Coenzyme Q10 ameliorates chemotherapy-induced cognitive impairment in mice: a preclinical study.

BACKGROUND: Among the three most used anticancer drugs, cyclophosphamide, Adriamycin, and 5-Fluorouracil (CAF), the most significant outcome is chemobrain, caused by increased oxidative stress, inflammatory insult, and mitochondrial dysfunction. OBJECTIVE: In this study, endogenous antioxidant coenzyme Q10 (CoQ10) was evaluated for its neuroprotective effects in CICI. MATERIALS AND METHODS: The chemobrain was induced in Swiss albino female mice by administering CAF (40 + 4 + 25 mg/kg) intraperitoneal (i.p.) in three cycles (single injection per week) followed by treatment with CoQ10 (40 mg/kg; p.o.) for up to 3 weeks followed by behavioral, biochemical, molecular and histopathological analysis. RESULTS: Treatment with CoQ10 significantly improved cognition by improving exploring time in novel objects recognition test followed by increasing the time spent in the target quadrant in MWM test as compared to CAF-treated animals. Moreover, CoQ10 demonstrated antioxidant properties by reducing the expression of LPO while increasing levels of GSH, SOD, and catalase as compared to CAF-treated animals. While the levels of AChEs were significantly reduced after CoQ10 treatment in CAF-treated animals. In terms of its mechanism, it effectively counteracted the pro-inflammatory substances (TNF-α and IL-1ß) triggered by CAF while also enhancing the levels of anti-inflammatory markers (IL-10 and Nrf2). Moreover, CoQ10 showed mitochondrial enhancers and it improved the level of Complex (I, II, and IV). Besides that, mitochondrial morphological analysis was done by TEM, and neuronal morphology along with quantification analysis was performed by H&E staining using Image J software to confirm the neuroprotective effect of CoQ10 over CAF-induced cognitive impairment. CONCLUSION: This study suggests CoQ10 can protect the mitochondria by imposing antioxidant, and anti-inflammatory properties, which could be a potential therapy for CICI.

In-vitro and in-vivo studies of two-drug cocktail therapy targeting chemobrain via the Nrf2/NF-κB signaling pathway.

Today, we critically need alternative therapeutic options for chemotherapy-induced cognitive impairment (CICI), often known as chemo brain. Mitochondrial dysfunction and oxidative stress are two of the primary processes that contribute to the development of chemobrain. Therefore, the purpose of this study was to investigate how CoQ10 and berberine shield neurons from chemotherapy-induced damage in in-vitro studies and memory loss in vivo studies. For the in-vitro investigation, we employed SH-SY5Y cell lines, and for the in-vivo study, we used female Swiss albino mice divided into seven different groups. Data from in-vitro studies revealed that treatment with coenzyme Q10 (CoQ10) and berberine improved chemotherapy-induced toxicity by reducing mitochondrial and total cellular ROS, as well as apoptosis-elicited markers (caspase 3 and 9). CoQ10 and berberine therapy inhibited the nuclear translocation of NF-κB and, consequently, the subsequent expressions of NLRP3 and IL-1ß, implying the prevention of inflammasome formation. Furthermore, CoQ10 and berberine therapy boosted Nrf2 levels. This is a regulator for cellular resistance to oxidants. The in vivo results showed that treatment with CoQ10 (40 mg/kg) and berberine (200 mg/kg) improved the behavioral alterations induced by CAF (40/4/25 mg/kg) in both the Morris Water Maze (MWM) and Novel Object Recognition (NOR) tests. Furthermore, biochemical and molecular evidence revealed the antioxidant, mitochondrial restorative, and anti-inflammatory potential of CoQ10 (40 mg/kg) and berberine (200 mg/kg) against CAF (40/4/25 mg/kg) subjected mice. In addition, the histological analysis using H&E staining and transmission electron microscopy (for mitochondrial morphology) showed that mice treated with the cocktails had an increased number of healthy neurons with intact mitochondria and a reduced presence of autophagic vacuoles in the hippocampal region of the brain. These findings back up our theory about this novel cocktail method for CAF-induced cognitive impairment.

Enhanced antichemobrain activity of amino acid assisted ferulic acid solid dispersion in adult zebrafish (Danio rerio).

