Enterocytozoon hepatopenaei (EHP) is highly contagious and has been detected in almost all major shrimp farms in our country. The main symptom of EHP infection is the retarded growth of shrimp and it causes huge economic losses to the aquaculture industry. However, the mechanism of growth retardation remains unclear, so we explored the physiological response mechanisms under EHP experimental infection, including the metabolic processes and oxidative stress. The results showed that EHP infection changed the substance metabolism and growth process. In addition, EHP induced oxidative stress and led to the accumulation of lipid peroxidation products, which may also be an important cause of hepatopancreas tissue damage. It has been observed that severe EHP infection may lead to white feces. This study provides new insights into the subsequent physiological study of host infection with EHP and contributes to the disease prevention and treatment of EHP.Enterocytozoon hepatopenaei (EHP) is highly contagious and can cause hepatopancreatic microsporidiosis (HPM), which is typically characterized by the slow growth of shrimp. In this study, the differences in histology, metabolism, oxidative stress and growth between healthy and EHP-infected Penaeus vannamei were analyzed using an EHP challenge experiment. Histology showed that EHP caused lesions in the hepatic tubules of P. vannamei, such as hepatic tubular atrophy and epithelial cell shedding, with mature spores. Meanwhile, white feces may appear when the infection is severe. Furthermore, the content of total protein, glycogen, ATP and glucose in the EHP challenge group was significantly reduced. The qPCR results showed that EHP infection changed the expression of key genes in glucose metabolism, among which hexokinase (HK), phosphofructokinase (PFK), pyruvatekinase (PK), citrate synthase (CS) and isocitric dehydrogenase (IDH) were significantly down-regulated, while phosphoenolpyruvate carboxykinase (PEPCK), fructose bisphosphatase (FBP) and glucose-6-phosphatase (G6P) were significantly up-regulated. Obviously, the expression of growth-related genes was disordered. Simultaneously, the antioxidant genes manganese superoxide dismutase (MnSOD), catalase (CAT), glutathione peroxidase (GPX), glutathione-S-transferases (GST) and nuclear factor E2-related factor2 (Nrf2) were up-regulated to varying degrees in the EHP challenge group, and EHP infection induced significant increases in the oxidative damage products lipid peroxide (LPO) and malondialdehyde (MDA). Ultimately, the shrimp weight of the challenge group was 6.85 ± 0.86 g, which was significantly lower than that of the control group (8.95 ± 0.75 g). Taken together, we speculate that EHP changes the substance metabolism and growth process by causing oxidative damage to the hepatopancreas, which may lead to the growth retardation of P. vannamei. Penaeus vannamei  is the major shrimp culture species in the world, accounting for the highest proportion of crustacean culture production, and has important economic value P. vannamfor WSSV  using PC2 and 10 mmol/L HEPES, pH 7.45, 780 mOsm/kg) at a ratio of 1:1 (hemolymph:anticoagulant), which was located in the abdominal sinus of the shrimp [g for 10 min was performed and the supernatant was collected for subsequent experiments.The sampled tissues were hepatopancreas, muscle and hemolymph. The hepatopancreas and muscle samples were immediately frozen in liquid nitrogen and stored in an ultra-low-temperature refrigerator (−80 °C). The hemolymph was collected with a 1 mL sterile syringe containing anticoagulant  and EHP185 (R: 5′-CCAGCATTGTCGGCATAG-3′) [2O at a total volume of 20 μL. A total of 40 cycles of the qPCR reaction program were set at 95 °C for 30 s, 95 °C for 10 s and 60 °C for 45 s. A 96-well plate was used for the experiment, and each sample was subjected to three technical and three biological replicates. Gradient dilution was performed according to the constructed plasmid concentration, and a standard curve was established to calculate the EHP load.The total DNA of the shrimp hepatopancreas was extracted using a marine animal tissue genomic DNA extraction kit . EHP-specific primers were used for PCR amplification to identify whether the shrimp were infected with EHP, and the primer sequences were EHP-358F (5′-ATTAGACACCGCTGTAGTTC-3′) and EHP-358R (5′-GTTATTGCCTTCTCCCTC-3′) [The hepatopancreas at different sampling times was fixed using Davidson fixative . After tThe white feces were stained using calcofluor white (CFW) dye . First, the feces were collected in a 1.5 mL EP tube, homogenized using a grinding rod and centrifuged, and a drop was placed on a glass slide. After removing the excess water, the CFW working solution was added and mixed for dyeing at room temperature, and then the size of spores was observed and calculated using a fluorescence microscope  (Image J 2. software) .Trizol  was used to extract the total hepatopancreas. After chloroform extraction, isopropanol precipitation, multiple centrifugation and other steps, the RNA was collected in an enzyme-free EP tube and stored at −80 °C. The RNA quality was evaluated using DeNovix DS-11  and 1% agarose gel electrophoresis. The cDNA was synthesized using a Fast King RT Kit , according to the commercial instructions and stored at −20 °C for the experiments.HK), phosphofructokinase (PFK) and pyruvatekinase (PK), of the glycolyic pathway; two key genes, citrate synthase (CS) and isocitric dehydrogenase (IDH), of the tricarboxylic acid cycle (TCA) and three key enzymes, phosphoenolpyruvate carboxykinase (PEPCK), fructose bisphosphatase (FBP) and glucose-6-phosphatase (G6P), of the gluconeogenic pathway; as well as three growth-related genes, chitinase (CHI), ecdysteroid regulated-like protein (ERP) and juvenile hormone esterase-like carboxylesterase (JHEC). In addition, five antioxidant genes, including MnSOD, CAT, GPX, GST and nuclear factor E2-related factor 2 (Nrf2), were detected. The Primers were designed using the Primer 5.0 software  was used to analyze the relative expression levels of the genes [The differences in glucose metabolism, growth-related genes and antioxidant genes between the control group and the challenge group were analyzed using qPCR experiments. They mainly included three key genes, hexokinase . 100 mg of the muscle samples was weighed. The ratio of the sample to PBS was mixed at 1:9, and then the total protein content of the muscle was determined according to the instructions. The measurement process required incubation at 37 °C for 30 min, and the OD value was calculated at 562 nm.The determination of the hepatopancreas and muscle glycogen content was carried out using a liver/muscle glycogen assay kit . 100 mg of the hepatopancreas and muscle samples was weighed separately. The glycogen detection solution was prepared with a ratio of sample to alkali solution of 1:3, and boiled for 5 min. The OD value was measured and calculated using a wavelength of 620 nm. The above experiments were performed using an Infinite 200 PRO multifunctional enzyme marker .A glucose kit (glucose oxidase method)  was used to analyze the changes in the hemolymph glucose levels. The content of hemolymph glucose was measured directly in accordance with the instructions, and incubated at 37 °C for 10 min. Ultimately, the OD value at 505 nm was evaluated.2O were homogenized at a ratio of 1:9, diluted to a concentration of 10%, bathed in water for 10 min and the supernatant was collected for determination after centrifugation. 100 μL of the hemolymph sample was mixed with ddH2O at a ratio of 1:4, and the supernatant was also collected using centrifugation for detection. The OD value was measured and calculated using a wavelength of 636 nm.The ATP content was measured using an ATP assay kit . The hepatopancreas samples (100 mg) and ddHA lipid peroxidation assay kit  was used to determine the LPO content. The proportion of hepatopancreas to normal saline was homogenized at 1:9. Incubation was required at 45 °C for 60 min, and the OD value was measured and calculated using a wavelength of 586 nm.The MDA content was determined using a Malondialdehyde (MDA) Assay Kit . The tissue homogenate was prepared according to the instructions, incubated at 95 °C for 40 min and the OD value was measured and calculated using a wavelength of 532 nm.The growth of the shrimp in the control group and EHP challenge group was recorded, and the relevant growth indicators were calculated. They comprised initial weight, final weight, average daily weight gain (ADG), weight gain, feed conversion ratio (FCR) and survival rate.The above indicators referred to the method of Zarain-Herzberg et al. , where Ft-test was used to analyze the statistical significance at p < 0.05. All numerical data shown in the figures and tables are mean ± SE. Asterisks and double asterisks represented the statistically significant difference and the extremely significant difference between the challenge group and the control group, respectively.The data statistics were carried out using the SPSS 17.0 software. One-way analysis of variance and the 5 ± 1.51 × 105 EHP copies−1 ng HP DNA), followed by the 10th dpc (2.34 × 105 ± 1.25 × 105 EHP copies−1 ng HP DNA) and 5th dpc (3.30 × 104 ± 6.19 × 103 EHP copies−1 ng HP DNA).The infection of EHP in the control group and the challenge group was detected using PCR. The shrimp in the challenge group were EHP-positive after the 5th dpc, while the control group remained EHP-negative throughout the experiment. The EHP load was detected using qPCR, and the results showed that the maximum load appeared on the 20th dpc . At the same time, the results of the determination of the hepatopancreas glycogen and muscle glycogen showed that the hepatopancreas and muscle glycogen of the shrimp in the challenge group decreased significantly at the 5th dpc and 10th dpc (p < 0.05), and recovered to the control level at the 20th dpc (p < 0.05), and similarly, the ATP content of the hemolymph also decreased significantly at the 5th dpc, 10th dpc and 20th dpc (p < 0.05). Moreover, the hemolymph glucose content of the EHP-infected shrimp decreased significantly at the 5th dpc and 20th dpc (p < 0.05)  .HK and PK were significantly down-regulated at the 5th dpc and 20th dpc (p < 0.05), and PFK was significantly down-regulated at the 5th dpc, 10th dpc and 20th dpc (p < 0.05). The key genes CS and IDH in the TCA cycle were significantly down-regulated at the 5th dpc, 10th dpc and 20th dpc compared with the control group (p < 0.05). However, the key genes in the gluconeogenesis pathway were up-regulated to a certain extent after EHP infection. The