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OBJECTIVE: Immunosuppression and microbial resistance are the major drawbacks in conventional pharmaceutics. The present research work was planned to screen and characterize phytochemical constituents present in Phyllanthus emblica and to explore the immunomodulation potential of P. emblica by evaluating stress markers and different biochemical parameters in animals. MATERIALS AND METHODS: The phytochemical analysis explored the presence of antioxidant profiles and revealed the radical scavenging activities. In the second phase, an animal trial was performed using female albino rats. Female rats (n=18) were administered three different doses of P. emblica (low dose 100 mg/kg, intermediate 200 mg/kg, and high dose 300 mg/kg) for three weeks. After a significant change (p<0.05) in antioxidant status i.e., TOS and TAS, hematological, biochemical parameters, and immunoregulation i.e., IgM and IgG were elevated. Statistical analysis (ANOVA) illustrates that these selected plants have a great impact on microbial resistance and immunosuppression and have shown highly significant results. RESULTS: The results of all in vitro and in vivo assays conducted as part of the recent research work offer considerable evidence that the chosen medicinal plant has the ability to induce specific hormone release and boost the immune system. CONCLUSIONS: Based on our findings, it is proposed that medicinal herbs may be isolated using cutting-edge approaches to tackle the issues of immunosuppression and microbial resistance. [ABSTRACT FROM AUTHOR]

Silver nanoparticles have special plasmonic and antibacterial characteristics that make them efficient in a variety of commercial medical applications. According to recent research, chemically synthesized silver nanoparticles are harmful even in low concentrations. It was crucial to identify appropriate synthesis methods that may have low costs and be nontoxic to the environment. Zingiber officinale (ginger) extracts used to prepare silver nanoparticles were inexpensive and environmentally friendly, and the best physicochemical characteristics were analyzed. Silver nanoparticles were characterized by using UV-visible spectroscopy, Scanning electron microscopy (SEM), and X-ray diffraction (XRD). The surface Plasmon resonance peak at 425 nm was observed using UV-Visible spectroscopy. Scanning electron microscopy observed that the nanoparticles were spherical and ranged in size from 5 to 35 nm. The XRD pattern values of 2θ: 38.2o, 46.3o, and 64.58o are used to determine the planes (111), (200), and (220). The silver nanoparticle’s existence was verified by the face-centered cubic (FCC). Silver nanoparticles were found to have antibacterial efficacy against gram-positive Staphylococcus and gram-negative bacteria such as Pseudomonas aeruginosa, Klebsiella Aerogenes, Salmonella, Staphylococcus and Escherichia coli. The antibacterial activity of silver nanoparticles was observed using the agar well diffusion (AWD) method at three different concentrations (100 μg/ml, 75 μg/ml, and 50 μg/ml). The zone of inhibition measured against the bacterial strains pseudomonas Aeruginosa, Klebsiella aerogenes, Escherichia coli, Salmonella and Staphylococcus which were (18.4±1.25 mm, 16.9±0.74 mm, 14.8±1.25 mm), (16.8±0.96 mm, 14.6±0.76 mm, 14.0±1.15 mm), (19.7±0.76 mm, 18.2±0.66 mm, 15.4±1.15 mm), (16.6±0.67 mm, 14.2±0.23 mm, 12.8±0.78 mm) and (12±0.68 mm, 10±0.20 mm, 08±0.15 mm). These nanoparticles’ potent antibacterial properties may enable them to be employed as nanomedicines for a variety of gram-negative bacterial illness treatments.

Abstract A subset of patients with metastatic renal cell carcinoma (mRCC) follow an indolent disease course and may benefit from initial active surveillance (AS). However, selecting patients suitable for this approach is challenging. To investigate this we sought to define outcomes of patients with mRCC suitable for initial AS. All patients with mRCC clinically selected for initial AS at the Edinburgh Cancer Centre between January 2010 and December 2020 were identified. Key inflammatory biomarkers (haemoglobin, white cell count, neutrophil count, platelets, C‐reactive protein [CRP], albumin, corrected calcium) and the International Metastatic RCC Database Consortium (IMDC) risk score were measured. The relationship between these and time to systemic anticancer therapy (tSACT) and overall survival (OS) was analysed. Data were available for 160 patients. Estimated median overall survival was 88.0 (interquartile range [IQR] 34.0–127.0) months. Median tSACT was 31.8 (IQR 12.0–76.3) months. On multivariate analysis, only CRP was predictive of tSACT (HR 2.47 [95% CI:1.59–3.85] p 10 mg/L were more likely to commence SACT within 1 year than those with CRP≤10 mg/L (41% vs. 18%, Relative Risk 2.16 (95% CI:1.18–3.96) (p = 0.012)). IMDC risk score was not predictive of tSACT or OS. Active surveillance is an appropriate initial management option for selected patients with mRCC. CRP, a biomarker of systemic inflammation, may provide additional objective information to assist clinical decision‐making in patients with mRCC being considered for initial AS. Although this is a retrospective observational study, the cohort is well defined and includes all patients managed with initial AS in an inclusive real‐world setting.

