Review of Asherman syndrome and its hysteroscopic treatment outcomes: experience in a low-resource setting.

BACKGROUND: Asherman syndrome is one of the endometrial factors that influence a woman's reproductive capacity. However, in our context, it needs to be well-documented. This study aimed to evaluate the clinical characteristics and hysteroscopic treatment outcomes of Asherman syndrome. METHOD: A retrospective follow-up study from January 1, 2019, to December 31, 2022, was conducted on cases of Asherman syndrome after hysteroscopic adhesiolysis at St.Paul's Hospital in Addis Ababa, Ethiopia. Clinical data were collected via telephone survey and checklist. Epidata-4.2 and SPSS-26 were employed for data entry and analysis, respectively. RESULT: A total of 177 study participants were included in the final analysis. The mean patient age was 31 years (range: 21-39) at the initial presentation, and 32.3 years (range: 22-40) during the phone interview. The majority of the patients (97.7%) had infertility, followed by menstrual abnormalities (73.5%). Among them, nearly half (47.5%) had severe, 38.4% had moderate, and 14.1% had mild Asherman syndrome. The review identified no factor for 51.4% of the participants. Endometrial tuberculosis affected 42 patients (23.7%). It was also the most frequent factor in both moderate and severe cases of Asherman syndrome. Only 14.7% of patients reported menstrual correction. Overall, 11% of women conceived. Nine patients miscarried, three delivered viable babies, and six were still pregnant. The overall rate of adhesion reformation was 36.2%. Four individuals had complications (3 uterine perforations and one fluid overload) making a complication rate of 2.3%. CONCLUSION: Our study revealed that severe forms of Asherman syndrome, which are marked by amenorrhea and infertility, were more common, leading to incredibly low rates of conception and the resumption of regular menstruation, as well as high recurrence rates. A high index of suspicion for Asherman syndrome, quick and sensitive diagnostic testing, and the development of a special algorithm to identify endometrial tuberculosis are therefore essential. Future multi-centered studies should focus on adhesion preventive techniques.

The role of Th-17 cells and IL-17 in the metastatic spread of breast cancer: As a means of prognosis and therapeutic target.

Metastatic breast cancer is one of the most common and well-known causes of death for women worldwide. The inflammatory tumor cell and other cancer hallmarks dictate the metastatic form and dissemination of breast cancer. Taking these into account, from various components of the tumor microenvironment, a pro-inflammatory infiltrative cell known as Th-17 plays an immense role in breast cancer proliferation, invasiveness, and metastasis. It has been demonstrated that IL-17, a pleiotropic pro-inflammatory cytokine generated by Th-17, is upregulated in a metastatic form of breast cancer. Recent research updates stated that chronic inflammation and mediators like cytokines and chemokines are causative hallmarks in many human cancers, including breast cancer. Therefore, IL-17 and its multiple downward signaling molecules are the centers of research attention to develop potent treatment options for cancer. They provide information on the role of IL-17-activated MAPK, which results in tumor cell proliferation and metastasis via NF-kB-mediated expression of MMP signaling. Overall, this review article emphasizes IL-17A and its intermediate signaling molecules, such as ERK1/2, NF-kB, MMPs, and VEGF, as potential molecular targets for the prevention and treatment of breast cancer.

Effect of Leptin on Chronic Inflammatory Disorders: Insights to Therapeutic Target to Prevent Further Cardiovascular Complication.

In response to obesity-associated chronic inflammatory disorders, adipose tissue releases a biologically active peptide known as leptin. Leptin activates the secretion of chemical mediators, which contribute to the pathogenesis of chronic inflammatory disorders, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and psoriasis. Conversely, adiposity and obesity are the major aggravating risk factors in the pathogenesis of metabolic syndrome (MetS), including type II diabetes mellitus and obesity-associated hypertension. Elevated level of leptin in obesity-associated hypertension causes an increase in the production of aldosterone, which also results in elevation of arterial blood pressure. Hyperleptinemia is associated with the progress of the atherosclerosis through secretion of pro-inflammatory cytokines, like interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), IL-17, and other cytokines to promote inflammation. The release of those cytokines leads to chronic inflammatory disorders and obesity-associated MetS. Thus, the aberrant leptin level in both MetS and chronic inflammatory disorders also leads to the complication of cardiovascular diseases (CVD). Therapeutic target of leptin regarding its pro-inflammatory effect and dysregulated sympathetic nervous system activity may prevent further cardiovascular complication. This review mainly assesses the mechanism of leptin on the pathogenesis and further cardiovascular risk complication of chronic inflammatory disorders.

