Evaluation of the Effects of Opium on the Expression of SOX2 and OCT4 in Wistar Rat Bladder.

BACKGROUND: Bladder cancer is a malignancy greatly affected by behavioral habits. The aim of this study was to examine the effect of opium on changes in the expression of OCT4 and SOX2 in the bladder tissue of rats. METHOD: Thirty six rats were divided into six groups: 24 rats in the addicted group received morphine and opium for 4 months with 12 rats in the control group. Blood testing was done for the evaluation of CBC, MDA, and TAC. The bladder tissue was removed and checked by histopathological examination. All total RNA was extracted, then cDNAs were synthesized and the OCT4 and SOX2 gene expressions were evaluated by Real-time PCR. RESULTS: The OCT4 mRNA expression level in the opium group of rats was significantly increased compared to the control group (13.5 and 6.8 fold in males and females respectively). Also, in the morphine group, similar augmentation was detected (3.8 and 6.7 fold in males and females respectively). The SOX2 mRNA over-expression level was seen in the morphine group of both genders as compared to the control group (3.7 and 4.2 fold in male and female respectively) but in the opium group, enhancement of mRNA level was seen only in males (6.6 fold). Opium increases both OCT4 and SOX2 expression more than morphine in male rats, but in female rats, SOX2 is increased more by morphine. CONCLUSION: Over expression of OCT4 and SOX2 was observed in rats treated with opium and morphine. Increased OCT4 and SOX2 expression was seen in opium-treated male rats, but in female rats, SOX2 was increased more by morphine.

Kidney cancer in the Middle East and North Africa region: a 30-year analysis (1990-2019).

Kidney cancer, a type of urogenital cancer, imposes a high burden on patients. Despite this, no recent research has evaluated the burden of this type of cancer in the Middle East and North Africa (MENA) region. This study explored the burden of kidney cancer from 1990 to 2019 according to age, sex and socio-demographic index (SDI). The Global Burden of Disease (GBD) 2019 data was utilized to estimate the incidence, death, and disability-adjusted life-years (DALYs) caused by kidney cancer. These estimates were reported as counts and as age-standardised rates with 95% uncertainty intervals (UIs). The estimated age-standardised incidence, mortality, and DALY rates of kidney cancer in 2019 were 3.2 (2.8-3.6), 1.4 (1.2-1.6), and 37.2 (32.0-42.6) per 100,000, respectively. Over the period from 1990 to 2019, these rates have increased by 98.0%, 48.9%, and 37.7%, respectively. In 2019, the United Arab Emirates, Qatar, and Lebanon had the largest age-standardised incidence, mortality, and DALY rates. The smallest age-standardised incidence rates were seen in Yemen, Afghanistan, and the Syrian Arab Republic. Additionally, the smallest age-standardised mortality and DALY rates were observed in the Syrian Arab Republic, Yemen, and Morocco. The highest incidence rates were found among individuals aged 75-79 in both males and females. In 2019, the MENA/Global DALY ratio exceeded one for females aged 5-19 age and males aged 5-14, compared to 1990age groups in males. The burden of kidney cancer consistently rose with increasing SDI levels from 1990 to 2019. The increasing burden of kidney cancer highlights the urgent need for interventions aimed at improving early diagnosis and treatment in the region.

The burden of schizophrenia in the Middle East and North Africa region, 1990-2019.

Schizophrenia ranks as the third-most common cause of disability among mental disorders globally. This study presents findings on the prevalence, incidence and years lived with disability (YLDs) as a result of schizophrenia in the Middle East and North Africa (MENA), stratified by age, sex and sociodemographic index (SDI). We collected publicly accessible data from the Global Burden of Disease (GBD) study 2019. This study reports the burden of schizophrenia, from 1990 to 2019, for the 21 countries that comprise MENA. In 2019, MENA exhibited an age-standardised point prevalence of 248.2, an incidence rate of 14.7 and an YLD rate of 158.7 per 100,000, which have not changed substantially between 1990 and 2019. In 2019, the age-standardised YLD rate was highest in Qatar and lowest in Afghanistan. No MENA countries demonstrated noteworthy changes in the burden of schizophrenia from 1990 to 2019. Furthermore, in 2019, the highest number of prevalent cases and the point prevalence were observed among those aged 35-39, with a higher prevalence among males in almost all age categories. Additionally, in 2019, the age-standardised YLD rates in MENA were below the worldwide average. Finally, there was a positive correlation between the burden of schizophrenia and the SDI from 1990 to 2019. The disease burden of schizophrenia has remained relatively stable over the past thirty years. Nevertheless, as the regional life-expectancy continues to increase, the burden of schizophrenia is also expected to rise. Therefore, early planning for the increase in the burden of the disease is urgently needed in the region.

