer: A Cross-sectional Study in Isfahan.

Background: Breast cancer is the most common cancer leading to death in women. Women with multicentric breast cancer were reported more likely to have poor prognosis. Here, we decided to study and compare the frequency distribution of multicentricity in different subtypes of breast cancer. Materials and Methods: This is a cross-sectional study that was performed in 2019-20 on medical records and breast pathology reports of 250 patients who undergone mastectomy due to breast cancer. Demographic data of all patients including age, along with other medical data such as menstruation condition, breast cancer grade, multicentricity status, stage, and expression of estrogen receptor (ER), progesterone (PR), and human epidermal growth factor receptor 2 (HER2) receptors were collected from medical records. Samples were divided into four subtypes of Luminal B, Luminal A, HER2 expressing, and basal-like. Results: The mean age of patients was 50.21 ± 11.15 years. Ninety-five patients (38%) had multicentricity and HER2 expressing (48.5%) and Luminal A (41.4%) were most common in patients with multicentricity. In addition, basal-like group presented with least multicentricity (13.5%) among the subtypes (P = 0.008). We also showed significant increased chances of multicentricity in Luminal B (odds ratio [OR] = 3.782) (P = 0.033), Luminal A (OR = 5.164) (P = 0.002), and HER2-expressing group (OR = 5.393) (P = 0.011). Conclusions: Taken together, we showed significantly increased chances of multicentricity in patients with HER2-expression, Luminal A, and Luminal B groups compared to basal-like group or triple negative. These results were in line with most previous studies; however, we showed higher rates of multicentricity among our population compared to some previous reports.

The effects of ketogenic diet on beta-hydroxybutyrate, arachidonic acid, and oxidative stress in pediatric epilepsy.

The exact mechanism of a ketogenic diet (KD) as a suitable alternative therapeutic approach for drug-resistant epilepsy (DRE) in alleviating seizures is not yet fully understood. The present study aimed to evaluate the role of the KD in reducing oxidative stress (OS) by increasing the ketone body beta-hydroxybutyrate (BHB) and Arachidonic acid (ARA), an essential polyunsaturated fatty acid, as a possible mechanism in relieving seizure attacks in children with DRE. Forty children with refractory epilepsy were included in the present study. The serum levels of BHB, ARA, and OS markers, malondialdehyde (MDA), and 8-hydroxyl-deoxyguanosine (8-OHdG), were evaluated in children with DRE and compared before and after the three months of KD therapy. Thirty-four of 40 included children could complete the three-month KD therapy. Twenty-one (61.76%) patients had more than a 50% reduction in seizure frequency after the KD (responders). The remaining 13 children were considered non-responders to the diet. The serum levels of ARA and BHB significantly (p < 0.05) increased after the KD therapy. The serum levels of OS parameters MDA and 8-OHdG before the diet therapy were significantly (p < 0.05) higher than those after the administration. The serum levels of BHB and MDA after the KD therapy in the responders were respectively higher and lower than those in the non-responders (p < 0.001). Ketogenic diet might reduce brain OS by increasing BHB and ARA. The role of BHB in diminishing OS and seizure might be more remarkable than ARA.

Total hip arthroplasty revision etiologies: a cross-sectional study in Isfahan, Iran.

Background: Complications after primary total hip arthroplasty (THA) are the most common reason for revision. Due to the high prevalence of revision surgery, we investigated the frequency of postprimary THA complications and related risk factor revision surgery. Materials and Methods: This is a cohort study that was performed in 2011-2019 on all patients who underwent primary THA surgery re-admitted to the Kashani and Saadi Hospital affiliated to Isfahan University of Medical Science, Iran, due to some complications after THA. Demographic and basic data were collected from patient's medical documents. Harris hip score (HHS) was calculated for all patients 6 months after the last surgery. The obtained data were analyzed using SPSS software version 21. Appropriate statistical tests were conducted to compare the results between the study groups. Results: Among 1260 patients who underwent primary THA, 1006 of them entered the study after applying the exclusion criteria. Thirty nine patients were under revision, 53.8% had prosthesis infection, 56.4% had instability, 6% had aseptic loosening, and 30.8% had periprosthetic fracture. Odds ratio for the above complications were 45.5, 45, 6.4, and 15.5, respectively. HHS postoperatively was also significantly (P < 0.001) higher in patients without revision. No correlation between gender or surgeon experience and revision was detected; however wound discharge (P < 0.001), body mass index (BMI) (P = 0.003), and Infection during hospitalization (P < 0.001) affect revision rate significantly. All four postsurgery complications, i.e., instability, postoperative prothesis infections, periprosthetic fractures, and aseptic loosening, significantly increased the risk of revision (P < 0.001, for all). Conclusion: Instability, prosthetic infections, periprosthetic fractures, and aseptic loosening were the most common causes for increasing revision rates after THA, respectively. Higher BMI, persistent wound discharge, and nosocomial infections during the first hospitalization also increased the rate of revision after primary THA.