Chemotherapy-induced cognitive impairment (CICI), also known as "chemobrain," is a common side effect of breast cancer therapy which causes oxidative stress and generation of reactive oxygen species (ROS). Ferulic acid (FA), a natural polyphenol, belongs to BCS class II is confirmed to have nootropic, neuroprotective and antioxidant effects. Here, we have developed FA solid dispersion (SD) in order to enhance its therapeutic potential against chemobrain. An amorphous ferulic acid loaded leucin solid dispersion (FA-Leu SD) was prepared by utilizing amino acid through spray-drying technique. The solid-state characterization was carried out via Fourier-transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and field emission scanning electron microscopy (FE-SEM). Additionally, in-vitro release studies and antioxidant assay were also performed along with in-vivo locomotor, biochemical and histopathological analysis. The physical properties showed that FA-Leu SD so formed exhibited spherical, irregular surface hollow cavity of along with broad melting endotherm as observed from FE-SEM and DSC results. The XRD spectra demonstrated absence of sharp and intense peaks in FA-Leu SD which evidenced for complete encapsulation of drug into carrier. Moreover, in-vitro drug release studies over a period of 5 h in PBS (pH 7.4) displayed a significant enhanced release in the first hr (68. 49 ± 5.39%) and in-vitro DPPH assay displayed greater antioxidant potential of FA in FA-Leu SD. Furthermore, the in-vivo behavioral findings of FA-Leu SD (equivalent to 150 mg/kg of free FA) exhibited positive results accompanied by in-vivo biochemical and molecular TNF-α showed a significant difference (p < 0.001) vis-à-vis DOX treated group upon DOX + FA-Leu SD. Additionally, histopathological analysis revealed neuroprotective effects of FA-Leu SD together with declined oxidative stress due to antioxidant potential of FA which was induced by anticancer drug doxorubicin (DOX). Overall, the above findings concluded that spray-dried FA-Leu SD could be useful for the treatment of chemotherapy induced cognitive impairment.

Polymer-mediated nanoformulations: a promising strategy for cancer immunotherapy.

Engineering polymer-based nano-systems have attracted many researchers owing to their unique qualities like shape, size, porosity, mechanical strength, biocompatibility, and biodegradability. Both natural and synthetic polymers can be tuned to get desired surface chemistry and functionalization to improve the efficacy of cancer therapy by promoting targeted delivery to the tumor site. Recent advancements in cancer immunoediting have been able to manage both primary tumor and metastatic lesions via activation of the immune system. The combinations of nano-biotechnology and immunotherapeutic agents have provided positive outcomes by enhancing the host immune response in cancer therapy. The nanoparticles have been functionalized using antibodies, targeted antigens, small molecule ligands, and other novel agents that can interact with biological systems at nanoscale levels. Several polymers, such as polyethylene glycol (PEG), poly(lactic-co-glycolic acid) (PLGA), poly(ε-caprolactone) (PCL), and chitosan, have been approved by the Food and Drug Administration for clinical use in biomedicine. The polymeric nanoformulations such as polymers-antibody/antigen conjugates and polymeric drug conjugates are currently being explored as nanomedicines that can target cancer cells directly or target immune cells to promote anti-cancer immunotherapy. In this review, we focus on scientific developments and advancements on engineered polymeric nano-systems in conjugation with immunotherapeutic agents targeting the tumor microenvironment to improve their efficacy and the safety for better clinical outcomes.

Role of Autophagy and Mitophagy in Neurodegenerative Disorders.

Autophagy is a self-destructive cellular process that removes essential metabolites and waste from inside the cell to maintain cellular health. Mitophagy is the process by which autophagy causes disruption inside mitochondria and the total removal of damaged or stressed mitochondria, hence enhancing cellular health. The mitochondria are the powerhouses of the cell, performing essential functions such as ATP (adenosine triphosphate) generation, metabolism, Ca2+ buffering, and signal transduction. Many different mechanisms, including endosomal and autophagosomal transport, bring these substrates to lysosomes for processing. Autophagy and endocytic processes each have distinct compartments, and they interact dynamically with one another to complete digestion. Since mitophagy is essential for maintaining cellular health and using genetics, cell biology, and proteomics techniques, it is necessary to understand its beginning, particularly in ubiquitin and receptor-dependent signalling in injured mitochondria. Despite their similar symptoms and emerging genetic foundations, Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) have all been linked to abnormalities in autophagy and endolysosomal pathways associated with neuronal dysfunction. Mitophagy is responsible for normal mitochondrial turnover and, under certain physiological or pathological situations, may drive the elimination of faulty mitochondria. Due to their high energy requirements and post-mitotic origin, neurons are especially susceptible to autophagic and mitochondrial malfunction. This article focused on the importance of autophagy and mitophagy in neurodegenerative illnesses and how they might be used to create novel therapeutic approaches for treating a wide range of neurological disorders.