Association of IL-10 (- 1082 A/G) and IL-6 (- 174 G/C) gene polymorphism with type 2 diabetes mellitus in Ethiopia population.

BACKGROUND: Interleukin (IL)-6 and IL-10 are the most important cytokine with pro and anti-inflammatory activities, respectively. Dysregulation of IL-6 and IL-10 are associated with increased risk of developing Type 2 Diabetes Mellitus (T2DM). Despite this, a fundamental understanding of both cytokine gene polymorphisms with its expression is critical in understanding of cellular mechanism of insulin resistance as well as T2DM intervention. Therefore, this study aimed to assess IL-6 (- 174 G/C) and IL-10 (- 1082 A/G) gene polymorphism, and its association with T2DM, North West Ethiopia. METHODS: A comparative cross-sectional study from January to May 2018 was conducted on study participants with T2DM and apparently healthy controls. Deoxyribonucleic acid (DNA) extraction and genotyping was carried out by using amplification refractory mutation system polymerase chain reaction to detect polymorphism of IL-6 and IL-10 gene at the position - 174 and - 1082, respectively. The logistic regression model was fitted to assess the association of between cytokine gene polymorphisms and T2DM. Odds ratio with 95% CI was determined to assess the presence and strength of association between the explanatory variables and outcome variable. A P-value < 0.05 was considered as statistically significant. RESULT: Participants carrying the GG genotype of IL-6 (- 174) (OR (95% CI) = 4.61 (2.07-10.54) was a high likelihood of having T2DM compared to those carrying the CC and AA genotypes. AA and AG genotypes of IL-10 (- 1082) were at lower odd of developing T2DM compared to those carrying the GG genotype. In addition, individuals carrying the G allele of IL-6 (- 174) have 2.82-fold odds of developing T2DM compared to individuals carrying the C allele (OR (95% CI) =2.81 (1.78-4.50)). CONCLUSION: Our study revealed that genetic polymorphisms of IL-6 (- 174) GG genotype is the potential host genetic risk factors to T2DM. While, IL-10 (- 1082) AA genotype is negatively associated with T2DM. Therefore, IL-6 (- 174) and IL-10 (- 1082) genetic variation may be considered as a biomarker for early screening and diagnosis of T2DM.

Hyperuricemia and Its Associated Factors Among Adult Staff Members of the Ethiopian Public Health Institute, Ethiopia.

BACKGROUND: Hyperuricemia is related not only to an increased risk of gouty arthritis but also to an increased risk of cardiovascular diseases, resistant hypertension, insulin resistance and progression of type 2 diabetes mellitus. However, to the best of our knowledge, the prevalence of hyperuricemia and its associated factors have rarely been assessed in Ethiopian populations. Therefore, this study aimed to determine the prevalence of hyperuricemia and its associated factors among adult staff members of the Ethiopian Public Health Institute. METHODS: An institution-based cross-sectional study was conducted from July 1 to October 28, 2018. A total of 402 study participants were selected using a simple random sampling technique. An interviewer-administered questionnaire was used to collect the data. A blood sample of approximately 5 mL was collected from each study participant after overnight fasting through standardized methods for biochemical tests, and analyses were carried out with an automated COBAS 6000 analyzer. Data analysis was performed by SPSS version 20 software. The factors associated with the outcome variable were identified by bivariable and multivariable logistic regression analyses, and a p value <0.05 was used to declare statistical significance. RESULTS: The mean age of the study participants was 37.13±10.5 (mean ± SD), and 51.5% of the participants were male. The overall prevalence of hyperuricemia (>5.7 mg/dL for females and >7 mg/dL for males) was found to be 31.0%. The multivariable logistic analysis revealed that age (AOR=1.59, 95% CI 1.01-2.78), sex (AOR=1.66, 95% CI 1.02-2.70), cigarette smoking (AOR=2.05, 95% CI 1.01-4.19) and serum low-density lipoprotein (LDL) (AOR=1.70, 95% CI 1.01-2.87) were significantly associated with hyperuricemia. CONCLUSION: The prevalence of hyperuricemia was relatively high compared to similar studies. Early screening for hyperuricemia in the general population, especially in those who are smokers, of older age and with high serum LDL levels, is vital to control its adverse effects at an early stage.

