Intensive pre-operative information course (IPIC) and pre-operative weight loss results in long-term sustained weight loss following bariatric surgery: 11 years results from a tertiary referral centre.

INTRODUCTION: Outcomes of long-term (5-10-year) weight loss have not been investigated thoroughly and the role of pre-operative weight loss on long-term weight loss, among other factors, are unknown. Our regional bariatric service introduced a 12 week intensive pre-operative information course (IPIC) to optimise pre-operative weight loss and provide education prior to bariatric surgery. The present study determines the effect of pre-operative weight loss and an intense pre-operative information course (IPIC), on long-term weight outcomes and sustained weight loss post-bariatric surgery. METHODS: Data were collected prospectively from a bariatric center (2008-2022). Excess weight loss (EWL) ≥ 50% and ≥ 70% were considered outcome measures. Survival analysis and logistic regression identified variables associated with overall and sustained EWL ≥ 50% and ≥ 70%. RESULTS: Three hundred thirty-nine patients (median age, 49 years; median follow-up, 7 years [0.5-11 years]; median EWL%, 49.6%.) were evaluated, including 158 gastric sleeve and 161 gastric bypass. During follow-up 273 patients (80.5%) and 196 patients (53.1%) achieved EWL ≥ 50% and ≥ 70%, respectively. In multivariate survival analyses, pre-operative weight loss through IPIC, both < 10.5% and > 10.5% EWL, were positively associated with EWL ≥ 50% (HR 2.23, p < 0.001) and EWL ≥ 70% (HR 3.24, p < 0.001), respectively. After a median of 6.5 years after achieving EWL50% or EWL70%, 56.8% (154/271) had sustained EWL50% and 50.6% (85/168) sustained EWL70%. Higher pre-operative weight loss through IPIC increased the likelihood of sustained EWL ≥ 50% (OR, 2.36; p = 0.013) and EWL ≥ 70% (OR, 2.03; p = 0.011) at the end of follow-up. CONCLUSIONS: IPIC and higher pre-operative weight loss improve weight loss post-bariatric surgery and reduce the likelihood of weight regain during long-term follow-up.

OMICRON (B.1.1.529): A new SARS-CoV-2 variant of concern mounting worldwide fear.

Recent emergence of the SARS-CoV-2 variant as OMICRON has become a global concern. This short note highlights the identification and global spread of OMICRON which has spread over 77 nations by now, which resulted in many hypotheses about its origin and degree of infectivity. The detection of mutations in the RBD region of Spike protein is a concern by surpassing vaccine immunity. The ahead will speak about its transmission potentiality, infectivity, disease morbidity as well as its effect on COVID-19 vaccines.

Placenta as a site of HEV replication and inflammatory cytokines modulating the immunopathogenesis of HEV in pregnant women.

Viral hepatitis E is an under-estimated clinical entity with high mortality (20%-30%), especially in the third trimester of pregnancy. As complications due to hepatitis E virus (HEV) in pregnancy is much greater, it is hypothesized that HEV may cross the placenta and replicate in placental tissues even weeks after clearance from the blood, and cytokines may play a role in the immunopathogenesis of HEV in pregnancy. A total of 12 pregnant women with features of acute viral hepatitis/acute liver failure and positive for either HEV-immunoglobulin M (IgM)/HEV-RNA and 30 pregnant women negative for HEV RNA/IgM/immunoglobulin G were enrolled as study subjects and healthy controls, respectively. Following delivery, 5 ml blood was collected from the mother for HEV-RNA. Replicative RNA and viral load in placental tissue were detected through Real-Time PCR. Placental tissues from the maternal/fetal sides were stained for HEV antigen using HEV-open reading frame-2 antibody by immunohistochemistry (IHC) and for histopathological changes by haematoxylin and eosin. Plasma samples were tested for interleukin (IL)-1ß and IL-18 cytokine levels using Duo-R&D ELISA kit, whereas peripheral blood mononuclear cells were used to study the inflammasomes and IL-1ß and IL-18 cytokine genes expression.Of the 10 HEV RNA-positive sera, 9 had HEV RNA either in the maternal/fetal side of the placenta with the mean viral load of 137.4 IU/ml. Of the 10 HEV RNA-positive pregnant women, stillbirth in two and fetal and maternal death in one case was reported. IHC revealed strong brownish cytoplasmic staining (HEV antigen) in cytotrophoblasts and syncytiotrophoblast cells in positive samples. The maternal/fetal side of the infected placenta showed irregular intervillous fibrin deposition as well as tissue necrosis. The mean levels of IL-1ß and IL-18 cytokines in serum of infected subjects were significantly higher than the healthy controls (17.31 ± 4.462 vs. 8.85 ± 4.36 pg/ml; p < 0.0001*** and 2275 ± 536.9 vs. 1085 ± 531.7 pg/ml; p < 0.0001***), respectively. Detecting replicative HEV RNA and HEV antigen in placental tissues indicated the extra-hepatic replication of HEV. Furthermore, placental tissue necrosis and significant rise of cytokine levels in HEV-infected pregnant women might be contributing to the HEV pathogenesis in pregnancy.