Online Interest for Electronic Cigarettes Using Google Trends in the UK: A Correlation Analysis.

BACKGROUND: Google Trends provides an easily accessible and cost-effective method of providing real-time insight into user interest. OBJECTIVE: to address the gap in UK prevalence data for e-cigarettes by analyzing Google Trends to identify correlations with official data from Action on Smoking and Health. The study further evaluates Google Trend's sensitivity to real-time events and the ability for predictive models to forecast future data based on Google Trends. METHODS: UK Google Trends data from 2012 to 2021 was analyzed to assess (a) the most popular electronic nicotine device terminology; (b) statistically significant points in time; (c) correlations between Relative Search Volumes and official reports on electronic cigarette use and (d) whether Google Trends could predict future patterns in data. These were achieved using Locally Weighted Scatterplot Smoothing regression, Pruned Exact Linear Time Method, cross correlation, and Autoregressive Integrated Moving Average algorithms respectively. RESULTS: "Vape" was revealed to be the most popular electronic nicotine device terminology with a correlation coefficient greater than +0.9 when compared to official electronic cigarette consumption data within a one-year timescale (lag 0). Results from ARIMA modeling were varied with the algorithms forecasted trends line occasionally lying outside of a 95% prediction interval. CONCLUSION: Google Trends may correspond to population-based prevalence of electronic cigarette use. The changing trends coincide with changing policy decisions. Google Trends based prediction for online interest in electronic cigarettes requires further validation so should currently be used in conjunction with other traditional methods of data collections.

Transient Receptor Potential (TRP) based polypharmacological combination stimulates energy expending phenotype to reverse HFD-induced obesity in mice.

BACKGROUND & AIM: Obesity is a worldwide epidemic leading to decreased quality of life, higher medical expenses and significant morbidity. Enhancing energy expenditure and substrate utilization in adipose tissues through dietary constituents and polypharmacological approaches is gaining importance for the prevention and therapeutics of obesity. An important factor in this regard is Transient Receptor Potential (TRP) channel modulation and resultant activation of "brite" phenotype. Various dietary TRP channel agonists like capsaicin (TRPV1), cinnamaldehyde (TRPA1), and menthol (TRPM8) have shown anti-obesity effects, individually and in combination. We aimed to determine the therapeutic potential of such combination of sub-effective doses of these agents against diet-induced obesity, and explore the involved cellular processes. KEY FINDINGS: The combination of sub-effective doses of capsaicin, cinnamaldehyde and menthol induced "brite" phenotype in differentiating 3T3-L1 cells and subcutaneous white adipose tissue of HFD-fed obese mice. The intervention prevented adipose tissue hypertrophy and weight gain, enhanced the thermogenic potential, mitochondrial biogenesis and overall activation of brown adipose tissue. These changes observed in vitro as well as in vivo, were linked to increased phosphorylation of kinases, AMPK and ERK. In the liver, the combination treatment enhanced insulin sensitivity, improved gluconeogenic potential and lipolysis, prevented fatty acid accumulation and enhanced glucose utilization. SIGNIFICANCE: We report on the discovery of therapeutic potential of TRP-based dietary triagonist combination against HFD-induced abnormalities in metabolic tissues. Our findings indicate that a common central mechanism may affect multiple peripheral tissues. This study opens up avenues of development of therapeutic functional foods for obesity.

The Role of Mitophagy in Various Neurological Diseases as a Therapeutic Approach.