Starting from the end of 2019 the new SARs-CoV-2 virus, in the period of a few months, had spread to 210 countries and its territories. The Wuhan wild animal market, in Hubei province, China is considered the epicenter of this pandemic. WHO declared the name COVID-19 to designate the disease caused by the SARS-CoV-2 virus. It is the third coronavirus pandemic after SARS in 2002–2003 and MERS-CoV in 2012. Genome sequencing of this new COVID-19/SARS-CoV-2 virus shows slight genetic diversity when compared to other coronaviruses. Owing to its pathogenesis, and less known replication cycle, no universal antiviral treatment can be applied and vaccine preparation is still a larger challenge. The present article will highlight transmission, pandemic status, genetic diversity current antiviral therapy, and vaccine trials for COVID-19.

Objective: To evaluate the diagnostic efficacy of laparoscopy in ill-defined recurrent chronic abdominal pain. Study Design: Prospective study. Place and Duration of Study: Surgical department, Military Hospital Rawalpindi, from Jul 2011 to Dec 2013. Material and Methods: A total of 102 patients who presented to surgical department with chronic recurrent abdominal pain of unknown etiology and underwent diagnostic laparoscopy were included in our study. Patients with acute onset of abdominal pain, hemodynamically unstable, pregnant or those in which diagnosis can be made by radiological techniques were excluded from our study. Patient’s demographic data, clinical findings and laparoscopic findings were recorded. Finally data was analyzed by using SPSS version 21. Results: Out of 110 patients 96 were female while remaining 14 were male. The age range of the patients was 20- 70 years with mean age of 50 ± 10 years. The most common site of pain was lower abdomen while mean duration of abdominal pain was 34 weeks. Laparoscopic findings include acute recurrent appendicitis in 32 (29.09%) patients, cholecystitis with biliary sludge in 14 (12.72%), pelvic inflammatory disease in 12 (10.90%), ovarian cyst in 11(10%), adhesions in 10(9.09%), intestinal tuberculosis in 8 (7.27%), mesenteric lymphadenitis in 7 (6.36%), lymphoma in 4 (3.63%), ectopic pregnancy in 3 (2.7%), CA gallbladder in 2 (1.81%), meckels diverticulum in 2 (1.81%), endometriosis in 2 (1.81%) and crohns disease in 1 (0.9%) patients. Mean operative time was 48 min while average hospital stay was 2-3 days. No major complications were noticed. Conclusion: Laparoscopy in our clinical setup has significant role in diagnosing cases of vague abdominal pain which cannot be diagnosed by routine investigations. [ABSTRACT FROM AUTHOR]

Objective: To determine the etiological spectrum of perforation peritonitis in patients undergoing laparotomy at Military Hospital Rawalpindi. Study Design: Descriptive Study. Place and Duration of Study: Surgical department, Military Hospital, Rawalpindi from Jun 2011 to Jan 2014, over a period of about 2.5 year. Material and Methods: A total of 150 patients with perforation peritonitis who underwent laparotomy were included in our study while those in which peritonitis was result of complication of previous treatment such as anastomotic dehiscence were excluded from the study. All the patients were selected by consecutive sampling technique. Patients' demographic data, pre-op data, operative findings and post-op data were recorded and finally analyzed by using SPSS version 21. Results: Out of 150 patients 128 were females while remaining 22 were males, with male to female ratio of 1:5.81. Age range of patients was 20-70 with mean age of 30 ± 10. Major presenting complaints were acute abdomen, vomiting, abdominal distension, fever and altered bowel habits. Seven percent patients gave positive history of use of NSAIDs. Operative findings include typhoid in 33 (22%), tuberculosis in 25 (16.6%), duodenal ulcer perforation in 22 (14.6%), appendicitis in 20 (13.3%), traumatic perforation in 18(12%), malignancy in 16 (10.6%), strangulation of bowel in 6(4%), gastric ulcer in 5 (3.3%), volvulus in 3(2%), Meckels diverticulum in 1(0.6%) and CMV(Cytomegalovirus) ileal perforation in 1(0.6%) patients. Small bowel was the most common site of perforation. Post-op complications include wound infection, fever, wound dehiscence, burst abdomen, anastomosis leak, sepsis and cardiac and respiratory complications. Conclusion: Enteric fever is the commonest cause of perforation peritonitis in our setup followed by intestinal tuberculosis as the second most common cause. Small bowel is the most common site of perforation. [ABSTRACT FROM AUTHOR]