Comparison of the Performance of Iranian Azeri-Speaking Children Based on Iran and Reference Bayley III Norms.

Objectives: The present study aimed to compare the performance of Iranian Azeri-speaking children based on Iran and the reference of the Bayley Scales of Infant and Toddler Development Third Edition (Bayley III) norms. Materials & Methods: The total sample included 248 infants and toddlers aged 16 days to 42 months and 15 days. The Iranian version of the Bayley III scale was used in this study. The scaled scores and composite scores in cognitive, language, and motor domains were compared based on Iran and reference Bayley III norms. Then, the proportions of children scoring < -1 standard deviation (SD) and < -2 SD were compared based on the two norms. Results: The scaled scores of the study group were higher based on the reference norms in receptive communication, fine motor, and gross motor subtests. The scaled scores were variable in expressive communication and cognitive subtests. The differences were significant for receptive communication and fine motor subtests (P<0.05). Using the reference norms instead of Iran norms resulted in under-referral regarding receptive communication and fine motor subtests. More children scored below 1 and 2 SD using Iran norms in comparison to those reported for using the reference norms. Conclusion: Iran norms differ significantly from the reference norms over two subscales. It is recommended to use population-specific norms to identify children with developmental delay and early intervention.

Hearing loss among patients with multiple sclerosis (PwMS): A systematic review and meta-analysis.

BACKGROUND: Multiple sclerosis (MS) is a kind of autoimmune disorder that has swept more than 2 million people worldwide and has caused multiple disabilities in the patients. Hearing loss(HL) is also one of the disabilities that numerous patients with multiple sclerosis (PwMS) experience. METHODS: We searched four databases: PubMed (Medline), Scopus, Web of Science, and Embase, from 1970 to July 2021. The gray literature containing the conference abstracts, review studies, and references of the articles was also investigated. We included any studies that reported PwMS with HL. RESULTS: Out of 1875 articles, 1042 articles remained following eliminating duplicates. Afterward, all articles were screened, and 953 were eliminated based on exclusion criteria. Full texts of 89 articles were collected. Finally, eight articles were selected based on inclusion and exclusion criteria. The pooled prevalence of HL in PwMS was 1.1% (95% CI: [0.2%, 2.4%]; I2=80.11%; p<0.001) among 5187 MS population. CONCLUSION: Our analysis suggests that MS might increase the risk of HL , and it might be an indicator for MS diagnosis. More research with larger sample sizes is required.

Pruritus-reducing effects of omega-3 fatty acids in hemodialysis patients: A cross-over randomized clinical trial.

INTRODUCTION: Chronic kidney disease-associated pruritus is a common complication in patients with end-stage renal disease. In this study, we have explored the outcome of omega-3 supplementary intake for the treatment of this symptom. METHODS: This double-blinded, randomized, crossover study was conducted in two dialysis centers in which 40 hemodialysis patients suffering from pruritus were randomly assigned into two groups (Group A and Group B). Patients in Group A consumed omega-3 capsules for 4 weeks and after a washout period (6 weeks), they took placebo for another 4 weeks. The same was performed in Group B but in the reverse order. Pruritus score was determined at the baseline, Week 4, 10, and 14. Serum levels of prostaglandin E2 were also recorded at the baseline and Week 4. RESULTS: There was a statistically significant reduction of pruritus score in patients who took the omega-3 fatty acid supplement. The mean pruritus score decreased significantly in both first (-3.41 ± 2.62, p < 0.001) and second (-1.00 ± 1.84, p = 0.04) treatment period after omega-3 treatment; but no significant mean pruritus score difference in placebo group after both intervention periods was observed. The decrease in prostaglandin E2 amount was not statistically significant in the intervention (omega-3) group compared to the placebo group (p = 0.204). DISCUSSION: Our observations indicate that omega-3 fatty acids (3 grams per day) have decreasing effects on pruritus. Also, reduction in prostaglandin E2 levels in the omega-3 group did not differ from the changes in the placebo group.