Mitochondria are critical to multiple cellular processes, from the production of adenosine triphosphate (ATP), maintenance of calcium homeostasis, synthesis of key metabolites, and production of reactive oxygen species (ROS) to maintain necrosis, apoptosis, and autophagy. Therefore, proper clearance and regulation are essential to maintain various physiological processes carried out by the cellular mechanism, including mitophagy and autophagy, by breaking down the damaged intracellular connections under the influence of various genes and proteins and protecting against various neurodegenerative diseases such as Parkinson disease (PD), amyotrophic lateral sclerosis (ALS), Alzheimer disease (AD), and Huntington disease (HD). In this review, we will discuss the role of autophagy, selective macroautophagy, or mitophagy, and its role in neurodegenerative diseases along with normal physiology. In addition, this review will provide a better understanding of the pathways involved in neuron autophagy and mitophagy and how mutations affect these pathways in the various genes involved in neurodegenerative diseases. Various new findings indicate that the pathways that remove dysfunctional mitochondria are impaired in these diseases, leading to the deposition of damaged mitochondria. Apart from that, we have also discussed the therapeutic strategies targeting autophagy and mitophagy in neurodegenerative diseases. The mitophagy cycle results in the degradation of damaged mitochondria and the biogenesis of new healthy mitochondria, also highlighting different stages at which a particular neurodegenerative disease could occur.

Characterization of oleosin genes from forage sorghum in Arabidopsis and yeast reveals their role in storage lipid stability.

MAIN CONCLUSION: Overexpression of forage sorghum oleosin genes in Arabidopsis oleosin-deficient mutant and yeast showed increased germination rate, triacylglycerol content, and protection against lipase-mediated TAG degradation. Plant lipids are an important source of ration for cattle or other livestock animals to fulfil their energy needs. Poor energy containing green forages are still one of the major sources of food for livestock animals, leaving the animals undernourished. This lowers the milk and meat production efficiency, thereby affecting human consumption. Oleosin, an essential oil body surface protein, is capable of enhancing and stabilizing the lipid content in plants. We identified and functionally characterized three forage sorghum oleosin genes (SbOle1, SbOle2, and SbOle3) in Arabidopsis and yeast. Phylogenetic analysis of SbOle proteins showed a close relationship with rice and maize oleosins. Expression analysis of SbOle genes determined a higher expression pattern in embryo followed by endosperm, while its expression in the non-seed tissues remained negligible. Overexpression of SbOle genes in Arabidopsis ole1-deficient mutants showed restoration of normal germination whereas control mutant seeds showed lower germination rates. Heterologous overexpression of SbOle in yeast cells resulted in increased TAG accumulation. Additionally, the TAG turnover assay showed the effectiveness of SbOle genes in reducing the yeast endogenous and rumen bacterial lipase-mediated TAG degradation. Taken together, our findings not only provide insights into forage sorghum oleosin for increasing the energy content in non-seed organs but also opened up the direction towards implication of oleosin in rumen protection of fodders.

Use and interest of electronic nicotine delivery systems (ENDS): Assessing the validity of Google Trends.

Background: Initial evidence suggests a role for Google Trends (GT) in monitoring use and interest in Electronic Nicotine Delivery Systems (ENDS).Objective: To examine the validity of GT data for assessing population behavior and interest in ENDS.Methods: GT search, done from the US and India to assess: (a) whether descriptive and statistical trends of specific search words depicting online interest in ENDS were similar to the published reports on actual use of these products in the US; (b) correlations between state-wise relative search volumes (RSV) of these words and prevalence of ENDS use; (c) the change in the online interest of ENDS after change in its regulatory policy.Results: Locally weighted scatter plot analysis showed "electronic cigarette," "vaping," and "cigarette" trends mirrored the use trend reported by the US-based National Youth Tobacco Survey (2019). Online interest in "Juul pods" followed the trends of its use. Geo-spatial RSVs of "electronic cigarette" (r=0.74, p<0.0001) and "vaping" (r=0.55, p<0.0001) correlated positively with state-wise prevalence of switch to ENDS in adults. Complete ENDS use prohibition in India was associated with a decrease in the online interest in "electronic cigarettes" (t=3.18, p=0.01) and "vaping" (t=2.3, p=0.04). Regulation of use in New Mexico (USA) was associated with a reduction in "electronic cigarettes" (t=4.09, p=0.0005) but not in "vaping."Conclusion: GT may be used to validate existing information and assess the potential effect of ENDS regulations. Its role can also be extended for monitoring interest and use of other drugs and alcohol.

pH-Triggered, Synbiotic Hydrogel Beads for In Vivo Therapy of Iron Deficiency Anemia and Reduced Inflammatory Response.