Testicular cancer is the most common malignancy in young adult men. The prognosis is excellent in limited disease and cure is possible even in advanced disease. Quality performance indicators (QPI) are used in many developed countries as a measure of healthcare performance. We report and discuss the development of a national set of QPIs in Scotland for testicular cancer as a method of gathering demographic data and driving improvement in nationwide testicular cancer outcomes.

The current study focuses on the submerged fermentation of tyrosine hydroxylase (TH) from Aspergillus oryzae IIB-9 and its immobilization on zinc oxide nanocrystals (ZnO-NPs) for increased L-dopa production. The volume of Vogel's medium (75 ml), period of incubation (72 h), initial pH (5.5), and size of inoculum (1.5 ml) were optimal for maximum TH activity. The watch glass-dried (WG) and filter paper-dried (FP) ZnO-NPs were prepared and characterized using analytical techniques. The UV-Vis spectra revealed 295 and 285 nm absorption peaks for WG-ZnO-NPs and FP-ZnO-NPs dispersed in isopropanol. X-ray diffraction analysis confirmed the crystalline nature of ZnO-NPs. FTIR spectra band from 740 to 648.1/cm and 735.8/cm to 650.1/cm showed the stretching vibrations of WG-ZnO-NPs and FP-ZnO-NPs, respectively. The particle size of ZnO-NPs observed by scanning electron microscopy (SEM) images was between 130 and 170 nm. Furthermore, the stability of immobilized TH on ZnO-NPs was determined by varying the incubation period (10 min for WG-NPs and 15 min for FP-NPs) and temperature (45 °C and 30 °C for WG and FP-NPs, respectively). Incubating enzymes with various copper, iron, manganese, and zinc salts studied the catalytic efficiency of TH. Immobilization of TH on ZnO-NPs resulted in an 11.05-fold increase in TH activity, thus enhancing stability and catalytic efficiency., (© 2023. The Author(s).)

Infertility is a well-recognized multifactorial problem affecting the majority of people who struggle with infertility issues. In recent times, among infertility cases, the male factor has acquired importance, and now it contributes to approximately half of the infertility cases because of different abnormalities. In the current study, we used natural phytochemicals as potential drug-lead compounds to target different receptor proteins that are involved in the onset of male infertility. A set of 210 plant phytochemicals were docked counter to active site residues of sex hormone-binding globulin, a disintegrin and metalloproteinase 17, and DNase I as receptor proteins. On the basis of binding scores and molecular dynamics simulation, the phytochemicals tricin, quercetin, malvidin, rhamnetin, isorhamnetin, gallic acid, kaempferol, esculin, robinetin, and okanin were found to be the potential drug candidates to treat male infertility. Molecular dynamics simulation showed tricin as a strong inhibitor of all selected receptor proteins because the ligand-protein complexes remained stabilized during the entire simulation time of 100 ns. Further, an in vivo study was designed to evaluate the effect of tricin in male rats with nicotine-induced infertility. It was explored that a high dose of tricin significantly reduced the levels of alanine transaminase, aspartate transaminase, urea, creatinine, cholesterol, triglyceride, and low-density lipoprotein and raised the level of high-density lipoprotein in intoxicated male rats. A high dose of tricin also increased the reproductive hormones (i.e., testosterone, luteinizing hormone, follicle-stimulating hormone, and prolactin) and reduced the level of DHEA-SO4. The phytochemical (tricin, 10 mg/kg body weight) also showed significant improvement in the histo-architecture after nicotine intoxication in rats. From the current study, it is concluded that the phytochemical tricin could serve as a potential drug candidate to cure male infertility.