The clinical and paraclinical manifestations of tuberous sclerosis complex in children.

Tuberous sclerosis complex (TSC) is an autosomal-dominant, multi-system, neurocutaneous disorder characterized by hamartomas in multiple organs. This study aimed to evaluate the clinical and paraclinical manifestations of children with TSC. The clinical and paraclinical characteristics of 79 children with TSC were evaluated and the possible correlations between the factors were calculated. Among the studied children which composed of 41 females (51.9%) and 38 males (48.1%), skin manifestations as hypopigmented macules as well as the brain involvement as cortical tubers in all (100%) cases, seizure in 74 (93.7%), and sub-ependymal nodules in 73 (92.4%) patients were the most common findings. The renal angiomyolipoma was diagnosed in 36 (70.6%) out of 51 patients. Subependymal giant cell astrocytoma in 25 (3/54%) out of 46 patients, retinal hamartoma in 15 (42.9%) out of 35 patients, and cardiac rhabdomyoma in 17 (41.3%) out of 46 patients were diagnosed. Furthermore, 50 (63.3%) out of 79 patients had psychological disorders that had a significant correlation with the prevalence of seizures (p = 0.002). Given the multi-systemic involvement of TSC, it is necessary that all organs of the patients even without any related clinical symptom or sign be examined regularly for proper therapeutic intervention and prevent disease progression. The growth of hamartomas in the brain and kidneys can be life-threatening; therefore, these organs have more importance to be regularly followed up and examined.

Does cosmetic rhinoplasty affect sleep quality and/or contribute to the development of obstructive sleep apnea?

OBJECTIVE: Rhinoplasty can reduce nasal airways' resistance. This study evaluates the effects of rhinoplasty on sleep quality, daytime drowsiness, and obstructive sleep apnea (OSA). METHODS: In this prospective cohort study, 80 rhinoplasty candidates were examined before and six months after rhinoplasty to evaluate symptom changes. STOP-BANG, Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS) questionnaires, and nocturnal polysomnography were used, respectively, to screen for OSA, assess sleep quality, assess daytime drowsiness, and confirm results. RESULTS: Seventeen men (21.2%) and 63 women (78.8%) were studied. PSQI results showed an increase only in post-operative sleep disturbance items (p = 0.04). STOP-BANG showed an increase in apnea (p = 0.06) and a decrease in snoring (p = 0.06), which were both insignificant. The polysomnography tests confirmed the results of the questionnaires. CONCLUSION: Contrary to popular belief, rhinoplasty does not increase snoring, sleep disorders, or apnea.

A Case of Accidentally Found Gastrointestinal Stromal Tumor in a 57-Year-Old Candidate of Gastric Bypass Surgery.

INTRODUCTION: GIST tumors are the most common mesenchymal tumors in the alimentary tract but are rather rare compared to other GI tract tumors and are usually found incidentally. Studies about cases of GIST tumor in bariatric surgery are scarce and there is no specific guideline for treatment. Most of previous cases were managed by sleeve gastrectomy due to their location which were usually in the body and greater curvature. METHODS: This patient had a GIST on lesser curvature and therefore underwent laparoscopic Roux-en-Y bypass. The follow-up was done with imaging studies and CT scan since the location of the tumor was no longer accessible to endoscopy after the gastric bypass. RESULTS: The post-operative course was uneventful and after 2 years the patient is still in good health and had no other complications. The patient has been followed up by imaging studies. DISCUSSION: There are pros and cons to this compared with sleeve gastrectomy. The most important advantage for this approach is that we have the stomach preserved; thus, our operation has the reversibility potential in case of any complication which requires revision operations. However, on the flip side, the limitation of such intervention is that we are not able to use the EGD to monitor and follow up our patient. Based on the relevant literature, for following up and monitoring the postoperative condition of these patients with relatively small GISTs, imaging studies specially abdominal computed tomography scan (CT scan) would be highly beneficial. It is also worth of mentioning that performing a EGD before a bariatric surgery, which is well noted in IFSO position statements and is well explained and discussed in other literature, had a major role in diagnosing this patient's GIST tumor and is proved to be beneficial and essential, once again.