Waves and variants of SARS-CoV-2: understanding the causes and effect of the COVID-19 catastrophe.

The coronavirus disease-19 has left a permanent mark on the history of the human race. Severe acute respiratory syndrome coronavirus-2 is a positive-sense single-stranded RNA virus, first reported in Wuhan, China, in December 2019 and from there took over the world. Being highly susceptible to mutations, the virus's numerous variants started to appear, and some were more lethal and infectious than the parent. The effectiveness of the vaccine is also affected severely against the new variant. In this study, the infectious mechanism of the coronavirus is explained with a focus on different variants and their respective mutations, which play a critical role in the increased transmissibility, infectivity, and immune escape of the virus. As India has already faced the second wave of the pandemic, the future outlook on the likeliness of a third wave with respect to the Indian variants such as kappa, delta, and Delta Plus is also discussed. This review article aims to reflect the catastrophe of the variants of SARS-CoV-2 and the possibility of developing even more severe variants in the near future.

Neurological toll of COVID-19.

The first case of coronavirus illness was discovered in Wuhan, China, in January 2020 and quickly spread worldwide within the next couple of months. The condition was initially only linked with respiratory disorders. After the evolution of various variants of the SARS-CoV-2, the critical impact of the virus spread to multiple organs and soon, neurological disorder manifestations started to appear in the infected patients. The review is focused on the manifestation of various neurological disorders linked with both the central nervous system and peripheral nervous system. Disorders such as cytokine release syndrome, encephalitis, acute stroke, and Bell's palsy are given specific attention and psychological manifestations are also investigated. For a clear conclusion, cognitive impairment, drug addiction disorders, mood and anxiety disorders, and post-traumatic stress disorder are all fully examined. The association of the SARS-CoV-2 with neurological disorders and pathway is yet to be clear. For better understanding, the explanation of the possible mechanism of viral infection influencing the nervous system is also attempted in the review. While several vaccines and drugs are already involved in treating the SARS-CoV-2 condition, the disease is still considered fatal and more likely to leave permanent neurological damage, which leads to an essential requirement for more research to explore the neurological toll of the COVID-19 disease.

NLRP3 Inflammasome Activation is a Prognostic Marker of Recovery in HEV-Infected Patients.

Hepatitis E contributes to 3.3 million acute hepatitis cases worldwide with 30% mortality in pregnant women. Pathogenesis of Hepatitis E is complex; thus, the present study was aimed at inflammasomes and associated cytokines in the immunopathogenesis of viral hepatitis E. PBMCs were isolated from 45 HEV IgM/HEV RNA-positive AVH/ALF and 19 healthy individuals and processed for mRNA expressions of NLRs, RLRs, and cytokines. PBMCs were cultured and stimulated with HEV-pORF-2 peptide in vitro for mRNA expression by RT-PCR and cytokines levels in serum/culture supernatant by ELISA. siRNA transfection and post-silencing effect in AVH PBMCs were also assessed by NLRP3 gene expression and IL-1ß and IL-18 levels by ELISA. The results demonstrated high viral load in ALF than AVH cases. mRNA expression of NLRP3 in AVH patients was found to be positively correlated with IL-18 (r = 0.74) and IL-1ß (r = 0.68); P < 0.0001***. Significant levels of serum IL-1ß and IL-18 cytokines were observed in AVH as compared to ALF patients. The levels of IL-1ß in the culture supernatant in mock and stimulated conditions were significantly higher in AVH than in ALF patients. Significant downregulation in NLRP3 gene expression was correlated with the reduced levels of IL-1ß and IL-18 cytokines in NLRP3-siRNA-transfected PBMCs. This study highlighted the significance of upregulated NLRP3 inflammasome leading to increased production of IL-18 and IL-1ß cytokines in sera of AVH patients. Thus, it indicated the role of Th1 response acting through the NLRP3 pathway which might have been helpful in the recovery of AVH patients. These promising results open multiple treatment avenues where specific inhibitors can be designed to modulate the progress of disease and its pathogenicity.