Knowledge and Practice Toward Prevention of SARS-CoV-2 Among Healthcare Workers at Delghi Primary Hospital During a Massive Test Campaign in Northwest Gondar, Ethiopia: Institution-Based Descriptive Cross-Sectional Survey.

BACKGROUND: Since December 29, 2019, severe acute respiratory syndrome coronavirus (SARS-CoV-2) has been spreading and is associated with notoriously increased morbidity and mortality of populations worldwide, including Ethiopia. Medicine and the healthcare system have been challenged by both first and second-waves of SARS-CoV-2. During this entire crisis, the main purpose of this study was to determine the current evidence on the level of awareness and prevention practice of healthcare workers (HCWs) at the district primary hospital, Delghi Primary Hospital (DPH) regarding COVID-19 in the overall effort to control the spread of the virus. METHODS: Institutional-based descriptive cross-sectional analysis was performed between late August and September 20, 2020. Participants of the study were HCWs with various occupations at DPH, North West Gondar, Ethiopia. In this study, among 112 health professions, we included a total of 104 HCWs. Written consent was obtained for willingness of the study participants from the DPH administrative office. Then, using a pre-tested, structured, and self-administered questionnaire, data were collected. The questionnaire included socio-demographics, sources of information, knowledge, and practice measures regarding COVID-19. The collected data were analyzed through IBM SPSS version 20. As a cut-off value, ≥8 out of 15 knowledge questions and ≥7 out of 14 practice questions were considered good knowledge and practice, respectively. RESULTS: The result of this study showed the majority of the respondents were male (71/104, (68.3%)), with a median age of 28 (minimum age 20 and maximum age 50) years. Thus, 94.2% (n=98/104) was the overall rate of correctly answered questions out of 15 knowledge questions. However, 40.6% of them had poor prevention practices. 73.1% of participants used regular hand-washing with soap and 64.4% used hand sanitizer and handshake avoidance equally for prevention purposes. Whereas, social distancing rule and mask-wearing were reported as impracticable by 55.8% and 44.2%, respectively. CONCLUSION: 94.2% of HCWs had a good level of knowledge about COVID-19; in contrast, lack of preventive practice was observed. This implies that there is a gap between knowledge and implementation of preventive measures toward the disease.

Omega-3 polyunsaturated fatty acids: anti-inflammatory and anti-hypertriglyceridemia mechanisms in cardiovascular disease.

Cardiovascular disease (CVD) is the world's most recognized and notorious cause of death. It is known that increased triglyceride-rich lipoproteins (TRLs) and remnants of triglyceride-rich lipoproteins (RLP) are the major risk factor for CVD. Furthermore, hypertriglyceridemia commonly leads to a reduction in HDL and an increase in atherogenic small dense low-density lipoprotein (sdLDL or LDL-III) levels. Thus, the evidence shows that Ω-3 fatty acids (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have a beneficial effect on CVD through reprogramming of TRL metabolism, reducing inflammatory mediators (cytokines and leukotrienes), and modulation of cell adhesion molecules. Therefore, the purpose of this review is to provide the molecular mechanism related to the beneficial effect of Ω-3 PUFA on the lowering of plasma TAG levels and other atherogenic lipoproteins. Taking this into account, this study also provides the TRL lowering and anti-inflammatory mechanism of Ω-3 PUFA metabolites such as RvE1 and RvD2 as a cardioprotective function.