Iron deficiency anemia (IDA) is the most common nutritional disorder worldwide nearly affecting two billion people. The efficacies of conventional oral iron supplements are mixed, intravenous iron administration acquaintances with finite but crucial risks. Usually, only 5-20% iron is absorbed in the duodenum while the remaining fraction reaches the colon, affecting the gut microbes and can significantly impact intestinal inflammatory responses. Therefore, administration of gut bacterial modulators such as probiotics, prebiotics, and any other dietary molecules that can stimulate healthy gut bacteria can enhance iron absorption without any adverse side effects. In this study, we have prepared an iron supplement to avoid the side effects of conventional oral iron supplements. The formulation includes co-encapsulation of iron with anti-inflammatory probiotic bacteria within alginate/starch hydrogels (B + I-Dex (H)), which has been demonstrated to be efficient in mitigating IDA in vivo. As intestinal pH increases, the pore size of hydrogel increases due to ionic interactions and thus releases the encapsulated bacteria and iron. The field emission scanning electron microscopy (FESEM) analysis confirmed the porous structure of hydrogel beads, and in vitro release studies showed a sustained release of iron and bacteria at intestinal pH. The hydrogel was found to be nontoxic and biocompatible in Caco2 cell lines. The formulation showed efficient in vitro and in vivo iron bioavailability in Fe depletion-repletion studies. B + I-Dex (H) was observed to generate less inflammatory response than FeSO4 or nonencapsulated iron dextran (I-Dex) in vivo. We entrust that this duly functional hydrogel formulation could be further utilized or modified for the development of oral therapeutics for IDA.

Long noncoding RNA NEAT1 mediates neuronal histone methylation and age-related memory impairment.

Histone methylation is critical for the formation and maintenance of long-term memories. Long noncoding RNAs (lncRNAs) are regulators of histone methyltransferases and other chromatin-modifying enzymes (CMEs), thereby epigenetically modifying gene expression. Here, we investigated how the lncRNA NEAT1 may epigenetically contribute to hippocampus-dependent, long-term memory formation using a combination of transcriptomics, RNA-binding protein immunoprecipitation, CRISPR-mediated gene activation (CRISPRa), and behavioral approaches. Knockdown of the lncRNA Neat1 revealed widespread changes in gene transcription, as well as perturbations of histone 3 lysine 9 dimethylation (H3K9me2), a repressive histone modification mark that was increased in the hippocampus of aging rodents. We identified a NEAT1-dependent mechanism of transcriptional repression by H3K9me2 at the c-Fos promoter, corresponding with observed changes in c-Fos mRNA expression. Overexpression of hippocampal NEAT1 using CRISPRa was sufficient to impair memory formation in young adult mice, recapitulating observed memory deficits in old adult mice, whereas knocking down NEAT1 in both young and old adult mice improved behavior test-associated memory. These results suggest that the lncRNA NEAT1 is an epigenetic suppressor of hippocampus-dependent, long-term memory formation.

Early experience with endoscopic lumbar sympathectomy for plantar hyperhidrosis.

OBJECTIVE: We describe our endoscopic lumbar sympathectomy technique and our early experience using it to treat plantar hyperhidrosis. METHODS: We reviewed 20 lumbar sympathectomies performed in our vascular unit for plantar hyperhidrosis in 10 patients from 2011 and 2014. Demographics and outcomes were analyzed and a review of the literature conducted. RESULTS: All procedures were carried out endoscopically with no intraoperative or postoperative morbidity. Plantar anhidrosis was achieved in all the patients, although two patients (20%) suffered a relapse. Unwanted side-effects occurred in the form of compensatory sweating in three patients (30%) and post-sympathectomy neuralgia in two patients (20%). None of the patients experienced sexual dysfunction. CONCLUSION: Management of plantar hyperhidrosis may be based upon a therapeutic ladder starting with conservative measures and working up to surgery depending on the severity of the disease. Minimally invasive (endoscopic) sympathectomy for the thoracic chain is well established, but minimally invasive sympathectomy for the lumbar chain is a relatively new technique. Endoscopic lumbar sympathectomy provides an effective, minimally invasive method of surgical management, but long-term data are lacking.

Preventive effect of N-acetyl-L-cysteine on oxidative stress and cognitive impairment in hepatic encephalopathy following bile duct ligation.