expression level of PEPCK was increased at the 5th dpc and 20th dpc, of which it was significantly up-regulated at the 5th dpc (p < 0.05). The expression of FBP increased significantly at the 10th dpc and 20th dpc (p < 0.05). G6P was significantly up-regulated at the 5th dpc and 10th dpc (p < 0.05) (CHI was significantly down-regulated during the experiment (p < 0.05). JHEC was significantly down-regulated at the 5th dpc and 20th dpc (p < 0.05). However, ERP was significantly up-regulated at the 5th dpc and 20th dpc (p < 0.05), but the difference was not significant at the 10th dpc  . In addi10th dpc .SOD, GPX and GST and the antioxidant pathway factor Nrf2 of the shrimp in the EHP challenge group were significantly up-regulated at the 10th dpc and 20th dpc (p < 0.05). However, CAT was only significantly up-regulated at the 10th dpc (p < 0.05) (p < 0.05) (The results of qPCR showed that the antioxidant enzyme genes  < 0.05) . Overall < 0.05) .p < 0.05). Moreover, the ADG of the shrimp in the challenge group (118.06 ± 17.0 mg) was significantly lower than that in the control group (222.50 ± 11.5 mg) (p < 0.05), while the FCR of the challenge group (2.82 ± 0.21) was significantly higher than that in the control group (1.49 ± 0.06) (p < 0.05). However, the survival rate of the challenge group (76.67%) was lower than that of the control group (93.34%) . At the same time, the weight gain of the shrimp in the challenge group (2.36 ± 0.34 g) was significantly lower than that in the control group (4.46 ± 0.23 g) ((93.34%) . Equally(93.34%) A,B.5 ± 1.51 × 105). This suggests that there is a positive correlation between the degree of hepatopancreas damage and the severity of infection. Compared with a healthy hepatopancreas, these symptoms indicate that the normal absorption and digestion functions of the hepatopancreas are impaired, which may result in the inability of the hepatopancreas to provide nutritional support for the normal growth and development of the shrimp.The hepatopancreas of crustaceans integrates the functions of the mammalian liver and pancreas, and is an important organ for nutrient storage, synthesis and digestion. The hepatopancreas, as the main target organ of EHP, even plays an important role in regulating the secretion of growth-related hormones in crustaceans ,37, whicNephrops norvegicus  infected with parasitic dinoflagellates [As an important nutrient, protein is considered the main source for animal growth and development. This study found that EHP infection caused a decrease in the total protein content of muscle, which may be closely related to the hepatopancreas damage directly caused by EHP parasitism. This further indicates that EHP interfered with the normal muscle development and affected the molting process of the shrimp, resulting in growth retardation . Similargellates . It is pgellates ,46.HK, PFK and PK are important key regulatory enzymes in the glycolytic pathway, and changes in their expression affect the entire pathway [PFK is considered to play a restrictive role in the pathway, determining the rate and direction of the reaction [PFK, which means that the capacity of anaerobic metabolism decreased, the metabolic rate slowed down and the metabolic process changed. Meanwhile, the key regulatory enzymes in the TCA cycle, CS and IDH, were significantly down-regulated. As the primary key regulatory enzyme of the TCA cycle, CS controls the speed of acetyl-CoA entering the TCA cycle and releasing ATP via oxidative phosphorylation [IDH, another key regulatory enzyme in the TCA cycle, catalyzes the oxidative decarboxylation of isocitrate into 2-oxoglutarate and releases ATP via the electron transport chain [FBP is a rate-limiting enzyme for gluconeogenesis, which controls the rate of gluconeogenesis and catalyzes the conversion of fructose-1,6-diphosphate into fructose-6-phosphate [FBP expression was significantly increased at the 10th dpc and 20th dpc, and the expression of key enzymes PEPCK and G6P was also up-regulated, indicating that the gluconeogenesis process was enhanced. Since the parasitism of EHP needs to continuously absorb the energy from the host to maintain its own proliferation, the host is in a state of starvation [Vibrio parahaemolyticus, the glucose metabolism process in vivo was significantly enhanced [Whether carbohydrate metabolism is normal or not can affect the molting and growth process of crustaceans, as well as the ability to cope with hypoxia stress and the invasion of pathogenic microorganisms ,48,49. C pathway . The expreaction ,53. EHP rylation . IDH, anrt chain . The decrt chain . If the hosphate . After Earvation . This siarvation . It is parvation  or Vibrienhanced . WSSV inenhanced ,60. PerhSOD, CAT, GPX and GST [MnSOD is mainly distributed in the mitochondria and can catalyze the decomposition of superoxide into oxygen and hydrogen peroxide. Previous results found that the transcription level of MnSOD increased significantly after shrimp were injected with the pathogen [MnSOD and GPX were detected at the 10th dpc and 20th dpc, suggesting that EHP activated the antioxidant defense system of the shrimp. In addition, the body produces a large amount of ROS, which can induce the expression of antioxidant genes, and in turn protect host cells to reduce oxidative damage [CAT is consistent with that in SOD, which is responsible for the decomposition of hydrogen peroxide into oxygen and water. However, CAT was significantly elevated only at the 10th dpc. It may be because both CAT and GPX perform the function of decomposing peroxides, but GPX is more sensitive to peroxides in the body and can play a role even at low concentrations. This was verified using nitrite stress experiments [GPX has the function of detoxification metabolism, which is considered to be more important than CAT. Importantly, GPX in shrimp can be induced by Vibrio alginolyticus [GST also increased significantly in this experiment, suggesting that it may participate in the transport of endogenous substances and play an irreplaceable role in detoxification and cell protection [Nrf2-Keap1 signaling pathway is the most important antioxidant pathway in the body, and can regulate the activity of antioxidant enzymes [P. vannamei. It has been reported that inhibiting the expression of Nrf2 resulted in a significant decrease in the expression of related antioxidant genes  in shrimp [Nrf2 was significantly up-regulated after EHP infection, which was consistent with the expression of antioxidant enzymes, indicating that this gene may regulate the expression of antioxidant genes. Nrf2 has also been reported to be significantly activated in the response of P. vannamei to Vibrio harveyi [Oxidative stress is induced by excessive accumulation of free radicals and reactive oxygen species (ROS) in the body, which is an important factor leading to apoptosis and disease. It can be caused by stressors in vivo or in vitro. In order to prevent the damage caused by ROS, organisms have evolved an antioxidant defense system, with enzymatic responses to oxidative stress as the main strategy . Therefo and GST . MnSOD ipathogen . Similare damage . Usuallyeriments ,66. Meanolyticus . The expotection . The Nrf enzymes . Unfortun shrimp . In this harveyi . In addi harveyi . In orgaJHEC, ERP and CHI play important regulatory roles in molting, growth and reproduction in crustaceans. In this experiment, JHEC (at the 5th dpc and 20th dpc) was significantly down-regulated, whereas ERP (at the 5th dpc and 20th dpc) was significantly up-regulated. JHEC is a key enzyme in the degradation of methyl farnesoate (MF) [JHEC reduced the degradation rate of MF, resulting in stunted growth and development. The increase in ecdysterone is conducive to molting, but there is a negative regulatory relationship between ERP and ecdysterone. When the level of ecdysterone is high, the expression of ERP is inhibited, and the up-regulation of ERP in the present study was manifested as a delayed molting process [CHI can digest chitin, and the enhanced activity of this enzyme before molting can ensure a smooth molting process by decomposing the old shell [CHI, indicating that shrimp molting was blocked. Therefore, the parasitism of EHP destroys the normal substance metabolism in shrimp, resulting in insufficient energy for cell growth and development. Furthermore, EHP invasion breaks the balance between growth and molting-related hormones, which may be an important cause of retarded development of shrimp.The present study also demonstrated that EHP can lead to the abnormal expression of growth-related genes, among which ate (MF) . The red process ,75. Concld shell ,77. Howep < 0.05) due to the disruption of nutrient absorption and transport, indicating that the shrimp infected with EHP could not adequately absorb the nutrients in the feed. Fortunately, the administration of 5-aminolaevulinic acid and linolenic acid to EHP-infected shrimp could improve the function of the hepatopancreas to a certain extent [EHP can significantly damage the hepatopancreas of shrimp, disrupt the normal intestinal flora and cause nutrient absorption and transport disorders. Therefore, the final body weight and ADG of shrimp in the EHP challenge group were significantly lower than those in the control group. Similarly, this phenomenon of different individual sizes is more obvious in aquaculture ponds . In addin extent ,79. In an extent , taura sn extent  and whitn extent . Previoun extent ,81. ConsIn this study, the changes in hepatopancreas histology and the effects of EHP on the metabolism, oxidative stress and growth-related genes of healthy shrimp and EHP-infected shrimp were analyzed using EHP challenge experiment. Our studies have shown that the hepatopancreas became damaged with an increasing duration of EHP infection, and the degree of damage was positively correlated with the intensity of infection. At the same time, EHP infection affected the normal metabolism of substances and growth, which was characterized by the inhibition of glycolysis and the TCA cycle, activation of the gluconeogenesis pathway, and interference with the expression of growth-related genes. Furthermore, EHP induced oxidative stress in shrimp and resulted in the accumulation of a large amount of the lipid peroxidation products LPO and MDA, which was also an important cause of oxidative damage to the hepatopancreas. Additionally, severe EHP infection may result in white feces. In summary, this study concludes that EHP infection can disrupt the metabolic process of shrimp and cause oxidative stress, both of which will lead to the slow growth of shrimp and even death in severe cases.