The efficacy and safety of Nigella sativa in the management of osteoarthritis: A systematic review.

Background and Aims: Osteoarthritis (OA) is one of the most common debilitating diseases among the aging population. Nigella sativa is one potential treatment for OA. Here, we sought to evaluate the efficacy and safety of Nigella sativa for treating patients with OA. Methods: PubMed, Scopus, Embase, and Web of Science were searched up to October 20, 2022. The primary outcome was changes in the pain score after receiving Nigella sativa or control agents based on the results of randomized controlled trials (RCTs). The secondary outcome was set as the frequency of adverse events reported during the follow-up period. Results: Six RCTs involving a total of 370 patients with knee OA were included in the present systematic review. Among the four screened studies, the topical administration of Nigella sativa oil was found to be more effective than the placebo in relieving pain in three trials. Additionally, the oral use of Nigella sativa oil was assessed in two trials, and an improvement in pain score relative to placebo was documented in only one of the studies. Also, the trial that evaluated the effectiveness of Nigella sativa oral capsules did not demonstrate any difference in pain reduction between the intervention and placebo groups. Overall, either topical or oral administration of Nigella sativa was well tolerated, and no serious adverse events were reported. Conclusion: Nigella sativa is generally safe, but conflicting findings from low-quality studies hinder the ability to make clinical recommendations for or against treating OA. Robust trials are needed for informed decisions.

Immune checkpoint inhibitors in gastrointestinal malignancies: an Umbrella review.

In the Modern era, immune checkpoint inhibitors (ICIs) have been the cornerstone of success in the treatment of several malignancies. Despite remarkable therapeutic advances, complex matrix together with significant molecular and immunological differences have led to conflicting outcomes of ICI therapy in gastrointestinal (GI) cancers. As far we are aware, to date, there has been no study to confirm the robustness of existing data, and this study is the first umbrella review to provide a more comprehensive picture about ICIs' efficacy and safety in GI malignancies. Systematic search on PubMed, Scopus, Web of Science, EMBASE, and Cochrane library identified 14 meta-analyses. The pooled analysis revealed that ICIs application, especially programmed death-1 (PD-1) inhibitors such as Camrelizumab and Sintilimab, could partially improve response rates in patients with GI cancers compared to conventional therapies. However, different GI cancer types did not experience the same efficacy; it seems that hepatocellular carcinoma (HCC) and esophageal cancer (EC) patients are likely better candidates for ICI therapy than GC and CRC patients. Furthermore, application of ICIs in a combined-modal strategy are perceived opportunity in GI cancers. We also assessed the correlation of PD-L1 expression as well as microsatellite status with the extent of the response to ICIs; overall, high expression of PD-L1 in GI cancers is associated with better response to ICIs, however, additional studies are required to precisely elaborate ICI responses with respect to microsatellite status in different GI tumors. Despite encouraging ICI efficacy in some GI cancers, a greater number of serious and fatal adverse events have been observed; further highlighting the fact that ICI therapy in GI cancers is not without cost, and further studies are required to utmost optimization of this approach in GI cancers.

Efficacy and safety of immune checkpoint inhibitors for patients with prostate cancer: a systematic review and meta-analysis.

Immunotherapy has revolutionized the treatment paradigm of many cancers, however, its effectiveness in prostate cancer patients is still under question. In the present systematic review and meta-analysis, we sought for assessing the efficacy and safety of Immune checkpoint inhibitors (ICIs) in patients with prostate cancer. PubMed, Scopus, Web of Science, and EMBASE databases were searched on Aguste 19, 2022. Thirty five studies met the eligibility criteria. The median overall survival (mOS) of all treatments was 14.1 months, with the longest and shortest mOS was seen among patients who received anti-CTLA-4 monotherapy and anti-PD-1/PD-L1+anti-CTLA-4 regimen at 24.9 and 9.2 months, respectively. Noteworthy, all types of adverse events had the lowest incidence in the anti-PD-1/PD-L1 monotherapy group. Considering the ICI monotherapy regimens, we found that fatigue, diarrhea, and infusion reaction had the highest incidence rates. Future studies evaluating the efficacy and safety of novel combination therapies with ICIs are warranted.