Oxidative stress caused by ammonia toxicity is known to play a key role in the pathogenesis of hepatic encephalopathy (HE). The present study was designed to evaluate the protective effect of N-acetyl-L-cysteine (NAC) supplementation in a bile duct ligation (BDL)-induced model of HE. Three weeks after BDL, rats developed biliary fibrosis which was supported by liver function tests, ammonia levels, and hydroxyproline content. Impaired cognitive and motor functions were observed along with decreased acetylcholinesterase activity in the brain of BDL rats. Cerebral cortex and cerebellum of BDL animals showed an increase in lipid peroxidation and reduction in total and nonprotein thiols along with reduction in antioxidant enzymes. Histopathological examination of cortex and cerebellum of BDL rats showed astrocytic swelling, inflammation, necrosis, and white matter edema. One week after BDL surgery, animals administered with NAC at a daily dose 100 mg/kg for 2 weeks showed significant improvement in the activity of liver marker enzymes and restored structural morphology of liver. NAC was able to ameliorate spatial memory and motor coordination deficits observed in BDL rats. NAC supplementation decreased lipid peroxidation and was also able to restore the activity of antioxidant enzymes as well as structural deficits observed in the cortex and cerebellum of BDL animals. The results clearly demonstrate that the protective effect of NAC in an experimental model of HE is mediated through attenuation of oxidative stress, suggesting a therapeutic role for NAC in individuals withHE.

Prairie voles as a novel model of socially facilitated excessive drinking.

Social relationships strongly affect alcohol drinking in humans. Traditional laboratory rodents do not exhibit social affiliations with specific peers, and cannot adequately model how such relationships impact drinking. The prairie vole is a socially monogamous rodent used to study social bonds. The present study tested the prairie vole as a potential model for the effects of social affiliations on alcohol drinking. Same-sex adult sibling prairie voles were paired for five days, and then either separated into individual cages, or housed in pairs. Starting at the time of separation, the voles received unlimited access to alcohol in a two-bottle choice test versus water. Pair-housed siblings exhibited higher preference for alcohol, but not saccharin, than singly housed voles. There was a significant correlation between the amount of alcohol consumed by each member of a pair when they were housed together (r = 0.79), but not when housed apart (r = 0.20). Following automated analysis of circadian patterns of fluid consumption indicating peak fluid intake before and after the dark phase, a limited access two-hour two-bottle choice procedure was established. Drinking in this procedure resulted in physiologically relevant blood ethanol concentrations and increased Fos immunoreactivity in perioculomotor urocortin containing neurons (but not in nucleus accumbens or central nucleus of the amygdala). The high ethanol preference and sensitivity to social manipulation indicate that prairie voles can serve to model social influences on excessive drinking.

Cosmetic tourism: public opinion and analysis of information and content available on the Internet.

BACKGROUND: The medical tourism market is a rapidly growing sector fueled by increasing health care costs, longer domestic waiting times, economic recession, and cheaper air travel. OBJECTIVES: The authors investigate public opinion on undergoing cosmetic surgery abroad and then explore the information patients are likely to encounter on the Internet when searching for such services. METHODS: A poll of 197 members of the general public was conducted in the United Kingdom. An Internet search including the terms plastic surgery abroad was conducted, and the first 100 relevant sites were reviewed. RESULTS: Of the 197 respondents, 47% had considered having some form of cosmetic surgery. Most (97%) would consider going abroad for their procedure. The Internet was a source of information for 70%. The review of the first 100 sites under "plastic surgery abroad" revealed that most centers were located in Eastern Europe (26%), South America (14%), and the Far East (11%). Exploring the information provided on the Web sites, we found 37% contained no information regarding procedures. Only 10% of sites contained any information about potential complications. Even less frequently mentioned (4%) were details of aftercare or follow-up procedures. CONCLUSIONS: The authors found that the overwhelming majority of respondents considering plastic surgery would also consider seeking cosmetic surgical treatment abroad. The Internet sites that appear most prominently in an online search contained a distinct lack of information for potential patients, particularly with regard to complications and aftercare. There is, therefore, a need for improved public awareness and education about the considerations inherent in medical tourism. The introduction of more stringent regulations for international centers providing such services should also be considered to help safeguard patients.