Endophytic Microbial Diversity: A New Hope for the Production of Novel Anti-tumor and Anti-HIV Agents as Future Therapeutics.

Cancer is a collective name for a variety of diseases that can begin in virtually every organ or body tissue as abnormal cells develop uncontrollably and ten million new cancer cases are diagnosed all over the world at present. Whereas HIV is a virus that makes people susceptible to infection and contributes to the condition of acquired immune deficiency syndrome (AIDS). Almost 37 million people are currently diagnosed with HIV and 1 million people die every year, which is the worst-case scenario. Potential medicinal compounds have played a crucial role in the production of certain clinically beneficial novel anti-cancer and anti-HIV agents that are produced from natural sources especially from plants. These include Taxol, Vinblastine, Podophyllotoxin, Betulinic acid, Camptothecin, and Vincristine, etc. In the past decades, bioactive compounds were extracted directly from the plant sources which was more time consuming, led to low yield productivity, high cost, and bad impact on biodiversity. Endophytes, the microorganisms that reside inside the host plant by not causing any kind of harm to them and have potential applications in agriculture, medicine, pollution, and food industries. Therefore, by isolating and characterizing novel endophytes from medicinal plants and extracting their secondary metabolites to produce useful bioactive compounds can be beneficial for well-being and society as a future therapeutics. This approach is not harmful to biodiversity economical, timesaving, low cost, and can lead to the discovery of various industrial and commercially important novel anti-tumor and anti-HIV agents in the future. The Himalayas are home to several medicinal plants and the endophytic microbial biodiversity of the Himalayan region is also not much explored yet. However, the effect of compounds from these endophytes on anticancer and antiviral activity, especially anti-HIV has been largely unexplored. Hence, the present review is designed to the exploration of endophytic microbial diversity that can give rise to the discovery of various novel potential industrially valuable bioactive compounds that can lessen the rate of such type of pandemic diseases in the future by providing low-cost future therapeutics in future.

Changes in Stress-Mediated Markers in a Human Cardiomyocyte Cell Line under Hyperglycemia.

Diabetes is a major risk factor for cardiovascular diseases, especially cardiomyopathy, a condition in which the smooth muscles of the heart become thick and rigid, affecting the functioning of cardiomyocytes, the contractile cells of the heart. Uncontrolled elevated glucose levels over time can result in oxidative stress, which could lead to inflammation and altered epigenetic mechanisms. In the current study, we investigated whether hyperglycemia can modify cardiac function by directly affecting these changes in cardiomyocytes. To evaluate the adverse effect of high glucose, we measured the levels of gap junction protein, connexin 43, which is responsible for modulating cardiac electric activities and Troponin I, a part of the troponin complex in the heart muscles, commonly used as cardiac markers of ischemic heart disease. AC16 human cardiomyocyte cells were used in this study. Under hyperglycemic conditions, these cells demonstrated altered levels of connexin 43 and Troponin-I after 24 h of exposure. We also examined hyperglycemia induced changes in epigenetic markers: H3K9me1, Sirtuin-1 (SIRT1), and histone deacetylase (HDAC)-2 as well as in inflammatory and stress-related mediators, such as heat shock protein (HSP)-60, receptor for advanced glycation end products (RAGE), toll-like receptor (TLR)-4, high mobility group box (HMGB)-1 and CXC chemokine receptor (CXCR)-4. Cardiomyocytes exposed to 25mM glucose resulted in the downregulation of HSP60 and SIRT1 after 48 h. We further examined that hyperglycemia mediated the decrease in the gap junction protein CX43, as well as CXC chemokine receptor CXCR4 which may affect the physiological functions of the cardiomyocytes when exposed to high glucose for 24 and 48 h. Upregulated expression of DNA-binding nuclear protein HMGB1, along with changes in histone methylation marker H3K9me1 have demonstrated hyperglycemia-induced damage to cardiomyocyte at 24 h of exposure. Our study established that 24 to 48 h of hyperglycemic exposure could stimulate stress-mediated inflammatory mediators in cardiomyocytes in vitro. These stress-related changes in hyperglycemia-induced cardiomyocytes may further initiate an increase in injury markers which eventually could alter the epigenetic processes. Therefore, epigenetic and inflammatory mechanisms in conjunction with alterations in a downstream signaling pathway could have a direct effect on the functionality of the cardiomyocytes exposed to high glucose during short and long-term exposures.