One Health Approach,” a system incorporating a multidisciplinary effort to achieve the best possible health outcome by acknowledging the clear connections between humans, animals and their shared environment. The importance of public awareness and health literacy of lay audiences still needs to be further emphasised as part of global and local action plans. Antimicrobial resistance continues to be a major global public health dilemma of the 21st century. Already this topic is receiving substantial political input from the G7 countries and continues to be on the agenda of numerous political conferences. The consequences of failure to adequately address AMR are profound, with estimations of a return to the pre-antibiotic era, where everyday infections relating to childbirth, surgery and open fractured limbs could be potentially life-threatening. AMR itself represents a microcosm of factors, including social anthropology, civil unrest/war, diasporas, ethnic displacement, political systems, healthcare, economics, societal behaviour both at a population and individual level, health literacy, geoclimatic events, global travel and pharmaceutical innovation and investment, thus finding a solution that adequately addresses AMR and which helps stem further AMR emergence is complicated. Success will involve individuals, communities and nations all working together to ensure that the world continues to possess a sufficient armamentarium of effective antimicrobials that will sustain human and animal health, both now and in the future.Antimicrobial resistance (AMR) has now emerged as a chronic public health problem globally, with the forecast of 10 million deaths per year globally by 2050. AMR occurs when viruses, bacteria, fungi and parasites do not respond to antimicrobial treatments in humans and animals, thus allowing the survival of the microorganism within the host. The prominent cause contributing to the current crisis remains to be the overuse and misuse of antimicrobials, particularly the inappropriate usage of antibiotics, increasing the global burden of antimicrobial resistance. The global consumption and usage of antibiotics are therefore closely monitored at all times. This review provides a current overview of the implications of strategies used by international governmental organisations, including the UN’s 17 Sustainable Development Goals (SDGs), to address the problem of antibiotic resistance, as well as the “ Silent Pandemic” and is a problem where urgent action is needed immediately and should be managed more effectively and not be considered as a future situation [Antimicrobial Resistance (AMR) results when microorganisms including bacteria, fungi, parasites and viruses evolve to the extent that they eventually become resistant to the antimicrobial medications, such as antibiotics, which are used to treat such conditions . AMR hasituation .Without preventative measures, it is estimated that by 2050, AMR could potentially become the world’s primary cause of death [One Health Approach” was introduced which requires a global collaborative effort to involve a number of different disciplines: the Food and Agriculture Organization of the United Nations (FAO) and the World Organization of Animal Health (OIE), to ensure that each agency works within its speciality and with other agencies to minimise the potential effects of AMR [In response to AMR, several global health organisations and governments have taken action to combat this issue. The “s of AMR . In addis of AMR .Within most of these newly proposed measures, one of the most effective approaches is to increase public awareness of the AMR pandemic as a preventative strategy, thereby requiring good communication with all stakeholders . In thisThe creation of antimicrobials is one of the most effective drug treatments in medical history. The introduction of antimicrobials has helped to manage and greatly reduce death rates caused by infectious diseases, previously the leading cause of death in humans . Human lPrevious research has shown that one of the main causes of AMR is the inappropriate and excessive use of antibiotics, both in humans, as well as in animals. Since the 1950s, when the “golden era” of antibiotics began, Alexander Fleming had expressed concerns about the potential emergence of resistance if treatment is used for an inadequate amount of time . “Since As a result, the use of antibiotics in treating infectious diseases and other conditions has become widespread in modern medicine. Nevertheless, the misuse and even over-prescription of these antimicrobials has fast outpaced their efficacy as AMR has grown markedly .A series of recent studies have indicated antimicrobial involvement in agriculture and food systems may have a significant impact on driving AMR . AccordiIn addition, zoonosis also poses a serious transmission factor of AMR, where antibiotic-resistant bacteria are spread between animals and humans, through either direct or indirect interaction, as well as through foodborne or waterborne events , 18.E. coli isolates from animal and commercial meat sources and MCR-1 is believed to have been widely transmitted in food-producing animals in south China. In contrast, relatively low MCR-1 was detected from human origin, this difference in the prevalence of MCR-1 between animals and humans is likely to be a form of zoonotic transmission from animals to humans [A study conducted in China has reported that mediated colistin resistance (MCR-1) poses a high risk to AMR due to zoonosis transmission from animal to human . Accordio humans .Colistin is regarded as a “last resort” antibiotic that is increasingly being utilised to treat patients with multiresistant bacteria, although it is still effective it was not typically used to treat common infections due to its potentially adverse side effects. However, if colistin resistance evolves rapidly, these bacterial infections may be more difficult-to-treat .The lack of knowledge of antimicrobials is also a major contributing factor to AMR. Public Health England conducted a UK survey in 2017 to find out public knowledge on antibiotics . Eighty With AMR emerging at a rapid rate, the infection and death rates of AMR are closely monitored at all times. In the United Kingdom, the estimated AMR infection rate was 65,162 people diagnosed in 2019, which increased from 61,946 patients recorded in 2018 . In compPrevious literature focusing on the different national responses to antibiotic resistance highlighted the key risk factors contributing to AMR between developing and developed countries and how each lead to AMR in a different manner. Several AMR contributing factors were found in developing countries which include, poor regulation control of antimicrobial drugs, insufficient monitoring of the emergence of AMR, inappropriate use of antibiotics in clinical settings and the inadequate quality check for antibiotics supplied .Recent studies on the accessibility of antibiotics in low- and middle-income countries found that Vietnam and Bangladesh had the highest proportion of unlicensed locations where antibiotics are administered, with relevant antibiotics frequently found in typical drug stores for mild illnesses, where they are widely available to the general public . Since tOn the contrary, in developed countries, the risk factors that exist in developing countries may not necessarily apply. These include the excessive use of antimicrobials in agricultural use and over-prescription in clinical settings . ResearcThere is now a growing body of research that investigates global antibiotic consumption. The Global Research on Antimicrobial Resistance (GRAM) Project, conducted the first known long-term study to estimate the global consumption of antibiotics, which covered 204 nations from years 2000–2018. According to this estimation of the average daily dose, a significant increase of 46% in the global antibiotic consumption rate was observed throughout this period of time .This seminal study through employment of a spatial disparities/geostatistical model, identified large national and subnational variations of antibiotic usage in Low- and Middle-income countries (LMICs), with the lowest levels in sub-Saharan Africa and the highest in eastern Europe and central Asia . The stuDespite that, critics have also argued that this is not the only problem but an addition to issues of increased “last line antimicrobials” consumption. According to recent research, last-line antibiotics such as polymyxin consumption in humans has increased by 67% in the EU/EEA and these last-line antibiotics are typically prescribed in hospital settings to treat patients suffering from serious infections as a last resort to combat multidrug-resistant bacteria . As a reThis ongoing pattern has presented a strong correlation between AMR and antibiotic consumption. Several studies have supported this view, including a longitudinal study which reported a significant strong association between the use of antibiotics, particularly carbapenems and carbapenem resistance . SimilarHowever, issues of the debate are a concern as previous studies have argued that a direct correlation may not be present between antibiotic consumption and AMR since other factors were ignored during the research. Many of these correlation studies were conducted in hospitals where patients are presented with underlying problems, the results of the correlation may be overstated . FurtherAntibiotic usage also influenced AMR in relation to the difference between LMICs and High Income Countries (HICs), resistance maps of global usage of antibiotics were collected worldwide from the years 2000–2015 . A distiSince there is evidence of a correlation between the overuse of antibiotics and the development of AMR, reducing antibiotics usage could be a beneficial goal in HICs, with over usage of antimicrobials. In contrast, increasing the accessibility of such antimicrobial medication remains a goal for many LMICs, as the death rate remains high caused by infectious diseases in many LMICs due to the lack of effective antimicrobials access to those in need . In a stWhile there is ongoing research on new antimicrobial treatments, there must be controls and management of the antibiotics including standardisation of quality checks and accessibility of antibiotics. Therefore, improving surveillance programs is urgently required in some LMICs to improve the current state of AMR.One Health” embraces the concept that there is a clear connection between the health of both humans and animals and the shared surrounding environment as shown  and the World Organization of Animal Health (OIE) to ensure effective actions are taken from all sectors in reducing the risks of AMR from this approach [The “approach .A growing number of studies have shifted their attention from human factors to more serious contributing AMR factors arising from animal aspects. Earlier research indicated that 73% of all antibiotics used worldwide are used in farm animals, largely for food production . This woAdditionally, the agriculture sector is taking a proactive role in ensuring the responsible use of veterinary medicines, through the development of various antimicrobial stewardship programmes. RUMA (Responsible Use of Medicines in Agriculture Alliance) encourages innovative and proactive efforts to improve the responsible use of veterinary medicines while ensuring optimum animal health and welfare .One Health” emphasises the interdependence of human and animal health [Additionally, the idea of “l health , 44. Thel health . This apOne Health Approach” on AMR is rather challenging to be successfully conducted in LMICs compared to HICs. LMICs still remain to be the most affected by AMR as to facing more serious challenges that do not apply in HICs such as poverty, corruption and healthcare systems leading to a more disease-prone environment such as lack of clean water access and sanitation issue and even the accessibility of antimicrobials [The implication of the “crobials . A previcrobials . Howevercrobials . This deOne Health Approach,” especially in LMICs, by possibly introducing antimicrobial-sensitive intervention such as clean water access, this approach would be more cost-effective and sustainable in some resources limited LMICs.Several approaches can strengthen this “One Health Approach,” in 2015, the