Gastric ulcer is the most prevalent disorder affecting a large population. Rosa brunonii Lindl. fruit (RBF) has traditionally been used to treat stomach pains. Therefore, the current work aimed to isolate, characterize, and investigate the gastro-protective effect of Rosa brunonii Lindl. fruit chloroform extract (RBFCE) against ethanol-induced gastric ulcers in rats. Quercetin 3-O-glucoside (QUE-G) was isolated and characterized by modern spectroscopic techniques. RBFCE was orally administered at 250 mg/kg, 500 mg/kg, and 750 mg/kg doses for ten days. Gastric ulcer was induced by a single dose of absolute ethanol (5 ml/kg) on the last day of the study. Histological changes were calculated, along with ulcer inhibition and the ulcer index (UI). Gastric juice volume, pH, acidity, mucus content, and protein content were evaluated to understand the mechanism underlying its gastroprotective effect. Omeprazole (OMP) was used as the positive control. RBFCE at a dose of 750 mg/kg significantly (p<0.01) reduced the UI (3.54) and increased the protection rate (67.63%) compared to the negative (ulcer) control group. Treatment with RBFCE in a dose-dependent manner increased the gastric pH, mucus content, and total protein while decreasing gastric juice volume and total acidity. Histopathological studies showed severe gastric mucosal injury and edema in ulcer control animals compared to extract-treated groups. This study demonstrated that oral administration of RBFCE possesses a significant gastroprotective effect due to its anti-secretory and cytoprotective mechanisms. Our findings support the traditional use of RBF to treat the gastric ulcer.

Polysaccharides are biobased polymers obtained from renewable sources. They exhibit various interesting features including biocompatibility, biodegradability, and nontoxicity. Microbial polysaccharides are produced by several microorganisms including yeast, fungi, algae, and bacteria. Microbial polysaccharides have gained high importance in biotechnology due to their novel physiochemical characteristics and composition. Among microbial polysaccharides, xanthan, alginate, gellan, and dextran are the most commonly reported polysaccharides for the development of biomimetic materials for biomedical applications including targeted drug delivery, wound healing, and tissue engineering. Several chemical and physical cross-linking reactions are performed to increase their technological and functional properties. Owning to the broad-scale applications of microbial polysaccharides, this review aims to summarize the characteristics with different ways of physical/chemical crosslinking for polysaccharide regulation. Recently, several biopolymers have gained high importance due to their biologically active properties. This will help in the formation of bioactive nutraceuticals and functional foods. This review provides a perspective on microbial polysaccharides, with special emphasis given to applications in promising biosectors and the subsequent advancement on the discovery and development of new polysaccharides for adding new products., (© 2022 Wiley-VCH GmbH.)

Background: Natural medicines are being used for the treatment of various disorders due to pharmacological, therapeutical, and nutraceuticals characteristics., Objectives: Current research was planned to explore In vitro pharmacological response of phytochemical constituents extracted from C. monnieri' seeds using aqueous ethanol (70%)., Methods: Qualitative and quantitative measurements for phytochemical constituents were performed following reference protocols. Then In vitro antioxidant potential, cytotoxic studies, antimicrobial, and spermicidal pharmacological response of C. monnieri extract were investigated., Results: The results of High Performance Liquid Chromatography (HPLC), Fourier Transform Infra-Red (FTIR) spectroscopy, and Atomic Absorption Spectrophotometer (AAS) explored the presence of wide range of bioactive compounds with significant (p<.05) antioxidant activities. Cytotoxic studies revealed significant (p<.05) protective behavior of C. monnieri evaluated using CtDNA damage protection, against Salmonella typhi TA98 and TA100, RBCs membrane stabilizing and clot lysis assay. It was also found that selected herb has antibacterial and antifungal activities. The results of spermicidal study on human (n = 30) spermatozoa revealed significant (p<.05) contraceptive per vaginal behavior of this natural medicinal plant., Conclusion: It could be concluded that C. monnieri showed significant pharmacological activities with non-toxic behavior, however In vivo study in animals and clinical trials are required to declare this natural herb as therapeutic agent., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