Cerebrospinal fluid biomarkers profile in scans without evidence of dopaminergic deficits (SWEDD).

Background: A small proportion of patients with clinical parkinsonism have normal transporter-single photon emission computed tomography (DaTSPECT) which is commonly defined as scans without evidence of dopaminergic deficits (SWEDD). A better understanding of SWEDD can improve the current therapeutic options and appropriate disease monitoring. Aim: We aimed to assess CSF biomarkers levels including α-synuclein (α-syn), amyloid ßeta (Aß1-42), total tau (t-tau), and phosphorylated tau (p-tau) in SWEDD and investigate the longitudinal alteration in the CSF profile. Methods: In total, 406 early-stage PD, 58 SWEDD, and 187 healthy controls (HCs) were entered into our study from PPMI. We compared the level of CSF biomarkers at baseline, six months, one year, and two years. Furthermore, the longitudinal alteration of CSF biomarkers was explored in each group using linear mixed models. Results: There was no significant difference in the level of CSF α-syn Aß1-42, t-tau, and p-tau between HCs and SWEDD at different time points. Investigating the level of CSF α-syn in PD and SWEDD showed a significant difference at one (p = 0.016) and two years (p = 0.006). Also, we observed a significant difference in the level of CSF Aß1-42 between SWEDD and PD at one year (p = 0.012). Moreover, there was a significant difference in the level of CSF t-tau between SWEDD and PD subjects at one (p = 0.013) and two years (p = 0.017). Furthermore, there was a significant difference in the level of CSF p-tau between SWEDD and PD groups at two years visits (p = 0.030). Longitudinal analysis showed a significant decrease after one (p = 0.029) and two years (p = 0.002) from baseline in the level of CSF α-syn only in the PD group. Also, we observed that the level of CSF Aß1-42 significantly increased after one year in SWEDD (p = 0.031) and decreased after two years from baseline in PD subjects (p = 0.005). Moreover, there was a significant increase in the level of CSF t-tau after two years (p = 0.036) and CSF p-tau after six months from baseline in SWEDD subjects (p = 0.011). Conclusion: This finding suggests a faster neurodegeneration process in PD patients compared to SWEDD at least based on these biomarkers. Future studies with longer follow-up duration and more sample sizes are necessary to validate our results.

Clostridioides difficile PCR ribotypes 001 and 084 can trigger autophagy process in human intestinal Caco-2 cells.

Autophagy is a homeostatic process that can promote cell survival or death. However, the exact role of autophagy in Clostridioides difficile infection (CDI) is still not precisely elucidated. Here, we investigate the role of distinct C. difficile ribotypes (RTs) in autophagy induction using Caco-2 cells. The expression analysis of autophagy-associated genes and related miRNAs were examined following treatment of Caco-2 cells with C. difficile after 4 and 8 h using RT-qPCR. Toxin production was assessed using enzyme-linked immunosorbent assay (ELISA). Immunofluorescence analysis was performed to detect MAP1LC3B/LC3B, followed by an autophagic flux analysis. C. difficile significantly reduced the viability of Caco-2 cells in comparison with untreated cells. Elevated levels of LC3-II and SQSTM1/p62 by C. difficile RT001 and RT084 in the presence of E64d/leupeptin confirmed the induction of autophagy activity. Similarly, the immunofluorescence analysis demonstrated that C. difficile RT001 and RT084 significantly increased the amount of LC3-positive structures in Caco-2 cells. The induction of autophagy was further demonstrated by increased levels of LC3B, ULK1, ATG12, PIK3C3/VPS34, BECN1 (beclin 1), ATG5, and ATG16L1 transcripts and reduced levels of AKT and MTOR gene expression. The expression levels of MIR21 and MIR30B, microRNAs that suppress autophagy, were differentially affected by C. difficile. In conclusion, the present work revealed that C. difficile bacteria can induce autophagy through both toxin-dependent and -independent mechanisms. Also, our results suggest the potential role of other C. difficile virulence factors in autophagy modulation using intestinal cells in vitro.

The burden of neck pain in the Middle East and North Africa region, 1990-2019.