WHO launched an AMR-related management program known as the Global Action Plan focusing on AMR (GAP-AMR). This plan aims to ensure that infectious disease can always be successfully treated and prevented by preserving antimicrobials in a responsible manner with appropriate accessibility and quality checks [In addition to the “y checks .Five main objectives were established to fulfil this goal, one of which is to enhance the efficacy of antimicrobial medication use for both human and animal health, this would require a good regulatory system, respectively . Some ofIt is expected that countries would introduce their national plans in AMR in order to reach the goals of the overall Global Action Plan. According to the WHO, 18 countries and territories have established multi-stakeholder national action plans on AMR while six countries are in the final stages of creating national action plans .The other approach launched was the Global Antimicrobial Resistance and Use Surveillance System (GLASS). The aim of this program is to focus on promoting surveillance of AMR globally and determining the causes of AMR. This would involve providing advice and guidance to support nations to implement remedial measures as necessary .The occurrence of the COVID-19 pandemic in 2020 created an unprecedented scenario for the treatment of suspected or proven bacterial infections with antibiotics. The changing dynamic in the movement of patients within healthcare , largely driven by the patients’ SARS CoV-2 status, combined with reduced diagnostic ability due to redeployment of laboratory staff to SARS CoV-2 testing, resulted in a temporary redefining of “Best Practice” antimicrobial stewardship programmes, due to pandemic-related constraints. A recent study investigating global antibiotic use during the pandemic, through examination of pharmaceutical sales data from 71 countries during the years, 2020–2022, showed that sales of cephalosporins, penicillins, macrolides, and tetracyclines decreased dramatically during April–May 2020, afterwhich there was a gradual rise to nearly pre-pandemic rates through May 2022 . This stPercentage of bloodstream infections due to selected antimicrobial-resistant organisms.” The WHO have indicated that AMR impacts seven of the 17 SDGs, as detailed in As part of the 2030 Agenda for Sustainable Development, the United Nations has published 17 Sustainable Development Goals (SDGs) including many aspects of societal and human interactions, as illustrated in The clinical microbiology laboratory, as well as biomedical scientists, have an important role to play in combatting AMR, both locally and internationally. Diagnostics play a vital role in adding value in terms of 1) laboratory surveillance of AMR epidemiology, through monitoring, 2) providing antimicrobial susceptibility results for clinically significant pathogens, to help avoid empirical antibiotic prescribing, but rather evidence-led antibiotic selection, 3) helping to determine if the aetiology of clinical infections are viral or bacterial, thereby helping decide the potential value of intervening with antibiotics, 4) providing innovative techniques to robustly allow more rapid turnaround times for reporting of antimicrobial susceptibility results to antibiotic prescribers, so that good antimicrobial stewardship practices are promoted and 5) allowing the elucidation of novel mechanisms of antimicrobial resistance, through whole genome sequencing techniques. Recent advances in biomedical science innovative has allowed the development of total laboratory automation for the rapid detection and identification of pathogens, as well as for the determination of their antimicrobial susceptibility . AdditioAMR places new challenges for the clinical diagnostic laboratory. Our group recently reported that traditional microbiological agar formulations may become less efficient in their selective properties due to breakthrough of AMR organisms, where current concentrations of antibiotics have become ineffective in containing breakthrough from AMR organisms . The emePseudomonas aeruginosa, overgrowing agar cultures designed for the detection of Mycobacterium tuberculosis [One example of this is the growing problem of highly resistant organisms, especially rculosis .Antimicrobial resistance continues to be a major global public health dilemma of the 21st century. Already this topic is receiving substantial political input from the G7 countries and continues to be on the agenda of numerous political conferences. Adoption of mitigating strategies are beginning to see positive results, with tangible outcomes see . However


The emergence and rapid spread of antimicrobial resistance (AMR) pose a grave threat to public health globally, and particularly so in India. With its unique combination of a dense population, a significant disease burden, and diverse healthcare practices, India stands at a critical juncture in the global battle against AMR. The implications of this escalating crisis are far-reaching, threatening decades of medical progress, undermining healthcare delivery, and posing potential roadblocks to the realization of several Sustainable Development Goals.AMR is a crisis within the Indian healthcare system as it severely hampers the effective treatment of infectious diseases, leading to higher mortality rates, longer hospital stays, and increased healthcare costs. Its rise could mark the return of the pre-antibiotic era, where common infections and minor surgeries could once again become life-threatening. Addressing the challenge of AMR in India requires a comprehensive, multifaceted, and well-coordinated response. From creating strong regulatory frameworks for antibiotic usage and improving diagnostic capabilities to fostering greater public awareness and promoting research into new antimicrobials, the strategies need to be as diverse and interconnected as the problem itself.This editorial will delve into the specificities of the AMR challenge within the Indian healthcare system, discuss potential strategies for mitigating the crisis, and evaluate the broader implications for public health and national policy. It will also highlight why India's response to this global health threat is crucial not only for the country but for the world at large. Klebsiella pneumoniae's susceptibility to imipenem has decreased from 65% in 2016 to 43% in 2021, while Escherichia coli's susceptibility to imipenem has decreased from 86% in 2016 to 64% in 2021 [Escherichia coli and Klebsiella pneumoniae that are resistant to carbapenems were also resistant to other antimicrobials, making it difficult to treat carbapenem-resistant infections. In addition, they found that in 87.5% of study participants, Acinetobacter baumannii infections were resistant to the broad-spectrum antimicrobial carbapenem, reducing the number of available treatment choices. Similarly, a study by Sharma et al. found that the sensitivity of Klebsiella pneumoniae to meropenem decreased from 15% in 2018 to 2.5% in 2022, while the sensitivity of Klebsiella to colistin decreased from 96% in 2018 to 28% in 2022 [The phenomenon of antimicrobial resistance (AMR) refers to the ability of microorganisms, such as bacteria, viruses, fungi, and parasites, to evolve and become resistant to the drugs that were previously effective against them. This resistance primarily stems from the misuse and overuse of antimicrobials in humans, animals, and even in the environment. The Indian Council of Medical Research (ICMR) annual report of 2021 found that While AMR is a widespread issue across India, the patterns and causes of resistance can differ between rural and urban areas due to various socio-economic, environmental, and healthcare-related factors . In urbaIn contrast, rural areas may have different drivers of AMR. While there may be less access to antibiotics in general due to the lower availability of healthcare services, misuse can still occur due to a lack of awareness about the correct use of antibiotics. Over-the-counter sales of antibiotics without a prescription, a common practice in India, may be particularly widespread in rural areas where healthcare access is limited. Furthermore, the use of antibiotics in agriculture, including in livestock, can be a significant driver of AMR in rural areas. Rural-urban migration can also contribute to the spread of AMR between these areas. People moving from rural areas to cities can bring resistant bacteria with them, while people returning to rural areas after receiving medical treatment in cities can introduce resistant bacteria into these rural settings.AMR patterns can vary between the private and public healthcare systems in India due to differences in practices, policies, and resources available in each sector . In privOn the other hand, the public healthcare system often faces resource constraints, which can affect the availability and usage patterns of antibiotics. In some cases, this can lead to the inappropriate use of antibiotics due to the unavailability of the most appropriate ones. Public hospitals usually have a higher patient load, and the sheer number of patients might sometimes result in less personalized care. This could lead to a lack of follow-up on antibiotic courses and potential misuse. In public hospitals, especially in lower-tier cities and rural areas, infection control practices may not be as robust as in private hospitals. This can lead to the spread of drug-resistant infections within the healthcare facility. Patients in public hospitals often come from lower socio-economic backgrounds, and their previous exposures to antibiotics (often without prescription) can impact the AMR patterns seen in these settings.The future of AMR in India, as in other parts of the world, will depend heavily on the measures taken to address this issue at the individual, community, national, and international levels . To tack


It was demonstrated that the essential parameters affecting stereocomplexation are the mixing ratio and the chain length of each unit sequence. This study deals with the molecular weight, one of the specific interactions between isomers of PLAs. A solution polymerization method was applied to control molecular weight and chain architecture. The stereocomplexation was monitored with DSC. It was confirmed that the lower molecular weight polymer showed a higher degradation rate, as a hydrolyzed fragment having a molecular weight below a certain length dissolves into the water. To systematically explore the critical contribution of molecular weights, the Langmuir system was used to observe the stereocomplexation effect and the overall degradation rate.Polylactides (PLAs) and lactide copolymers are biodegradable, compostable, and derived from renewable resources, offering a sustainable alternative to petroleum-based synthetic polymers owing to their advantages of comparable mechanical properties with commodity plastics and biodegradability. Their hydrolytic stability and thermal properties can affect their potential for long-lasting applications. However, stereocomplex crystallization is a robust method between isomer PLAs that allows significant amelioration in copolymer properties, such as thermal stability, mechanical properties, and biocompatibility, through substantial intermolecular interactions amid  For several decades, conventional petroleum-derived synthetic polymers have been favored materials extensively employed in various industrial and consumer applications. This preference is primarily due to their remarkable mechanical strength, toughness, long-term stability, and cost-effectiveness ,2. Howevco-terephthalate) (PBAT) have been identified among various options. These polymers are capable of undergoing degradation through ester bond cleavage under acidic, basic, or enzymatic conditions [l-lactide) (PLLA) and poly(d-lactide) (PDLA), which can prevail from both melt and solution blending [Promising biodegradable polymers such as polylactide (PLA), poly(butylene succinate) (PBS), poly(3-hydroxybutyrate), and poly 2-ethylhexanoate, proteinase K, and Tris(hydroxymethyl)amino-methane were obtained from Sigma-Aldrich, located in St. Louis, MO, USA. Solvents such as toluene, chloroform, methanol, n-hexane, and hydrochloric acid were purchased from Samchun, a supplier in Pyungtaek, Republic of Korea. All chemicals were utilized as received