Helminth Induced Immunoregulation and Novel Therapeutic Avenue of Allergy.

Allergic diseases are increasing at an alarming rate worldwide, particularly in developed countries. In contrast, there is a decrease in the prevalence of helminthic infections and other neglected diseases. The hygiene hypothesis elaborates parasitic infection, and allergy-associated diseases have an inverse relationship. Acute helminthic infection and allergic reaction stimulate Type 2 helper cells (Th2) immune response with up-regulation of cytokines IL-4-, IL-5-, and IL-13-mediated IgE and mast cell production, as well as eosinophilia. However, people who chronically suffer from helminthic infections are demarcated through polarized Th2 resulting in alternative macrophage activation and T regulatory response. This regulatory system reduces allergy incidence in individuals that are chronically diseased through helminth. As a result, the excretory-secretory (ES) substance derived from parasites and extracellular vesicular components can be used as a novel therapeutic modality of allergy. Therefore, the aim of this review meticulously explored the link between helminth infection and allergy, and utilization of the helminth secretome for therapeutic immunomodulation.

Inflammatory Cytokine: IL-17A Signaling Pathway in Patients Present with COVID-19 and Current Treatment Strategy.

Coronavirus disease 2019 (COVID-19) is a globally communicable public health disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Eradication of COVID-19 appears practically impossible but, therefore, more effective pharmacotherapy is needed. The deteriorated clinical presentation of patients with COVID-19 is mainly associated with hypercytokinemia due to notoriously elevated pro-inflammatory cytokines such as interleukin (IL)-1B, IL-6, IL-8, IL-17, granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), interferon-γ-inducible protein (IP10), monocyte chemoattractant protein (MCP1), and tumor necrosis factor-α (TNFα), and is usually responsible for cytokine release syndrome. In the cytokine storm, up-regulation of T-helper 17 cell cytokine IL-17A, and maybe also IL-17F, is mostly responsible for the immunopathology of COVID-19 and acute respiratory distress syndrome. Herein, I meticulously review the exuberant polarization mechanism of naïve CD4+ T cells toward Th17 cells in response to SARS-CoV-2 infection and its associated immunopathological sequelae. I also, propose, for clinical benefit, targeting IL-17A signaling and the synergic inflammatory cytokine IL-6 to manage COVID-19 patients, particularly those presenting with cytokine storm syndrome.

Role of Caspase-1 in the Pathogenesis of Inflammatory-Associated Chronic Noncommunicable Diseases.

Caspase-1 is the first and extensively studied inflammatory caspase that is activated through inflammasome assembly. Inflammasome is a cytosolic formation of multiprotein complex that aimed to start inflammatory response against infections or cellular damages. The process leads to an auto-activation of caspase-1 and consequent maturation of caspase-1 target molecules such as interleukin (IL)-1ß and IL-18. Recently, the role of caspase-1 and inflammasome in inflammatory-induced noncommunicable diseases (NCDs) like obesity, diabetes mellitus (DM), cardiovascular diseases (CVDs), cancers and chronic respiratory diseases have widely studied. However, their reports are distinct and even they have reported contrasting role of caspase-1 in the development and progression of NCDs. A few studies have reported that caspase-1/inflammasome assembley has a protective role in the initiation and progression of these diseases through the activation of the noncanonical caspase-1 target substrates like gasdermin-D and regulation of immune cells. Conversely, others have revealed that caspase-1 has a direct/indirect effect in the development and progression of several NCDs. Therefore, in this review, we systematically summarized the role of caspase-1 in the development and progression of NCDs, especially in obesity, DM, CVDs and cancers.

Inflammation Mediated Hepcidin-Ferroportin Pathway and Its Therapeutic Window in Breast Cancer.