Background: Neck pain is a common cause of disability across the world. The objective of the present study was to present a thorough investigation of the burden caused by neck pain in the Middle East and North Africa (MENA) region, by country, sex, age group and socio-demographic index (SDI). Methods: The data on the burden of neck pain, encompassing its prevalence, incidence and years lived with disability (YLDs), were extracted from the Global Burden of Disease (GBD) 2019 study. These findings are reported as age-standardised numbers and rates (per 100,000), accompanied by 95 % uncertainty intervals (UIs). Results: The age-standardised point prevalence of neck pain in 2019 was 3066.7 (95 % UI: 2407.8 to 3894.3) per 100,000, with an age-standardised incidence rate of 649.2 (509.2-829.2) in the MENA region, neither of which have changed since 1990. The age-standardised YLD rate of neck pain was 303.0 (201.5-438.8) per 100,000 population in 2019. The highest YLD rate of neck pain was found in Iran [423.5 (280.3-609.8)] and the lowest in Kuwait [215.0 (141.0-314.1)]. The highest number of prevalent cases were seen in the 45-49 age-group for both sexes in 2019, but overall females had a higher point prevalence than males. Furthermore, over the study period (1990-2019) there was no clear and consistent relationship between the SDI and the burden of neck pain. Conclusion: Although the burden of neck pain has largely remained stable over the past three decades, the prevalence and morbidity in the MENA region remains high. Preventive and rehabilitative programs should be implemented that firstly target middle-aged females and males.

Corrigendum to "Helicobacter pylori infection contributes to the expression of Alzheimer's disease-associated risk factors and neuroinflammation" [Heliyon 9(9) (September 2023) e19607].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e19607.].

Helicobacter pylori infection contributes to the expression of Alzheimer's disease-associated risk factors and neuroinflammation.

Over time, mounting evidence has demonstrated extra-gastric manifestations of Helicobacter pylori infection. As such, a number of studies demonstrated the potential contribution of H. pylori infection to the incidence and progression of Alzheimer's disease (AD). Considering unanswered questions regarding the effect of H. pylori infection on brain activity, we sought to investigate the impact of H. pylori infection on the expression of AD-associated risk factors. We used two H. pylori clinical strains obtained from two patients with peptic ulcer and evaluated their influence on the expression level of AD-associated genes (APP, ApoE2, ApoE4, ABCA7, BIN1, Clu, CD33) and genes for inflammatory markers (TLR-4, IL-8, TNF-α) by RT-qPCR in human glioblastoma (U87MG) and astrocyte (1321N1) cell lines. The expression of inflammatory cytokines was further assessed by ELISA assay. The exposure of U97MG and 1321N1 cells to H. pylori strains resulted in a significant enhancement in the expression level of the risk allele ApoE4, while reducing the expression of the protective allele ApoE2. H. pylori infection remarkably increased the expression level of main AD-associated risk genes, and also pro-inflammatory cytokines. Furthermore, we noticed a substantial elevation in the mRNA expression level of transmembrane receptor TLR-4 following H. pylori infection. Our findings presented the potential for H. pylori to stimulate the expression of AD-associated risk genes and trigger neuroinflammation in the brain tissue. This, in principle, leads to the recommendation that AD patients should perhaps test for H. pylori infection and receive treatments upon positive detection.

The burden of rheumatic heart disease in the Middle East and North Africa region, 1990-2019.

BACKGROUND: Rheumatic heart disease (RHD) is a treatable and preventable condition resulting from acute rheumatic fever. AIM: To report the prevalence, mortality and disability-adjusted life-years (DALY) due to RHD in the Middle East and North Africa (MENA) region from 1990 to 2019, by sex, age group, country and sociodemographic index (SDI). METHODS: Information on the prevalence, mortality and DALY associated with RHD were obtained from the Global Burden of Disease Study 2019. Data were gathered for all countries in the MENA region over the period 1990-2019. These data included counts and age-standardized rates per 100,000, accompanied by 95% uncertainty intervals (UIs). RESULTS: The MENA region had an age-standardized point prevalence of 388.9 per 100,000 in 2019, which was 5.4% higher than in 1990. The annual incidence rate was 1.6, which was 63.4% lower than in 1990. There were 379.4 thousand DALY attributable to RHD in 2019, with an age-standardized rate of 67.1, which was 61.3% lower than in 1990. In 2019, an estimated 7.4 thousand deaths were due to RHD, and the age-standardized death rate was 63.4% lower in 2019 than in 1990. DALY rates rose steadily with increasing age in both males and females. The SDI correlated negatively with the rate of DALY for RHD throughout the study period. CONCLUSION: The burden of RHD in MENA declined from 1990 to 2019, demonstrating the importance of regularly updating health data and identifying risk factors, and developing effective guidelines on prevention.