without additional purification.Enantiomeric PLAs were synthesized by solution polymerization at 70~120 °C in toluene for 12~48 h using tin(II) 2-ethylhexanoate (0~10 wt% of lactide) as a catalyst in a nitrogen atmosphere. This method allows synthesizing PLA directly from the lactide monomer and can produce a desired molecular weight by varying the amount of catalyst, polymerization temperature, and reaction time . This prThe polymerization of LA was performed in toluene, and the initial concentration of the monomer was 30 wt%. A high concentration of the catalyst is typically used to initiate the faster reaction kinetics, leading to shorter reaction times and higher polymerization yields. It is difficult to control the molecular weight for a lower catalyst concentration (<1 wt%) as the number of reaction sites decreases dramatically, making it difficult to proceed with the reaction. Lower catalyst concentrations can slow down the reaction rate, resulting in longer polymerization times. This can be advantageous when aiming for specific molecular weights or controlling the polymerization process more precisely. By reducing the catalyst concentration, the reaction can proceed at a slower pace, allowing for better control over molecular weight, polymerization extent, and final PLA properties. The ring-opening polymerization in solvent was conducted at 100 °C for several hours under an inert atmosphere because the polymerization at a low reaction temperature below 80 °C did not occur. However, the evaporation of the solvent occurs too quickly, with or without reflux, when the reaction temperature surpasses 110 °C, which makes polymerization difficult. It indicated that solution polymerization is an easier process than bulk polymerization for controlling the molecular weight of PLA. Although many factors are accounted for to perform the polymerization, they require various trials and errors. The polydispersity index (PDI) of PLAs synthesized by solution polymerization was much narrower than that of bulk polymerization due to the minimization of chain transfers. A lower PDI indicates a more narrow and homogeneous distribution of molecular weights in the synthesized polymer. A PDI below 2 suggests that the majority of polymer chains have similar lengths, resulting in a more uniform material. This can be advantageous in various applications, as it indicates a higher level of control over the polymerization process and a more consistent product.n-hexane as non-solvents. Subsequently, the products were kept for drying at 25 °C for about three days. For studying enzymatic degradation, a spin coating process was used for making thin films with 5 wt% polymer solution, and 1 μmol/mL polymer solution was spread on a subphase for the Langmuir film.After the solution polymerization, a rotary evaporator was used to remove the excess solvent. The obtained polymers were purified by the dissolution/precipitation method using chloroform as a solvent and methanol and n) and PDI (Mw/Mn). The GPC system used was the CBM-20A, DGU-20A3, LC-6AD, SIL-20ACHT, CTO-20A, RID-10A by Shimadzu Corp. The analysis was performed in chloroform at a flow rate of 1.0 mL/min at a temperature of 40 °C. Polystyrenes from Showa Denko K.K. (Shodex® STANDARD SM-105) were employed as standard references. The thermal properties of the samples were assessed using a differential scanning calorimeter  under a nitrogen atmosphere, with a heating rate of 10 °C/min. 3, KSV-NIMA Langmuir probe system, Biolin Scientific) was stabilized for one hour and filled with approximately 500 mL of deionized water. The solution, typically 100 μL of 1 μmol/mL concentration, was spread on the water surface for surface pressure-area (π-A) isotherm and kinetic measurements, unless otherwise specified. The solvent was allowed to evaporate for 1 min, as determined based on the reproducibility of the π-A curve. The compression rate of the barriers was maintained at 10 cm2/min for all experiments. Scanning electron microscopy (SEM) was employed to obtain surface morphological images using the Tescan-MIRA3 microscope from the Czech Republic.The gel permeation chromatography (GPC) analysis was conducted to determine the average molecular weight (MThe buffer solution was prepared with deionized water and 0.1 M Tris(hydroxymethyl) aminomethane. The pH of the solution was adjusted to 8.6 with the addition of hydrochloric acid. Enzymatic degradation experiments were conducted using proteinase K, with 0.02 mg and 0.1 mg enzyme quantities in the buffer solution at room temperature for monolayer and thin film experiments, respectively. PLLA and PDLA homopolymer solutions in chloroform were prepared by vigorously stirring for 24 h at a concentration of 1 μmol/mL, and each solution was mixed. The Langmuir trough was stabilized for 1 h and then filled with approximately 500 mL of deionized water. After spreading the polymer solution, a waiting time of over 1 min was employed, determined based on the reproducibility of the π-A curve, allowing the solvent to evaporate.For the investigation of enzymatic degradation on spin-coated samples, a cuvette containing 1 mL of buffer solution with an enzyme concentration of 0.1 mg/mL was used. After degradation, the samples were washed with distilled water and dried at 25 °C for 24 h.5 g/mol, beyond which the formation of stereocomplexes becomes challenging [As mentioned above, the synergistic effect on the mechanical and thermal properties can be achieved by the stereocomplexation between the isomers of PLA. There are some factors that influence the stereocomplexation, such as molecular weight, blending conditions and ratios, and optical purity. However, achieving a perfect stereocomplexation without any homocrystallization of PLLA or PDLA is not possible in all blends with low, high, or medium molecular weights. The molecular weights of PLLA and PDLA play a significant role in determining the competition between the formation of stereocomplexes and homocrystallites in their enantiomeric blends . There illenging . Since bAdditionally, the hydrolytic degradation and enzymatic degradation (from proteinase K) of stereocomplex PLA are more delayed than PLA. In this study, the effect of the molecular weight of each component on stereocomplex formation was systematically investigated. Four (PLLA/PDLA) blend systems, LL, LH, MH, and HH, were selected as shown in m) of all synthesized PLA. As shown in m of PLA increased monotonously with its molecular weight. The Tm of semicrystalline polymers can be enhanced up to a critical molecular weight, and afterward, the Tm is not affected noticeably. All homopolymers such as PLLA5, PLLA15, PLLA84, PDLA9, and PDLA90 depicted single endothermic peaks at around 136 °C, 163 °C, 175 °C, 153 °C, and 178 °C, respectively. The Tm of PLLA5 was much lower than the Tm of other PLA isomers. The DSC thermograms in DSC was used to determine the melting temperature  to 15 k (MH), Tsc of MH is ca. 10 °C higher than that of LH, but Tsc of HH (Mn of PLLA: 85 k) slightly increases. Therefore, the critical Mn value of the isomer for stable complexes is around 15 k. However, the degree of complexation increases as Mn decreases, which is attributed to their enhanced mobility in solvents or melts. When the Mn of polymers, such as PLA, is higher, the polymer chains become longer and more entangled. As a result, the mobility of the polymer molecules decreases. This reduced mobility affects the ability of the polymer chains to form stereocomplexes, which are complexes formed between the PLLA and PDLA isomers. In the case of stereocomplex formation, the PLLA and PDLA isomers have a higher tendency to associate and form complexes at lower molecular weights because the chains have greater mobility. However, as the molecular weight increases to some critical point, the entanglement of the polymer chains restricts their movement and reduces their ability to form stereocomplexes.Jun Shao et al. stated that when the molecular weight of PDLA was lower than that of PLLA, the crystallites were formed more because of the high mobility of PDLA, which results in a lower Tm for stereocomplexes even with high mobility . Similarsc for stereocomplexes. The lamellar thickness increased with molecular weight, and viscosity was also enhanced. The viscosity of the solution plays a prominent role in the formation of the stereocomplex [sc (236.7 °C) was observed in the HHStereo blend, which can be attributed to the similarity in sequence length between both isomers within the same molecular weight range and the potential for the thickest stereocomplex crystal lamellae. The high molecular weight of the PLLA was estimated to be the high-molecular-weight chain of PDLA, which results in a prolonged crystal period and a higher Tsc of the stereocomplex. However, the Tm of LPLLA was much lower than other PLA isomers, but the Tsc of the blends has not been observed. It depicts that the chain length of LPLLA is long enough to complex with LPDLA and HPDLA.However, stronger chain mobility and thin lamellar thickness of the low molecular weight PLA isomers (LLStereo) were observed to lower the Tocomplex ,27,28. Tsc are decreased at first and then rapidly increased when the molecular weight of PLLA and PDLA increased, while Xsc is first decreased, then increased, and again decreased as the molecular weight of PLLA and PDLA increased  increases as the molecular weight of the isomers increases, indicating successful stereocomplexation.In the PLLA/PDLA blend films , both Tsncreased . Tsc wasort time . Howeverort time . Alterna2/repeating units. Additionally, both polymers illustrate more expanded and compressible monolayers, possessing at low surface pressure a limiting area of about 50 Å2/repeating units. The corresponding isotherm of high molecular weight (HPLLA) reveals a longer and flatter plateau than the PLLA with low molecular weight (LPLLA). Specifically, in the PLLA with high molecular weight (HPLLA), intense phase transition behavior was seen, in which the surface pressure was constant.The π-A isotherms, which depict the relationship between surface pressure and mean molecular area, provide insights into the lateral interactions between molecules in Langmuir monolayers. In Stereo) shows an increment in the area occupied by the two oligomer molecules, the phase transition behavior was divided into two sections at 7 mN/m and 16 mN/m. More specifically, it shows a short plateau, and the transition is comparable to one of the second plateaus, signifying the surface pressure does not remain constant and the molecular chain is too short to form a complete stereocomplex (the limit of entanglement).This difference was also evidenced in the stereocomplex curve. The corresponding isotherms of high-molecular-weight polymer blends (HHStereo) depict one-phase transition behavior above the PLLA homopolymers (12 mN/m). The phase transition intervenes at an approximately constant surface pressure with the longer and flatter plateau, which means that the area occupied by the polymer chains increased because of the interaction between the two molecules. Although the blend of low-molecular-weight isomer PLA  during an initial stage. It is due to the polymeric monolayers needing some time to be stable conformationally at the air/water interface when a surface pressure reaches a desired constant one. After that, monolayers are stable, and the A/A0 ratio is constant. However, LLStereo showed distinctly different characteristics as it contained very low-molecular-weight PLA isomers. As per the DSC results, LLStereo formed a complete single stereocomplex peak over 200 °C, but it showed a 25% reduction in the area occupied by the monolayer chain over 200 min, even though the decreasing rate of A/A0 is slower with time. Unlike the PLLA homopolymer, where complete degradation occurred in 100 min, LLStereo was able to delay the degradation rate if we consider that 50% of monolayers are LPLLA. The enzymatic degradation behavior of the LLStereo monolayers was surprised by the two-step kinetics as the area ratio, A/A0; it promptly decreased during an initial stage, which includes conformational stability and degradation of unstable complexed PLLA chains. However, the A/A0 behavior of HHStereo is very similar to that of HPDLA. The reason is that when the molecular weight exceeds a certain level, the