Experimental and clinical data strongly support that iron is an essential element which plays a big role in cancer biology. Thus, hepcidin (Hp) and ferroportin (Fpn) are molecules that regulate and maintain the metabolism of iron. A peptide hormone hepcidin limits recycled and stored iron fluxes in macrophage and hepatic hepatocyte, respectively, to the blood stream by promoting degradation of the only iron exporter, Fpn, in the target cells. Moreover, the inflammatory microenvironment of breast cancer and altered hepcidin/ferroportin pathway is intimately linked. Breast cancer exhibits an iron seeking phenotype that is accomplished by tumor-associated macrophage (TAM). Because macrophages contribute to breast cancer growth and progression, this review will discuss TAM with an emphasis on describing how TAM (M2Ф phenotypic) interacts with their surrounding microenvironment and results in dysregulated Hp/Fpn and pathologic accumulation of iron as a hallmark of its malignant condition. Moreover, the underlying stroma or tumor microenvironment releases significant inflammatory cytokines like IL-6 and bone morphogenetic proteins like BMP-2 and 6 leading in aberrant Hp/Fpn pathways in breast cancer. Inflammation is primarily associated with the high intracellular iron levels, deregulated hepcidin/ferroportin pathway, and its upstream signaling in breast cancer. Subsequently, scholars have been reported that reducing iron level and manipulating the signaling molecules involved in iron metabolism can be used as a promising strategy of tumor chemotherapy. Here, we review the key molecular aspects of iron metabolism and its regulatory mechanisms of the hepcidin/ferroportin pathways and its current therapeutic strategies in breast cancer.

Role of Stem-Cell Transplantation in Leukemia Treatment.

Stem cells (SCs) play a major role in advanced fields of regenerative medicine and other research areas. They are involved in the regeneration of damaged tissue or cells, due to their self-renewal characteristics. Tissue or cells can be damaged through a variety of diseases, including hematologic and nonhematologic malignancies. In regard to this, stem-cell transplantation is a cellular therapeutic approach to restore those impaired cells, tissue, or organs. SCs have a therapeutic potential in the application of stem-cell transplantation. Research has been focused mainly on the application of hematopoietic SCs for transplantation. Cord blood cells and human leukocyte antigen-haploidentical donors are considered optional sources of hematopoietic stem-cell transplantation. On the other hand, pluripotent embryonic SCs and induced pluripotent SCs hold promise for advancement of stem-cell transplantation. In addition, nonhematopoietic mesenchymal SCs play their own significant role as a functional bone-marrow niche and in the management of graft-vs-host disease effects during the posttransplantation process. In this review, the role of different types of SCs is presented with regard to their application in SC transplantation. In addition to this, the therapeutic value of autologous and allogeneic hematopoietic stem-cell transplantation is assessed with respect to different types of leukemia. Highly advanced and progressive scientific research has focused on the application of stem-cell transplantation on specific leukemia types. We evaluated and compared the therapeutic potential of SC transplantation with various forms of leukemia. This review aimed to focus on the application of SCs in the treatment of leukemia.

Role of IFN and Complements System: Innate Immunity in SARS-CoV-2.

The critical role of the innate immune system has been confirmed in driving local and systemic inflammation and the cytokine release storm in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This dysregulated immune response is focused on interferon (IFN) and complement activation, which are crucial for the development of metabolic inflammation, local lung tissue damage, and systemic multi-organ failure. IFNs control viral infections by inducing expression of IFN-stimulated genes (ISGs) that restrict distinct steps of viral replication. Therefore, in this review article, we propose the mechanism of SARS-CoV-2-associated acute respiratory disease syndrome, and assess treatment options by considering IFNs and by targeting IFN-antagonist SARS-CoV-2 virulent gene products. Furthermore, we elaborate on the mechanism of the amplified complement-mediated inflammatory cytokine storm, and propose an antiviral and immunotherapeutic strategy against coronavirus disease 2019 (COVID-19).

Assessment of liver marker enzymes and its association with type 2 diabetes mellitus in Northwest Ethiopia.