High-Mobility Group Box 1 Protein Signaling in Painful Diabetic Neuropathy.

Diabetes is a global epidemic and more than 50% diabetic patients are also diagnosed with neuropathy, which greatly affects the quality of life of the patients. Available treatments are not always successful due to the limited efficacy and complications, such as addiction and dependency. Studies have implicated that high mobility group box1 (HMGB1) protein plays a crucial role in neuroinflammation and the development of neuropathic conditions. HMGB1 is a proinflammatory cytokine that can be released from necrotic cells in passive form or in response to inflammatory signals as an active form. HMGB1 is the ligand for the receptor for advanced glycation end products (RAGE), and toll-like receptors, (TLR)-2 and TLR4, which also indirectly activates C-X-C chemokine receptor type 4 (CXCR4). We investigated whether blocking of HMGB1 can reduce pain and inflammation in diabetic neuropathic animals to further understand the role of HMGB1 in diabetic neuropathy. Type 2 diabetic rats and mice were treated with natural inhibitor of HMGB1, glycyrrhizin (GLC) for five days/week for four weeks at a dose of 50 mg/kg per day by intraperitoneal injection. The animals were divided into three categories: naïve control, diabetic alone, diabetic with GLC treatment. All of the behavioral analyses were conducted before and after the treatment. The expression of inflammatory markers and changes in histone acetylation in the peripheral nervous system were measured by immunohistochemistry and Western blot analysis after the completion of the treatment. Our study revealed that TLR4, HMGB1, CXCR4, and Nod-like receptor protein 3 (NLRP3) levels were increased in the spinal and dorsal root ganglia (DRG) neurons of Type 2 diabetic mice and rats with painful neuropathy. GLC treatment inhibited the increases in TLR4, NLRP3, and CXCR4 expressions and improved the mechanical and thermal pain threshold in these animals. Immunohistochemical studies revealed that hyperglycemia mediated inflammation influenced HMGB1 acetylation and its release from the neurons. It also altered histone 3 acetylation in the microglial cells. The inhibition of HMGB1 by GLC prevented the release of HMGB1 as well as H3K9 acetylation. These findings indicate that the interruption of HMGB1 mediated inflammation could ameliorate diabetic neuropathy and might exhibit a unique target for the treatment.

Solvent-Tolerant Acyltransferase from Bacillus sp. APB-6: Purification and Characterization.

Amidase from Bacillus sp. APB-6 with very good acyltransferase activity was purified to homogeneity with a purification fold of 3.68 and 53.20% enzyme yield. The purified protein's subunit molecular mass was determined approximately 42 kDa. Hyperactivity of the enzyme was observed at pH 7.5 (150 mM, potassium-phosphate buffer) and 50 °C of incubation. An enhancement in activity up to 42% was recorded with ethylenediaminetetraacetic acid and dithiothreitol. The kinetic parameter K m values for substrates: acetamide and hydroxylamine-hydrochloride were 73.0 and 153 mM, respectively. Further, the V max for acyltransferase activity was 1667 U/mg of protein and the K i for acetamide was calculated as 37.0 mM. The enzyme showed tolerance to various organic solvents (10%, v/v) and worked well in the biphasic reaction medium. The acyltransferase activity in presence of solvents i.e. biphasic medium may prove highly favorable for the transformation of hydrophobic amides, which otherwise is not possible in simple aqueous phase.

Viral vector mediated continuous expression of interleukin-10 in DRG alleviates pain in type 1 diabetic animals.