stereocomplexed monolayers are stable for the enzyme due to a stereo effect.The majority of PLA degradation research was carried out using PLLA polymer, whereas, as per the author’s knowledge, only one report was reported using PDLA . The forn that is difficult to form clear films. Similar morphologies have been reported [reported ,38. Low-reported ,40,41,42sc in the PLLA/PDLA blends increased surprisingly, the highest Tsc was recorded at around 236 °C. The effect of the molecular weights of PLA on the enzymatic degradation behavior was studied at the molecular level with the Langmuir system. Homopolymer PLLA with a molecular weight of 10 k or less was degraded rapidly at the water/air interface, and the degradation rate was reduced significantly from 10 k or more. On account of confirming the degradation behavior by applying this to the stereocomplex, the degradation rate of a stereocomplex composed of a molecular weight of 10 k or less was delayed, but the degradation rate was still faster than that of the isomer PLA mixtures with a higher molecular weight. However, it was confirmed that when the molecular weight was greater than 15 k, degradation occurred rapidly at the beginning stage, but the degradation rate gradually decreased significantly. These results will expand the cognizance of PLA and PLA stereocomplex with different molecular weights, and superior thermal and degradation properties will contribute to more potential applications for PLA stereocomplex materials.In this study, PLA with different molecular weights was synthesized by the solution polymerization method to control molecular weight and chain architecture compared to conventional bulk polymerization. Results demonstrated that the molecular weights did not modulate the crystal structure of PLA and stereocomplexes, and the PLA stereocomplex was formed in all the blends. It has been confirmed through DSC analysis that stereocomplexation was thoroughly performed even at a molecular weight of 10 k or less. The melting temperatures in PLLA and PDLA increased uniformly as molecular weight increased. Although the T


The use of electroconvulsive therapy (ECT) as a treatment for psychotic disorders is well-documented and effective. Despite the fact that ECT is often used, the precise neurobiological mechanisms supporting its effectiveness are still incompletely understood. Over the pastyears, extensive research on primates, rodents, and humans has begun to clarify the effects of electroconvulsive seizures (ECS) and ECT on neurotransmission systems such the dopaminergic system.The aim of this paper is to search evidence in the literature regarding the effects of ECT on the dopamine system.In order to write this article, we searched for information in the most important scientific articles from the Google Scholar and Pubmed databases regarding the effects of ECT on the dopaminergic system.ECT and electroconvulsive shock are linked to enhanced dopamine release and dopamine receptor modification. Human studies show that ECT activates the dopamine system. In a study by Rudorfer et al., it was discovered that ECT increased the amount of homovanillic acid (HVA), a marker of dopamine turnover, in the cerebrospinal fluid (CRF). One important study indicates that monkeys given a brief clinical course of ECT (six sessions only) exhibit significant changes in dopaminergic presynaptic neurotransmission, with baseline function returning to quadratic (‘inverted U’ shape) by six weeks of the last ECT treatment. According to single-unit electrophysiological methods, repeated electroconvulsive shock to rats causes a subsensitivity of dopamine autoreceptors in the substantia nigra. Since effects identical to those reported with repeated treatment were also detected when a single electroconvulsive shock was followed by an acceptable treatment-free interval, this decreased sensitivity is time-dependent.The results support the idea that ECT boosts the dopamine system and can be an effective strategy in the management of psychotic disorders.None Declared


Topic modelling with innovative deep learning methods has gained interest for a wide range of applications that includes COVID-19. It can provide, psychological, social and cultural insights for understanding human behaviour in extreme events such as the COVID-19 pandemic. In this paper, we use prominent deep learning-based language models for COVID-19 topic modelling taking into account data from the emergence (Alpha) to the Omicron variant in India. Our results show that the topics extracted for the subsequent waves had certain overlapping themes such as governance, vaccination, and pandemic management while novel issues aroused in political, social and economic situations during the COVID-19 pandemic. We also find a strong correlation between the major topics with news media prevalent during the respective time period. Hence, our framework has the potential to capture major issues arising during different phases of the COVID-19 pandemic which can be extended to other countries and regions. World Health Organisation (WHO) first reported COVID-19 as a public health crisis in January 2020 and declared it a pandemic in March 2020 [The coronavirus pandemic COVID-19), also known as (SARS-CoV-2) 9, also k gave extrch 2020 . India rrch 2020 . India aMinistry of Health and Family Welfare and Government of India in collaboration with WHO to prevent and control the spread of the virus within and across states of India [During the first COVID-19 wave in India (March—October 2020), several measures were taken by Indian of India , sports of India . Despiteof India . During of India  of whichof India .Social media became one of the major platforms to spread information on COVID-19 ; with acTopic modelling is a domain in natural language processing (NLP) that is used to detect ‘topics’, analyse them, and classify them according to common patterns and themes emerging across the corpus , 24. It long short-term memory (LSTM) networks [bi-directional encoder representative from transformer (BERT) [Researchers have used deep learning models such as networks  and bi-dr (BERT)  models tr (BERT)  implemenr (BERT)  used a BIn this paper, we use a deep learning-based language framework for COVID-19 topic modelling taking into account data from COVID-19 emergence, which includes Alpha, Delta and Omicron variants for the three distinct peaks (waves) in India. We use Twitter data from India and also compare it with our earlier works that looked at sentiment analysis of the first wave in India. We note that we refer to the three distant peaks as waves and define their time frame in the methodology section. Our goal is to extract and study the various topics emerging in the three different waves and discuss the relationship to emerging events and issues in the media during the respective time frames. Our goal is to observe how the emerging events affected the topics covered in COVID-19 tweets during the respective time frames. The major contribution of our study is in the application of novel deep learning-based language models for topic modelling during COVID-19 based on Twitter data. We also compare our results with traditional topic models (such as LDA).The rest of the paper is organised as follows. In Section 2, we provide further details about the methodology which includes data processing and models. In Section 3, we present the results and highlight major observations. Section 4 provides a discussion about the results in relation to emerging events in the respective waves. Section 5 concludes the paper with directions for subsequent research.https://www.worldometers.info/coronavirus/). India recorded its second wave with a major and much higher peak of cases that spanned March to July 2021 [Although India had a prolonged first wave which lasted almost a year, it recorded lower COVID-19 prevalence in terms of the number of cases and deaths when compared to USA . India huly 2021 . In the uly 2021 . In compuly 2021 . The Deluly 2021  also emeuly 2021 . Afterwauly 2021 . The thiuly 2021 . The defuly 2021 .hydrator (https://github.com/DocNow/hydrator) to extract the tweets, which is a time-consuming process due to restrictions given by Twitter to ensure that the data is not misused. We also obtained the dataset of tweet handles (i.e. tweet identifier) for the second and third waves from IEEE Dataport- COV19Tweets [We obtained the dataset of tweets originating from India during the COVID-19 first wave from the IEEE Dataport  for Indi19Tweets , which f19Tweets .hydrator software application to extract the daily tweets worldwide and then separated the India-specific tweets from the global dataset. We have obtained 30,000 tweets per day from India for three selected days a week for the time frame of the second and third wave defined in terms and conditions of Twitter and the IEEE Dataport. We obtained hydrated tweets with the following identifiers with information as given below:We used the ‘coordinates’ represents the geographic location of the tweet as reported by the user or client application.‘created_at’ gives the UTC date and time that the user account was created on Twitter.‘hashtags’ represents hashtags that have been parsed out of the tweet.‘media’ represents a media object representing a single photo, video or animated GIF.‘urls’ gives web-link provided by the user in association with their profile.‘favourite_count’ provides the number of Tweets this user has liked in the account’s lifetime. Note that British spelling is used in the field name for historical reasons.‘id’ provides the integer representation of the unique identifier for a user.‘in_reply_to_screen_name’ contains the screen name of the original tweet’s author if the tweet is a reply.‘in_reply_to_status’ contains the integer representation of the original tweet’s ID if the tweet is a reply.‘lang’(language) provides language information.‘country_code’ represents the country.‘text’ gives name of the hashtag, minus the leading ‘#’ character‘retweet_count’ provides the number of times the tweet has been retweeted.‘user_description’ provides the user-defined UTF-8 string describing their account.‘user_favourite_counts’ provides the number of tweets the user has liked in the account’s lifetime.We pre-processed the entire dataset consisting of the three waves, which consists of the following steps.Removal of punctuation and web links (URLs);Removal of mentions in tweets;https://pypi.org/project/emoji2text/);Conversion of symbols used for emotions (emojis) into text using emoji2text .Lemmatisation process to group similar words using the natural language toolkit (NLTK) library  [The  (GSDMM)  works we (GSDMM) . Short t (GSDMM)  presente (GSDMM)  showed tT topic distributions, Randomly choose Randomly choose a distribution over topics, d = 1, 2, …, D:a) randomly choose a topic For each document, β are integrated out of the posterior distribution The collapsed Gibbs sampler was developed based on the following rationale. Whilst conditional distributions can be derived for all the variables since BERT is a pre-trained language model  which isBERTBASE which consists of 12 transformer blocks and a total of 110 million parameters, and BERTLARGE which consists of 24 transformer blocks with 340 million parameters. Although BERT is pre-trained, it is usually trained further with datasets for specific applications, such as sentiment analysis of COVID-19-related tweets during the rise of novel cases [BERT pre-training phase involves semi-supervised learning tasks such as masked language modelling , 59, 60 el cases , and senel cases .Hierarchical density-based spatial clustering of application with noise (HDBSCAN) [Clustering methods refer to unsupervised machine learning that groups unlabelled data based on a given similarity measure. The goal of clustering algorithms is to assign each data point a label or a cluster identity and several types of clustering algorithms exit with strengths and weaknesses given the type of data . HierarcHDBSCAN) , 64 defiHDBSCAN) –70. FurtHDBSCAN) . Top2Vecword is the basic unit of data which refers to items from the dataset (vocabulary) of size V indexed by {1, …, V}. A collection of words is known as a document which can be denoted as w = {w1, w2, …, wN} for a sequence of size N; where wi is the ith word. The collection of M documents is known as a