OBJECTIVE: This study aimed to assess the level of aspartate aminotransaminase (AST), alanine aminotransaminase (ALT) and gamma-glutamyltransferase (GGT), and their association with type 2 diabetes mellitus in Northwest Ethiopia. RESULTS: Using a cross-sectional study, blood samples were collected from 192 Type 2 diabetes mellitus (T2DM) participants and 192 healthy age and sex-matched volunteers. The study was carried out from May to August 2017. The serum concentration of aspartate aminotransaminase, alanine aminotransaminase, and gamma-glutamyltransferase were measured using A25 Bio-system fully automatic chemistry analyzer and using the manufacturer's kit of the machine. Liver function test results of T2DM participant were significantly higher than those of the control group, serum ALT (46.06 ± 22. 38 IU/L) and serum AST (42.94 ± 19. 08 IU/L), P < 0.001, while the level of GGT in both study groups was not significantly associated (P = 0.065). In conclusion, the evaluation of liver marker enzymes showed a significant association with Type 2 diabetes participants compared with the controls.

Immunological Impacts of Diabetes on the Susceptibility of Mycobacterium tuberculosis.

The interaction between diabetes and major world infections like TB is a major public health concern because of rapidly rising levels of diabetes. The dual burden of tuberculosis (TB) and diabetes mellitus (DM) has become a major global public health problem. Diabetes mellitus is a major risk factor for the development of active and latent tuberculosis. Immune mechanisms contributing to the increased susceptibility of diabetic patients to TB are due to the defects in bacterial recognition, phagocytic activity, and cellular activation which results in impaired production of chemokines and cytokines. The initiation of adaptive immunity is delayed by impaired antigen-presenting cell (APC) recruitment and function in hyperglycemic host, which results in reduced frequencies of Th1, Th2, and Th17 cells and its secretion of cytokines having a great role in activation of macrophage and inflammatory response of tuberculosis. In addition, impaired immune response and killing of intracellular bacteria potentially increase bacterial load, chronic inflammation, and central necrosis that facilitate bacterial dissemination and miliary tuberculosis. Understanding of the immunological and biochemical basis of TB susceptibility in diabetic patients will tell us the rational development of implementation and therapeutic strategies to alleviate the dual burden of the diseases. Therefore, the aim of this review was focused on the association between diabetes and tuberculosis, focusing on epidemiology, pathogenesis, and immune dysfunction in diabetes mellitus, and its association with susceptibility, severity, and treatment outcome failure to tuberculosis.

Bacterial isolates and their antimicrobial susceptibility patterns among pediatric patients with urinary tract infections.

OBJECTIVE: Urinary tract infection is a common pediatric problem with the potential to produce long-term morbidity. Therefore, appropriate diagnosis and prompt treatment is required. However, studies about magnitude of uropathogenicity and antimicrobial resistance pattern of pediatric urinary tract infection (UTI) are lacking in resource limited countries including Ethiopia. This study was aimed to determine bacterial isolates, antimicrobial susceptibility pattern among pediatric patients with UTI. MATERIAL AND METHODS: A cross- sectional study was conducted. Pathogenic bacterial isolates were identified by culture and biochemical methods following standard procedures. Antimicrobial susceptibility testing of the isolates for commonly used antibiotics was done using the standard disc diffusion method on Muller Hinton agar. Associations between dependent and independent variables were measured using chi-square test and within 95% confidence interval. P values <0.05 were considered as statistically significant. RESULTS: A total of 310 pediatric patients were included in the study, and 82 (26.45%) bacterial isolates were detected. Gram- negative bacteria were predominant etiologic agents of UTI in this study. E. coli was the most frequently occurring pathogen (n=45; 54.88%) followed by S. aureus and P.aeruginosa (n=8; 9.75% for both), P. vulgaris, P.aeruginosa (n=4; 4.88%, for both) and Enterococcus species (n=3; 3.66%). All K. pneumoniae, P. mirabilis, and K. ozanae straines were 100% resistance to ampicillin, followed by P. aeruginosa (87.5%) and E. coli (69%). While all Gram- positive bacterial isolates were 100% sensitive to ciprofloxacin. Malnutrition, history of catherization and previous history of UTI were independently associated with UTI (p=0.000). CONCLUSION: There was a high prevalence of uropathogenic bacteria and drug resistance particularly to ampicillin (72%) and tetracycline (37.80%). This condition indicates that antibiotic selection should be based on knowledge of the local prevalence of bacterial organisms and antibiotic sensitivities rather than empirical treatment.