Painful diabetic neuropathy is a common and difficult to treat complication of diabetes. A growing body of evidence implicates the role of inflammatory mediators in the damage to the peripheral axons and in the pathogenesis of neuropathic pain. Increased expression of pro-inflammatory cytokines such as interleukin (IL)-1ß and tumor necrosis factor (TNF)-α in the peripheral nervous system suggests the possibility of change in pain perception in diabetes. In this study we investigated that continuous delivery of IL10 in the nerve fibers achieved by HSV vector mediated transduction of dorsal root ganglion (DRG) in animals with Type 1 diabetes, blocks the nociceptive and stress responses in the DRG neurons by reducing IL1ß expression along with inhibition of phosphorylation of p38 MAPK (mitogen-activated protein kinase) and protein kinase C (PKC). The continuous expression of IL10 also alters Toll like receptor (TLR)-4 expression in the DRG with increased expression of heat shock protein (HSP)-70 in conjunction with the reduction of pain. Taken together, this study suggests that macrophage activation in the peripheral nervous system may be involved in the pathogenesis of pain in Type 1 diabetes and therapeutic benefits of HSV mediated local expression of IL10 in the DRG with the reduction of a number of proinflammatory cytokines, subsequently inhibits the development of painful neuropathy along with a decrease in stress associated markers in the DRG. This basic and preclinical study provides an important evidence for a novel treatment strategy that could lead to a clinical trial for what is currently a treatment resistant complication of diabetes.

Role of Histone Deacetylase Inhibitor in Diabetic Painful Neuropathy.

Diabetic painful neuropathy (DPN) is one of the most detrimental complications of diabetes. Alterations in neuroinflammatory mediators play significant roles in the development of DPN. Infiltration of the neutrophils and monocyte/macrophages contributes substantial role in the degenerative process of the distal sciatic nerve by forming neutrophil extracellular traps (NETs) under diabetic condition. Citrullination of histones due to increase in protein arginine deiminase (PAD) enzyme activity under hyperglycemia may promote NET formation, which can further increase the cytokine production by activating macrophages and proliferation of neutrophils. This study reveals that the increase in histone deacetylases (HDAC) is crucial in DPN and inhibition of HDAC using HDAC inhibitor (HDACi) FK228 would suppress NETosis and alleviate diabetic nerve degeneration and pain. FK228, also known as romidepsin, is FDA approved for the treatment of cutaneous T-cell lymphoma yet the molecular mechanisms of this drug are not completely understood in DPN. In this study, type 2 diabetic (T2D) mice with pain were treated with HDACi, FK228 1 mg/kg; I.P. 2 × /week for 3 weeks. The results demonstrate that FK228 treatment can alleviate thermal hyperalgesia and mechanical allodynia significantly along with changes in the expression of HDACs in the dorsal root ganglia (DRG) and spinal cord dorsal horn neurons of diabetic animals. The results also indicate that FK228 treatment can alter the expression of neutrophil elastase (NE), extracellular or cell free DNA (cfDNA), citrullinated histone-3 (CitH3), PADI4, growth-associated protein (GAP)-43, and glucose transporter (GLUT)-4. Overall, this study suggests that FK228 could amend the expression of nerve regeneration markers and inflammatory mediators in diabetic animals and may offer an alternative treatment approach for DPN.

EXPRESS: Effectiveness of HMG-CoA reductase inhibitors on inflammation and metabolic markers in the US-Mexico border Hispanic population.

HMG-CoA reductase inhibitors (statins) are commonly used for dyslipidemia management to reduce the risk of cardiovascular disease (CVD). High-sensitivity C-reactive protein (hs-CRP) is an emerging systematic low-grade inflammatory marker associated with atherosclerotic CVD development. Despite racial/ethnic disparities in the use and response of statins and the anti-inflammatory effects of statins, the effectiveness of statins on inflammation and metabolic markers is unknown among Hispanics. We performed a retrospective cohort study using 150 adult patients scheduled for an annual physical exam at a family medicine clinic between January 1, 2021, and December 31, 2021. Effect size with a 95% confidence interval (CI) was estimated using adjusted regression analyses. Among 150 patients, 52 (34.67%) received statins. Patients who received statins had significantly reduced median hs-CRP (1.9 vs. 3.2, p=0.007), mean low-density lipoprotein (LDL-C) (101.18 vs. 124.6, p<0.001), and total cholesterol (172.6 vs. 194.5, p<0.001) concentrations compared to those who did not receive statins. In the propensity-scores matched analysis, lower concentrations of log-transformed hs-CRP (regression coefficient [RC], -0.48; 95%CI: -0.89, -0.07), LDL-C (RC, -19.57; 95%CI: -33.04, -6.1), and total cholesterol (RC, -23.47; 95%CI: -38.96, -7.98) were associated with statin use. In addition, hepatic steatosis (adjusted relative risk [aRR]=0.25; 95%CI: 0.08, 0.78, p= 0.017) was significantly lower among patients with the use of statins. Our study suggests that HMG-CoA reductase inhibitors may help reduce inflammation among Hispanic patients with dyslipidemia and hypertension. These findings have useful implications for preventing risk and disparities associated with cardiovascular and other inflammatory-induced diseases among the fastest-growing US Hispanic minorities.