corpus denoted by D = {w1, w2, …, wM} [In topic modelling, a , …, wM} .We present a framework to employ various machine learning models for topic modeling as shown in Figs Topic2Vec model. Note that LDA and GSDMM can be directly used for topic modelling and hence the final topics are directly obtained rather than using a word embedding method and clustering algorithm. The original BERT model is computationally intensive for making predictions. Sentence BERT (S-BERT) [BERTbase with HDBSCAN which is referred to as the BERT topic model (BERT-TM), hereon. We pass the word embeddings generated by S-BERT to the Top2Vec pipeline where the documents are placed close to other similar documents. Note that S-BERT is embedded within the Top2Vec model in order to obtain word embedding.In (S-BERT)  improveduniform manifold approximation and projection (UMAP) [Since our S-BERT-based word embedding model has a large vector of features, we need a dimensional reduction method to reduce the features. Hence, we use n (UMAP)  which isn (UMAP)  for visun (UMAP)  evaluateGensim [In Gensim , an openintruder which is a word with a very low probability of belonging to the given topic [topic coherence (TC) [normalized pointwise mutual information(NPMI) correlates really well with the human evaluation and interpretation of the topic coherence [A topic coherence measure is typically used to evaluate topic models in order to measure their ability to capture topics (i.e. low perplexity) and represent coherent semantic meaning. There are two different strategies for topic coherence measure: 1.) rating, where human evaluators rate the topic quality on a three-point topic quality score, and 2.) intrusion, where each topic is represented by the most frequent words along with an en topic . We use nce (TC)  as a metoherence . Röder eoherence  presentewi, wj), from the top N (set to 50) words of a given topic as given below:P(wi) by the Boolean sliding window approach . We create a virtual document and count the occurrence of the word (wi) and the word pairs , which is then divided by the total number of the virtual documents.Note that the NPMI is a step used in topic coherence measure for a pair of words  obtained from pretable . Apart fU and V is represented by We carry out further investigations using the BERT-TM which gave the best topic coherence results in the previous section. In order to evaluate the relationship between the first and the second wave of COVID-19, we use the topics obtained to find a similarity matrix and present a heatmap  to estabNext, we evaluate and discuss similar relationships both quantitatively using a mathematical formulation and also qualitatively by looking at the topics generated by our models as shown in phase one lockdown of 21 days  was estimated to be almost 98 billion dollars [Next, we review the topics with emerging events and reports from the media during the first wave of COVID-19. India observed a nationwide lockdown where the estimated economic cost of the  dollars . The firIndian Yoga Guru, Baba Ramdev made controversial comments about modern medicine and oxygen cylinders (May 2021) . He partIndia started to experience waves of recession with the coming of the first wave. Over 30% of all industrial goods in India are transported via trains. Therefore, railway freight volumes become an important indicator of economic activity in the country. We note that that many parts of India, including metro cities such as Mumbai and Delhi were under state government-imposed lockdowns. The daily average railway freight volumes in India dropped by 11% in April, according to Indian Railways data . One of We continue with our results from the previous section that compared the first and second waves. We can now compare the second and third waves of COVID-19 in India using the similarity matrix  where thNext, we discuss how the topics relate to the media coverage of the second wave of COVID-19 in India. The second and third waves in India had major overlapping topics over ‘vaccination’, ‘vaccines’, ‘vaccinework’ as shown in Given the possibility of a third wave, in November 2021 the Indian Army increased its medical capacity across the country, while also helping the civilian administration in tackling the coronavirus   inter-stIn India witnessed a number of major events during the three waves, which included several regional elections spanning 2020—2022 , farmersCovaxin with the age group-wise vaccine drive in India [Our results indicate that the major topics during the first wave feature lockdowns, economic crises, school closures, vaccines, government policies, the reaction of the people, death polls, donations, celebrities in India, doctors and hospitals, and religion. The second wave saw a rise in the number of topics related to vaccines such as in India . We founin India . We notein India  with a hin India . In the in India , the topin India .hydrator. Our team manually downloaded and checked the process at regular intervalsalong with segregation of monthly data as well as country-wise, this took more than six months of our time. However, we managed to publish the dataset (password protected to suit Twitter policy) in Kaggle [We note that a large effort was made in hydration of the dataset using the Twitter tool known as n Kaggle . Our datIn terms of limitations, we note that the data source considered was not taken daily, but taken on three selected days of the week. Moreover, it is difficult to apply topic modelling methods to tweets since they are restricted by size and also include everyday language expressions that rely on local regions and are also influenced by regional languages in India. Although the data is sourced in English, we note that most of India has English as a second language and there are a number of regional languages in India. The 2011 Indian census recorded 31 regional Indian languages  had at least one million speakers each ; this giIn this paper, we presented a topic modelling framework for COVID-19 topic modelling in India via Twitter. We first compared BERT-based topic modelling with conventional approaches and found that BERT-based topic modelling performs better in terms of topic coherence. Hence, we used it further to extract topics from the three major waves in India and reviewed the correlation of major topics between the different waves. We reported topics that were distinct for particular waves and also prominent throughout the pandemic. We found a strong correlation between some of the topics qualitatively to news media prevalent at the respective time-frames (waves). Our topic modelling framework provides a systematic methodology for understanding the major topics during COVID-19 in social media that cover governance, vaccination, management, and challenges that included lockdowns and the economy. The framework can be extended to other countries and events to study topics emerging in social media.


The surgery-first approach (SFA) is conducted to decrease the difficulty and duration of orthodontic treatment by correcting the skeletal discrepancy at the initial stage of treatment. However, the indication of the SFA has not been well defined yet. This study explored the dental occlusion characteristics for treatment decision-making regarding the SFA. A total of 200 skeletal Class III patients were consecutively collected and divided into two groups: the orthodontic-first approach (OFA) group and the SFA group. The pretreatment digital dental models and lateral cephalograms were measured. Logistic regression was completed and receiver operating characteristic (ROC) curves were obtained to predict the probability of the SFA. Results showed that the ROC model with L1-MP, upper and lower arch length discrepancy, overbite, and asymmetric tooth number as influencing factors revealed that the sensitivity and specificity for determining SFA were 83.0% and 65.0%, respectively; the accuracy of prediction was 75.0%. In conclusion, our findings indicate that the six measurements from digital dental models and lateral cephalograms can be effectively applied in treatment decision-making for the SFA with satisfactory accuracy. The conventional surgical–orthodontic treatment for patients with Class III deformities is typically performed as a three-stage approach: presurgical orthodontic treatment, orthognathic surgery, and postoperative treatment ,2,3. AltThe criteria for the SFA include the following parameters: alignment of dentition, inclination of anterior teeth, curve of Spee, and transverse discrepancy ,6,13,14.Factors related to skeletal discrepancy have also been proposed as indicators of whether the SFA should be employed. Hernández-Alfaro et al. recommended that patients who present severe facial asymmetry with dental compensation should be excluded from consideration for the SFA . HoweverThus, although the SFA was an aesthetic/skeletal-first concept, the factors determining patient selection for this approach have mainly been dental characteristics. The optimal surgical occlusion design for the surgery-first approach is a “treatable malocclusion” that does not interfere with surgical movement ,17. UnliAs a result, the evaluation of dental occlusion plays a crucial role in the selection of the Surgery First Approach (SFA) or the Orthodontic First Approach (OFA). Digital models offer several advantages over traditional plaster models, including cost-effectiveness, time efficiency, and storage convenience. Furthermore, digital models are highly reliable and exhibit exceptional accuracy, positioning them as the modern gold standard in orthodontic practice ,31. In tAt the Chang Gung Craniofacial Center in Taipei, Taiwan, the SFA has been consistently applied for an extended duration. The proficient surgeons have developed several refinements to surgical techniques, enabling them to effectively achieve sagittal, vertical, and transverse dental decompensation through segmental osteotomy, thereby broadening the indications for the SFA . MoreoveThis retrospective cohort study examined a series of consecutive patients who underwent surgical–orthodontic treatment. The inclusion criteria were (1) Taiwanese adult aged ≥20 years, (2) having skeletal Class III malocclusion with an ANB angle ≤ 0, (3) having undergone two-jaw surgery, (4) having ≤2 missing teeth per quadrant (third molars are not included), (5) having completed postsurgical orthodontic treatment, and (6) having pretreatment cephalometric radiographs and digital dental models. Patients with craniofacial anomalies, facial trauma history, and incomplete diagnostic records were excluded.This study included 200 patients who were divided into two groups according to their treatment modality: the OFA group  and the SFA group (39 men and 61 women who received orthognathic surgery before any orthodontic treatment). As the design in surgical occlusion necessitates careful consideration, the responsibility of selecting appropriate cases for SFA falls upon an experienced orthodontist. The selection of the OFA or SFA was based on the initial model manipulation and surgical occlusion management. The occlusion with interference and the inability to set up proper surgical occlusion were categorized into the OFA group. The clinical reasons for selecting the OFA were documented in clinical charts. This study was approved by the Institutional Review Board and Medical Ethics Committee of Chang Gung Memorial Hospital (IRB No. 201901921B0) and followed the guidelines of the Declaration of Helsinki.To create digital models, pretreatment plaster casts were scanned using an extraoral scanner , and the Standard Tessellation Language file was transferred to OrthoAnalyzer software (3Shape) for digital model analysis.The following three-dimensional planes were used to standardize the orientation and improve the accuracy of the dental model measurement: (1) the occlusal plane, passing through the mesiobuccal cusp of the bilateral first molars and the most extruded point on the incisal edge of the central incisors; (2) the midsagittal plane, passing through the center of the incisive papilla and midpalatine raphe, perpendicular to the occlusal plane; and (3) the coronal plane, separating the anterior and posterior regions and perpendicular to the occlusal plane and midsagittal plane .On the plane parallel to the midsagittal plane passing through the middle