The effects of olive oil consumption on cognitive performance: a systematic review.

Introduction: The Mediterranean diet is marked by the regular intake of olive oil, which may play a role in preventing and protecting against cognitive deterioration and dementia. The strength of these effects have been examined by several recent randomized controlled trials (RCTs), but their findings have not been consistent. In light of this inconsistency, the present study performed a systematic review to examine the relationship between the consumption of olive oil and cognition. Methods: The Web of Science, Scopus, PubMed, and Google Scholar were systematically searched up to August 11, 2023. The review included RCTs, cross-sectional studies, cohort studies and case-control studies that explored the impact of olive oil consumption on cognitive performance among those older than 55 years old. Studies were excluded if they employed a design other than those mentioned above, involved participants under 55 years old, or did not specifically examine the cognitive effects of olive oil consumption. The quality of the included studies were measured using the Cochrane risk-of-bias tool and the Newcastle Ottawa Scale checklists. Results: Eleven studies were identified, which were comprised of four cross-sectional studies, four prospective cohort studies and three RCTs. The cohort studies and RCTs consistently found that olive oil consumption had a favorable effect on cognitive performance across a number of cognitive domains over time. Similarly, all of the cross-sectional studies reported that the consumption of olive oil was positively associated with cognitive health. Conclusion: The consumption of olive oil was found to enhance cognitive functioning and to reduce cognitive decline. Further large-scale investigations are required to strengthen this conclusion.

The burden of vision loss in the Middle East and North Africa region, 1990-2019.

BACKGROUND: The loss of vision is a substantial public health concern that has important implications for an individual's quality of life. The primary objective of this research was to document the burden of vision loss in the Middle East and North Africa (MENA) region, spanning the years 1990-2019, by age group, sex, underlying cause and sociodemographic index (SDI). METHODS: Publicly available data concerning the burden of vision loss were acquired from the Global Burden of Disease study 2019. The data encompassed all 21 countries within the MENA region for the period spanning 1990 to 2019. The estimates were reported as raw counts and age-standardised rates per 100,000, accompanied by their corresponding 95% uncertainty intervals (UIs). RESULTS: In 2019, MENA had an age-standardised point prevalence of 7040.0 (95% UI: 6195.0, 8002.7) and an YLD rate of 314.5 (222.1, 427.6) per 100,000 for vision loss, which were 11.1% (-12.5, -9.7) and 24.3% (-27.6, -20.8) lower, respectively, than in 1990. In 2019, Afghanistan [469.6 (333.0, 632.8)] had the largest age-standardised YLD rate and Turkey [210.7 (145.3, 290.9)] had the lowest. All countries showed a decrease in the age-standardised point prevalence and YLD rate between 1990 and 2019, except for Oman, Afghanistan, and Yemen. Furthermore, in 2019 the largest number of prevalent cases and YLDs were found in the 65-69 age group. Also in 2019, the age-standardised YLD rates in MENA exceeded the global averages for most age groups, for both males and females. In 2019, refractive disorders were the most common types of vision loss among children, adolescents, and middle-age adults in MENA, while near vision loss and cataracts were the most common among older adults. Finally, the burden of vision loss had a slightly negatively association with SDI over the period 1990-2019. CONCLUSION: Although the burden of vision loss has decreased over the last three decades, the prevalence remains high. These results underscore the importance of healthcare policymakers taking action to implement preventive measures, especially among the elderly and those living in low socioeconomic countries, to decrease the attributable burden in MENA.

Safety and efficacy of T-cell-redirecting bispecific antibodies for patients with multiple myeloma: a systematic review and meta-analysis.