The absence of novel and efficient methods for the elimination of persistent organic pollutants (POPs) from the environment is a serious concern in the society. The pollutants release into the atmosphere by means of industrialization and urbanization is a massive global hazard. Although, the eco-toxicity associated with nanotechnology is still being debated, nano-remediation is a potentially developing tool for dealing with contamination of the environment, particularly POPs. Nano-remediation is a novel strategy to the safe and long-term removal of POPs. This detailed review article presents an important perspective on latest innovations and future views of nano-remediation methods used for environmental decontamination, like nano-photocatalysis and nanosensing. Different kinds of nanomaterials including nanoscale zero-valent iron (nZVI), carbon nanotubes (CNTs), magnetic and metallic nanoparticles, silica (SiO 2 ) nanoparticles, graphene oxide, covalent organic frameworks (COFs), and metal organic frameworks (MOFs) have been summarized for the mitigation of POPs. Furthermore, the long-term viability of nano-remediation strategies for dealing with legacy contamination was considered, with a particular emphasis on environmental and health implications. The assessment goes on to discuss the environmental consequences of nanotechnology and offers consensual recommendations on how to employ nanotechnology for a greater present and a more prosperous future., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Parkinson's disease is a neurodegenerative disease caused by the death of neurons, ie, cells critical to the production of dopamine, an important neurotransmitter in the brain. Here, we present a brief review of the dopamine synthetic pathway, binding to the dopamine receptors, and subsequent action. The production of dopamine (a monoamine neurotransmitter) occurs in the ventral tegmental area (VTA) of the substantia nigra, specifically in the hypothalamic nucleus and midbrain. Compared to other monoamines, dopamine is widely distributed in the olfactory bulb, midbrain substantia nigra, hypothalamus, VTA, retina, and the periaqueductal gray area. Dopamine receptors are large G-protein coupled receptor family members, of which there are five subtypes including D1, D2, D3, D4, and D5. These subtypes are further divided into two subclasses: D1-like family receptors (types 1 and 5) and D2-like family receptors (types 2, 3, and 4). Four different pathways and functions of the dopaminergic system are presented in this review. In the oxidation of dopamine, 5,6-indolequinone, dopamine-o-quinone, and aminochrome are formed. It is difficult to separate the roles of 5,6-indolequinone and dopamine-o-quinone in the degenerative process of Parkinson's diseases due to their instability. The role of aminochrome in Parkinson's disease is to form and stabilize the neurotoxic protofibrils of alpha-synuclein, mitochondrial dysfunction, oxidative stress, and the degradation of protein by lysosomal systems and proteasomes. The neurotoxic effects of aminochrome can be inhibited by preventing the polymerization of 5,6-indolequinone, dopamine-o-quinone, and aminochrome into neuromelanin, by reducing aminochrome catalysis by DT-diaphorase, and by preventing dopamine oxidative deamination catalyzed by monoamine oxidase. In addition to these, the conversion of dopamine in the neuromelanin (NM) shows both protective and toxic roles. Therefore, the aims of this review were to discuss and explain the role of dopamine and explore its physiology and specificity in Parkinson's disease, as well as its role in other physiological functions., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Human papillomavirus (HPV) is a well-known sexually transmitted disorder globally. Human papillomavirus (HPV) is the 3rd most common cancer that causes cervical carcinoma, and globally it accounts for 275,000 deaths every year. The load of HPV-associated abrasions can be lessened through vaccination. At present, three forms of prophylactic vaccines, Cervarix, Gadrasil, and Gardasil 9, are commercially accessible but all these prophylactic vaccines have not the ability to manage and control developed abrasions or infections. Therefore, a considerable amount of the population is not secured from HPV infectivity. Consequently, the development of therapeutic HPV vaccines is a crucial requirement of this era, for the treatment of persisting infections, and to stop the progression of HPV-associated cancers. Therapeutic vaccines are a developing trial approach. Because of the constitutive expression of E6 and E7 early genes in cancerous and pre-cancerous tissues, and their involvement in disturbance of the cell cycle, these are best targets for this therapeutic vaccine treatment. For the synthesis and development of therapeutic vaccines, various approaches have been examined comprising cell-based vaccines, peptide/protein-based vaccines, nucleic acid-based vaccines, and live-vector vaccines all proceeding towards clinical trials. This review emphasizes the development, progress, current status, and future perspective of several vaccines for the cure of HPV-related abrasions and cancers. This review also provides an insight to assess the effectiveness, safety, efficacy, and immunogenicity of therapeutic vaccines in the cure of patients infected with HPV-associated cervical cancer., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Hantaviruses are enveloped negative (-) single-stranded RNA viruses belongs to Hantaviridae family, hosted by small rodents and entering into the human body through inhalation, causing haemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) also known as hantavirus cardiopulmonary syndrome (HCPS). Hantaviruses infect approximately more than 200 000 people annually all around the world and its mortality rate is about 35%-40%. Hantaviruses play significant role in affecting the target cells as these inhibit the apoptotic factor in these cells. These viruses impair the integrity of endothelial barrier due to an excessive innate immune response that is proposed to be central in the pathogenesis and is a hallmark of hantavirus disease. A wide range of different diagnostic tools including polymerase chain reaction (PCR), focus reduction neutralization test (FRNT), enzyme-linked immunosorbent assay (ELISA), immunoblot assay (IBA), immunofluorescence assay (IFA), and other molecular techniques are used as detection tools for hantavirus in the human body. Now the availability of therapeutic modalities is the major challenge to control this deadly virus because still no FDA approved drug or vaccine is available. Antiviral agents, DNA-based vaccines, polyclonal and monoclonal antibodies neutralized the viruses so these techniques are considered as the hope for the treatment of hantavirus disease. This review has been compiled to provide a comprehensive overview of hantaviruses disease, its pathophysiology, diagnostic tools and the treatment approaches to control the hantavirus infection., (© 2020 John Wiley & Sons Australia, Ltd.)