of the central incisors, the patients’ overbites and overjets were measured, and the average values were used.ALD was defined as the absolute space required minus the dental arch length, including UALD and LALD (upper and lower arches). The space required was calculated as the sum of the mesiodistal width of the premolars and anterior teeth. The dental arch length was measured using the ideal arch form on the virtual occlusal plane, in which a curved arch length was measured relative to the apical base.The transverse discrepancy included the ICW discrepancy and IMW discrepancy, in which the maxillary value minus the mandibular value was obtained.The difference in the distance between the midsagittal plane and the bilateral cusp tip of the canines, premolars, and molars was measured. The square root of the squared sum of the three numbers was calculated as the AI to generate an absolute number.The tooth number from the central incisor to the first molar was recorded bilaterally. It was then categorized into dichotomized variables as “same” or “different”.The depth of the curve of Spee was measured as the perpendicular distance between the deepest cusp tip to the plane touching the incisal edges of the central incisors and the distal cusp tips of the first molar in the lower arch. The average value was recorded .Cephalometric measurements were obtained using digital lateral cephalograms in Centricity Enterprise , and the incisor inclination of the maxilla (SN-U1) and mandible (MP-L1) was measured .t-test. Logistic regression analyses were performed to identify the predictors of candidacy for the SFA. Backward stepwise multiple logistic regression was applied to develop a prediction sequence for the variables. Receiver operator characteristic (ROC) analysis was performed to identify the cutoff point of each variable to determine its distinguishing ability. The scoring system was developed according to the cutoff points and prediction ability sequence. Cumulative ranked scores were analyzed with ROC curves and univariate logistic regression to determine the final prediction ability and accuracy of the model by comparing the estimated results with actual observations. All statistical analyses were conducted using SPSS v22.0 .Between-group differences were compared using the independent t-test was used for systematic errors. The interclass correlation coefficient (ICC) test was used to test reproducibility.All measurements were conducted by a single examiner (Y.C.C.). Ten digital casts were randomly selected to conduct a reexamination after an interval of 2 weeks. The validation of measurement consistency was assessed. A paired t-test results indicated no significant difference between the two sets of measurements. The ICC test indicated excellent measurement reproducibility (0.96–0.99).For the demographic characteristics, this study included 100 patients in the SFA group  and 100 patients in the OFA group . The sex and age distributions were not significantly different between the two groups. The mean period of presurgical orthodontic treatment was 6.9 months, during which alignment, leveling, partial incisor inclination correction, and anterior arch coordination were performed, depending on the objective of the case . The ANBBased on dental model manipulation for the surgical occlusion setup, the necessity of presurgical orthodontic treatment was determined for each patient. The indicators for selecting the OFA are listed in p < 0.05). The upper incisor inclination did not significantly differ between the two groups (p > 0.05). However, compared with the SFA group, the OFA group exhibited more severe crowding and spacing in both the upper and lower arches and significantly deeper overbite and curve of Spee . For the arch form and tooth number symmetry, the OFA group exhibited a greater AI and a higher prevalence of asymmetric tooth number in bilateral arch than the SFA group did (p < 0.05) (The OFA group exhibited more upright lower incisor inclination than the SFA group did ( < 0.05) .To develop a scoring system, this study first used the ROC curves to determine cutoff points by using the maximum sum of the sensitivity and specificity for each variable . The parThe study employed logistic regression to establish the order of variables by predictability, with UALD, OB, MP-L1, LALD, ATN, SN-U1, curve of Spee, OJ, AI, IMW, and ICW in descending order. Scores were cumulatively aggregated following this sequence. The dichotomized scoring system showed a larger AUC than the original parameters, enhancing discriminative power. The study aimed for an effective diagnostic model by identifying the most accurate scoring system instead of using all variables. It found that a six-variable system  had the highest AUC (0.8) and diagnostic accuracy (75%) . Each vaWith advancements in digital dentistry, the use of digital dental models for orthodontic analysis is becoming increasingly popular. Compared with those of plaster models, the reproducibility and repeatability of the measurements of digital models were compatible ,33. In tGiven that the establishment of surgical occlusion as a treatable malocclusion in SFA is a prerequisite, the responsibility of selecting appropriate cases for SFA falls upon an experienced orthodontist. Additionally, the orthodontist not only formulates the surgical plan but also collaborates with surgeons to incorporate any necessary modifications. This underscores the orthodontist’s comprehensive understanding of the interplay between surgical occlusion and the intended surgical movements. It is important to note, however, that different specialists might approach the selection process differently. For instance, some more seasoned orthodontists may designate all patients as potential candidates for SFA. Nonetheless, achieving predictable outcomes demands a higher degree of surgical technique and experience. In this study, while the cases are divided into two categorical groups for selection purposes, they are ultimately integrated into a scoring system. This scoring system would be invaluable for orthodontists and surgeons alike, irrespective of orthognathic teams’ levels of experience and institutes.t-test. An independent t-test compares only differences in mean values; on the other hand, the curve of receiver operating characteristic could reveal the grouping probability. This scoring model shows high sensitivity which indicates that it can more precisely select patients for the SFA. The medium level of specificity of the prediction model can be compensated through modification: in borderline cases, that is, cases with a score of 4 points, consideration of other parameters, such as dental transverse discrepancy, curve of Spee, asymmetric arch form, or directly surgical occlusion manipulation might be applied for selection of treatment modalities.To the best of our knowledge, this study is the first to quantify the occlusion characteristics of patients with Class III malocclusion and to evaluate the probability of variables being candidates for the SFA by using ROC curves. Patients with a score of more than 4 points on our six-variable scoring system are likely to be candidates for the SFA, with a prediction accuracy of 75%. Five of the six variables  were significantly different between the two study groups. Although SN-U1 is not, the prediction ability, including the sensitivity and specificity of the factor, is measured using the ROC curve rather than the independent Our previous study compared occlusion parameters by using digital occlusal analysis (T-Scan) on patients for whom the SFA and OFA were applied. Sharing the same case selection philosophy as this study, the results of the study indicated that all occlusion parameters, including force discrepancy, occlusal time, maximum forced percentage, and number of teeth in contact, after surgery were similar in the SFA and OFA groups . The stuSkeletal Class III patients are typically associated with maxillary deficiency and therefore present with upper dental crowding and labially proclined upper incisors ,37. The For correction of upper incisor inclination or compensation, there are several treatment options. For the severe upper incisor proclination, upper premolar extraction followed by anterior teeth retraction is common in the OFA group for decompensation ,29. In aThe results of this study show that patients with shallow overbites (OB ≤ 2 mm) and retroclined lower incisor angles (MP-L1 ≤ 76.1°) had a higher tendency to undergo the SFA. These characteristics typically show more in Class III high mandibular plane angle patients. Uribe et al. indicates that Class III malocclusion with anterior open bite usually has mild crowding and less dental compensation; thus, they are good candidates for SFA . In otheThe small number of patients with facial asymmetry indicates that asymmetric arch form is not a determining factor for candidacy for the OFA. The asymmetric arch form might be due to dental compensation in facial asymmetry. The side shift of mandibular surgical movement is restricted by the palatal inclination of the maxillary arch on the non-deviated side. In patients with severe dental compensation, presurgical arch expansion through posterior teeth decompensation and increasing upper intercanine width (ICW) can aid in the surgical occlusion setup, enabling a wider range of mandibular side shifting during the surgical correction of facial asymmetry. Moreover, for cases presenting Class I occlusion with a complete palatal crossbite in hand articulation, presurgical decompensation can be considered to prevent postsurgical interference. Conversely, maxillary basal bone asymmetry can be addressed through segmental osteotomy to expand the dental arch in cases of skeletal facial asymmetry in SFA. ICW and IMW were the least decisive factors according to the scoring system. Previous studies reported that the ICW of Class III was similar to that of patients with Class I malocclusion, and the IMW of Class III was smaller than Class I subjects ,43. HoweBased on the results of the study, all the presurgical orthodontic treatments were aimed at (1) eliminating major dental interference, (2) consolidating dental space and the coordinate dental midline within the arch, (3) facilitating major arch form alteration by preparing space and solving future problems for segmental osteotomies, and (4) enhancing surgical stability if major closing movement of mandible is predicted such as a deep curve of Spee in skeletal Class III deformities. On the other hand, presurgical orthodontic treatment should not aim for full dental decompensation and full arch coordination with a lengthy period of presurgical orthodontics. Only a short period of orthodontic treatment of about six months, eliminating the main interference for surgical occlusion setup, can be achieved. Other than the aforementioned conditions, SFA can be conducted with applaudable and stable outcomes. According to the result of this study, the scoring system can be a screening tool for decision making of the surgical–orthodontic treatment modalities: SFA or OFA, especially for beginners in SFA. The study was retrospectively designed, a setup that tends to introduce more limitations to the findings. In order to mitigate this bias, it would be contemplating the possibility of devising a multicenter prospective randomized trial in the future.Patients who require presurgical orthodontic treatment tend to have more upright lower incisor inclination, more crowded or spaced dentition in both arches, a deep curve of Spee and overbite, and an asymmetric arch form in Class III surgical orthodontics.For optimal discriminant effectiveness between SFA and OFA, six variables were selected to predict the probability of SFA candidacy with an accuracy of 75%, including UALD ≤ 4.1 mm, OB ≤ 2.0 mm, MP-L1 ≤ 76.1 mm, LALD ≤ 1.4 mm, no ATN, and SN-U1 ≤ 120.8°.In the scoring system, a score of 4 provided a favorable prediction of the probability of SFA candidacy, with a sensitivity of 83% and specificity of 67%.In borderline cases with a score of 4 points, other parameters such as dental arch transverse discrepancy, asymmetric arch form, curve of Spee, or computed surgical simulation may be considered for the decision of treatment modalities.The scoring system could simplify the decision-making procedure for SFA and OFA.