BACKGROUND: In recent years, several bispecific antibodies (BsAbs) have been introduced that revolutionized the treatment approach for patients with multiple myeloma (MM). In the present study, we sought for conducting a systematic review and meta-analysis with the aim of evaluating the safety and efficacy of BsAbs in MM patients. METHODS: PubMed, Scopus, Web of Science, and Embase databases were systematically searched on June 10, 2022. Two steps of title/abstract and full-text screening were performed for selecting the relevant articles. The primary endpoint was considered to evaluate the safety of BsAbs by examining the rate of hematologic and non-hematologic adverse effects (AEs). The secondary outcome was set at the efficacy of BsAbs through pooling objective response rate (ORR), (stringent) complete response (sCR/CR), very good partial response (VGPR), and partial response (PR). RESULTS: Eleven publications with a total of nine evaluable BsAbs were included for qualitative and quantitative data synthesis. Hematologic AEs were more common among patients than non-hematologic events, with the most frequent events being anemia (41.4%), neutropenia (36.4%), and thrombocytopenia (26.3%). The most common non-hematological AE was infection, which occurred in 39.9% of patients, followed by dysgeusia (28.3%), fatigue (26.5%), and diarrhea (25.8%). Besides, 8.1% of patients experienced immune effector cell-associated neurotoxicity syndrome and neurotoxicity occurred in 5.1% of them. Moreover, 59.8% of patients experienced cytokine release syndrome. The pooled rate of deaths attributable to BsAbs was estimated at 0.1%. In terms of efficacy measures, the ORR was achieved in 62.6% of MM patients, and the pooled rates of sCR/CR, VGPR, and PR were 22.7%, 23.0%, and 12.1%, respectively. CONCLUSIONS: In an era with several emerging promising treatments for MM, BsAbs have achieved a high ORR and tolerable AEs in heavily pretreated patients. However, there is still room for developing BsAbs with a lower rate of AEs and capable of bypassing tumor evasion mechanisms.

The burden of major depressive disorder in the Middle East and North Africa region, 1990-2019.

BACKGROUND: Major depressive disorder (MDD) is one of the leading causes of disability. We aimed to report the MDD-attributable prevalence, incidence and years lived with disability (YLDs) in the Middle East and North Africa (MENA) region from 1990 to 2019 by age, sex and socio-demographic index (SDI). METHODS: Publicly available data on the burden of MDD were retrieved from the Global Burden of Disease (GBD) study 2019 for the 21 countries in MENA. The counts and age-standardised rates (per 100,000) were presented, along with their corresponding 95% uncertainty intervals. RESULTS: In 2019, MDD had an age-standardised point prevalence of 3322.1 and an incidence rate of 4921.7 per 100,000 population in MENA. Furthermore, there were 4.1 million YLDs in 2019. However, there were no substantial changes in the MDD burden over the period 1990-2019. In 2019, Palestine had the highest burden of MDD. The highest prevalence, incidence and YLDs attributable to MDD were found in the 35-39 age group. In 2019, the YLD rate in MENA was higher than the global rate for almost all age groups. Furthermore, there was a broadly negative association between the YLD rate and SDI. CONCLUSION: The study highlights the need to prevent the disorder using a multidisciplinary approach and for the provision of cost-effective treatments for those affected, in order to increase their quality of life.

Estimating mortality and disability in Peru before the COVID-19 pandemic: a systematic analysis from the Global Burden of the Disease Study 2019.

Background: Estimating and analyzing trends and patterns of health loss are essential to promote efficient resource allocation and improve Peru's healthcare system performance. Methods: Using estimates from the Global Burden of Disease (GBD), Injuries, and Risk Factors Study (2019), we assessed mortality and disability in Peru from 1990 to 2019. We report demographic and epidemiologic trends in terms of population, life expectancy at birth (LE), mortality, incidence, prevalence, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) caused by the major diseases and risk factors in Peru. Finally, we compared Peru with 16 countries in the Latin American (LA) region. Results: The Peruvian population reached 33.9 million inhabitants (49.9% women) in 2019. From 1990 to 2019, LE at birth increased from 69.2 (95% uncertainty interval 67.8-70.3) to 80.3 (77.2-83.2) years. This increase was driven by the decline in under-5 mortality (-80.7%) and mortality from infectious diseases in older age groups (+60 years old). The number of DALYs in 1990 was 9.2 million (8.5-10.1) and reached 7.5 million (6.1-9.0) in 2019. The proportion of DALYs due to non-communicable diseases (NCDs) increased from 38.2% in 1990 to 67.9% in 2019. The all-ages and age-standardized DALYs rates and YLLs rates decreased, but YLDs rates remained constant. In 2019, the leading causes of DALYs were neonatal disorders, lower respiratory infections (LRIs), ischemic heart disease, road injuries, and low back pain. The leading risk factors associated with DALYs in 2019 were undernutrition, high body mass index, high fasting plasma glucose, and air pollution. Before the COVID-19 pandemic, Peru experienced one of the highest LRIs-DALYs rates in the LA region. Conclusion: In the last three decades, Peru experienced significant improvements in LE and child survival and an increase in the burden of NCDs and associated disability. The Peruvian healthcare system must be redesigned to respond to this epidemiological transition. The new design should aim to reduce premature deaths and maintain healthy longevity, focusing on effective coverage and treatment of NCDs and reducing and managing the related disability.