Inhibiting Fatty Acid Amide Hydrolase Ameliorates Enteropathy in Diabetic Mice: A Cannabinoid 1 Receptor Mediated Mechanism.

Gastrointestinal (GI) dysmotility in diabetics exhibits fecal incontinence or constipation which affects patients' quality of life. In this study, we aimed to understand the pattern of GI transit in type 1 diabetic (T1D) mice and whether inhibiting endocannabinoid degradation would exhibit therapeutic effect. Whole gut-transit time and fecal-pellet output were measured at 16 week post-diabetes. T1D mice treated with fatty acid amide hydrolase (FAAH) inhibitor URB597 showed reduced fecal output as well as improved gut transit time. Cannabinoid 1 receptor antagonist, AM251 blocked the effects of URB597, which may demonstrate that FAAH inhibitor is a potential remedial strategy for GI dysmotility.

3D Biofabrication of a Cardiac Tissue Construct for Sustained Longevity and Function.

In this study, we developed three-dimensional (3D) printed annular ring-like scaffolds of hydrogel (gelatin-alginate) constructs encapsulated with a mixture of human cardiac AC16 cardiomyocytes (CMs), fibroblasts (CFs), and microvascular endothelial cells (ECs) as cardiac organoid models in preparation for investigating the role of microgravity in cardiovascular disease initiation and development. We studied the mechanical properties of the acellular scaffolds and confirmed their cell compatibility as well as heterocellular coupling for cardiac tissue engineering. Rheological analysis performed on the acellular scaffolds showed the scaffolds to be elastogenic with elastic modulus within the range of a native in vivo heart tissue. The microstructural and physicochemical properties of the scaffolds analyzed through scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy-attenuated total reflectance (ATR-FTIR) confirmed the mechanical and functional stability of the scaffolds for long-term use in in vitro cell culture studies. HL-1 cardiomyocytes bioprinted in these hydrogel scaffolds exhibited contractile functions over a sustained period of culture. Cell mixtures containing CMs, CFs, and ECs encapsulated within the 3D printed hydrogel scaffolds exhibited a significant increase in viability and proliferation over 21 days, as shown by flow cytometry analysis. Moreover, via the expression of specific cardiac biomarkers, cardiac-specific cell functionality was confirmed. Our study depicted the heterocellular cardiac cell interactions, which is extremely important for the maintenance of normal physiology of the cardiac wall in vivo and significantly increased over a period of 21 days in in vitro. This 3D bioprinted "cardiac organoid" model can be adopted to simulate cardiac environments in which cellular crosstalk in diseased pathologies like cardiac atrophy can be studied in vitro and can further be used for drug cytotoxicity screening or underlying disease mechanisms.

Avian influenza revisited: concerns and constraints.

Avian influenza (AVI) is being known for its pandemic potential and devastating effects on poultry and birds. The AVI outbreaks in domesticated birds are of concern because the Low pathogenic avian influenza virus (LPAI) tends to evolve into a High pathogenic avian influenza virus (HPAI) resulting in the rapid spread and significant outbreak in poultries. The containment should be rapid and stringent precautions should be taken in handling the infected poultry cases or infected materials. In general, AVI viruses do not replicate efficiently in humans, indicating that transmitting these viruses to humans directly is a very rare preference. However, the HPAI ability to the cross-species barrier and infect humans has been known for H5N1 and H7N9. Recently, the world's first human case of transmission of the H5N8 strain from the avian species to humans has been documented. In this recent scenario, it is worth discussing the strain variations, disease severity, economic loss, and effective controlling strategies for controlling avian influenza.