The Therapeutic Applications of Exosomes in Different Types of Diseases: A Review.

Exosomes are nano-sized vesicles secreted by nearly all cells and have received massive attention recently. In addition to their roles in pathophysiological processes and diagnostic evaluations, recently, several studies have applied exosomes to design novel therapeutic applications. Exosomes can be derived from a variety of cells and tissues and based on the source, they can carry different native contents such as DNAs, non-coding small RNAs, mRNAs, and proteins. They can also be engineered by adding desirable agents including specific biomolecules or drugs. Both forms can be therapeutically used for delivering their cargoes to the target cells and desirably alter their functions. The present study aimed to provide a comprehensive review of the various studies which applied exosomes as a therapeutic tool in the treatment of different types of diseases including cancer, cardiovascular, neurologic, psychiatric, liver, and kidney diseases.

The efficacy comparison of classic ketogenic diet and modified Atkins diet in children with refractory epilepsy: a clinical trial.

Dietary therapy has an important role in the therapeutic process in children suffering refractory epilepsy. There are two kinds of dietary therapy which are the most common in children with refractory epilepsy: The classic ketogenic diet (KD) and the modified Atkins diet (MAD). The purpose of the present study was to compare the efficacy, tolerability, and compliance of these two dietary therapies in the children who have refractory epilepsy during 6 months of treatment. From March 2017 to November 2018, 45 children aged 2-15 years who had refractory epilepsy were randomly allocated in KD or MAD group. The intervention period was 6 months in both groups. The frequencies of seizures were determined from parental reports and were compared between the groups. The patients with upper than 50% reduction in seizure frequency were deemed as responders to the diets. Twenty-four patients were assigned to the KD and 11 patients to the MAD. Overall, 45.8% of children treated with the KD and 45.5% of children treated with MAD had over than 50% response to the diet therapies. The difference was not statistically significant (P = 0.437). The MAD was more advantageous regarding better tolerability and fewer side effects. There is not much difference regarding the efficacy between the MAD and classic KD. The MAD with fewer side effects may be more suitable as the first line of dietary therapy in children with refractory epilepsy.

Ketogenic diet: overview, types, and possible anti-seizure mechanisms.

The ketogenic diet (KD) has been used for a long time as a therapeutic approach for drug-resistant epilepsy. It is a high-fat, low-carbohydrate, and adequate protein diet. There are various types of KD with some differences in their compositions that mainly include classic KD, medium-chain triglyceride diet, modified Atkins diet, and low glycemic index treatment. The anti-seizure mechanisms of KDs have not yet completely understood but, some possible mechanisms can be theorized. The aim of the present study was to review the various types of KD and explain the probable biochemical mechanisms involved in its anti-seizure property.

The Role of Infant Sex on Human Milk Composition.

Objective: Human milk (HM) is the most necessary and complete food for infants and their survival. It is a dynamic system influenced by different factors such as the sex of the infant. The study of the factors affecting the composition of mother's milk can provide us better insight into the nutritional needs of infants with different sex and improve the nutrition of babies who do not have access to HM. This study aimed to study the effects of infant sex on mother's milk composition. Methods: Sixty-one mother's milk samples were collected from mothers with female or male infants and divided into two (32 sons, 29 daughters) groups. The samples were analyzed by the Lacto-Scan milk analyzer and the obtained data were compared between the groups. Results: The results showed that the mean fat content in the milk samples of mothers with female infants (daughters group) (3.42 ± 1.80%) was significantly (p = 0.029) higher than that in mothers with male infants (sons group) (2.53 ± 1.18%). However, the sons group had higher (p = 0.024) levels of salts (0.76 ± 0.14%) compared with the daughters group (0.67 ± 0.18%). There was no significant (p > 0.05) difference in other indices between the groups. Conclusions: The sex of the infant is one of the important factors affecting the composition of mother's milk. The difference in the composition of mother's milk may reflect the differences in metabolic substrate needed for optimal growth and development in female and male infants.