Hepatitis C virus (HCV) is a primary cause of chronic liver disease along with various complications like liver cirrhosis and malignancy which leads to death. It has infected more than 185 million people worldwide. There is no congruence established for the treatment of various genotypes of HCV infection owing to diversity in prevalence globally. Assessment of affected individuals with HCV by polymerase chain reaction (PCR), viral load of HCV and liver enzyme levels (i.e., ALT and AST) are the foundation to evaluate the safety and efficacy of HCV therapies. The antiviral efficacy has been greatly improved and sustained viral response (SVR) rates increased from 6% with interferon monotherapy to 50-80% with PEG-interferon/ribavirin combination therapy to >95% after the approval of all interferon free oral direct acting antiviral agents. The main objective of this review article is to compile data from reference sources regarding the old and current therapeutic strategies used to manage HCV infection. It is accepted that chronic HCV infection increases patient's thrombocytopenia and neutropenia risk and complications increased in co-morbid disorders like in tuberculosis, HIV, diabetes etc. In past treatment associated side effects were the major consequences and many patients have to stop the treatment. But after the approval of direct acting antiviral drugs create a revolution in the treatment of HCV infection. So, it could be concluded that current combination therapies are a promising hope to eradicate and to control HCV but some safety concerns required more considerations Therefore, this review focus on the available latest combination therapies and their effectiveness to eradicate HCV infection.

Naegleria fowleri, a thermophilic flagellate amoeba known as a "brain-eating" amoeba, is the aetiological agent of a perilous and devastating waterborne disease known as primary amoebic meningoencephalitis (PAM), both in humans as well as in animals. PAM is a rare but fatal disease affecting young adults all around the world, particularly in the developed world but recently reported from developing countries, with 95%-99% mortality rate. Swimmers and divers are at high risk of PAM as the warm water is the most propitious environment adapted by N. fowleri to cause this infection. Infective amoeba in the trophozoite phase enter the victim's body through the nose, crossing the cribriform plate to reach the human brain and cause severe destruction of the central nervous system (CNS). The brain damage leads to brain haemorrhage and death occurs within 3-7 days in undiagnosed cases and maltreated cases. Though the exact pathogenesis of N. fowleri is still not known, it has exhibited two primary mechanisms, contact-independent (brain damage through different proteins) and contact-dependent (brain damage through surface structures food cups), that predominantly contribute to the pathogen invading the host CNS. For the management of this life-threatening infection different treatment regimens have been applied but still the survival rate is only 5% which is ascribed to its misdiagnosis, as the PAM symptoms closely resembled bacterial meningitis. The main objectives of this review article are to compile data to explore the sources and routes of N. fowleri infection, its association in causing PAM along with its pathophysiology; latest techniques used for accurate diagnosis, management options along with challenges for Pakistan to control this drastic disorder., (© 2019 John Wiley & Sons Australia, Ltd.)