Predictive value of PD-L1 expression in response to immune checkpoint inhibitors for gastric cancer treatment: a systematic review and meta-analysis.

BACKGROUND: Which patients may benefit more from immune checkpoint inhibitors (ICIs) is still an important question. The present study aimed to investigate the role of the PD-L1 molecule in predicting the effectiveness of PD-1/PD-L1 inhibitors in gastric cancer patients. METHOD: We searched PubMed, Scopus, Web of Science, and EMBASE databases as of 25 March 202225 March 2022. RESULTS: Ten articles were included. When we used the TPS method for PD-L1 expression, none of the patients in tumor proportion score (TPS)≥1% and TPS < 1% groups took advantage of ICI therapy in terms of OS and PFS. However, gastric cancer patients with combined-positive score (CPS)≥1, CPS ≥ 5, and CPS ≥ 10 tumors represented superior OS for ICIs over the control agents, while their counterparts (i.e. patients with CPS < 1, CPS < 5, and CPS < 10 tumors) did not. In the subgroup analysis when patients with CPS ≥ 1 were selected, Nivolumab improved the OS and PFS remarkably by 26% and 25% when compared with control agents, respectively. However, Pembrolizumab significantly increased the rate of disease progression by 47% relative to the control medications. CONCLUSION: Among patients suffering from gastric cancer, considering PD-L1 CPS thresholds seems to be a more reliable predictive factor than TPS threshold for lower rate of mortality when PD-1/PD-L1 inhibitors are administered.

The Burden of Attention-Deficit Hyperactivity Disorder (ADHD) in the Middle East and North Africa Region, 1990 to 2019.

OBJECTIVE: To report the burden of ADHD in the Middle East and North Africa (MENA) region from 1990 to 2019. METHODS: Publicly available data on the burden of ADHD were retrieved from the Global Burden of Disease study 2019. The counts and age-standardized rates (per 100,000) were presented. RESULTS: In 2019, ADHD had an age-standardized point prevalence of 1245.1 and a years lived with disability (YLD) rate of 15.1 per 100,000 in MENA, which were 7.2% (-11 to -3.3) and 7.2% (-11.2 to -2.7) lower, respectively, than in 1990. The highest YLD rate of ADHD was found in the 10 to 14 age group and there were no remarkable differences between males and females. No clear association was found between the YLD rate and the socio-demographic index. CONCLUSION: The burden of ADHD in the MENA region decreased over the period 1990 to 2019, and regularly updating the epidemiological information is suggested.

Emerging applications of phage therapy and fecal virome transplantation for treatment of Clostridioides difficile infection: challenges and perspectives.

Clostridioides difficile, which causes life-threatening diarrheal disease, is considered an urgent threat to healthcare setting worldwide. The current standards of care solely rely on conventional antibiotic treatment, however, there is a risk of promoting recurrent C. difficile infection (rCDI) because of the emergence of antibiotic-resistant strains. Globally, the alarming spread of antibiotic-resistant strains of C. difficile has resulted in a quest for alternative therapeutics. The use of fecal microbiota transplantation (FMT), which involves direct infusion of fecal suspension from a healthy donor into a diseased recipient, has been approved as a highly efficient therapeutic option for patients with rCDI. Bacteriophages or phages are a group of viruses that can infect and destroy bacterial hosts, and are recognized as the dominant viral component of the human gut microbiome. Accumulating data has demonstrated that phages play a vital role in microbial balance of the human gut microbiome. Recently, phage therapy and fecal virome transplantation (FVT) have been introduced as promising alternatives for the treatment of C. difficile -related infections, in particular drug-resistant CDI. Herein, we review the latest updates on C. difficile- specific phages, and phage-mediated treatments, and highlight the current and future prospects of phage therapy in the management of CDI.