Nations' ongoing struggles with a number of novel and reemerging infectious diseases, including the ongoing global health issue, the SARS-Co-V2 (severe acute respiratory syndrome coronavirus 2) ...outbreak, serve as proof that infectious diseases constitute a serious threat to the global public health. Moreover, the fatality rate in humans is rising as a result of the development of severe infectious diseases brought about by multiple drug-tolerant pathogenic microorganisms. The widespread use of traditional antimicrobial drugs, immunosuppressive medications, and other related factors led to the establishment of such drug resistant pathogenic microbial species. To overcome the difficulties commonly encountered by current infectious disease management and control processes, like inadequate effectiveness, toxicities, and the evolution of drug tolerance, new treatment solutions are required. Fortunately, immunotherapies already hold great potential for reducing these restrictions while simultaneously expanding the boundaries of healthcare and medicine, as shown by the latest discoveries and the success of drugs including monoclonal antibodies (MAbs), vaccinations, etc. Immunotherapies comprise methods for treating diseases that specifically target or affect the body's immune system and such immunological procedures/therapies strengthen the host's defenses to fight those infections. The immunotherapy-based treatments control the host's innate and adaptive immune responses, which are effective in treating different pathogenic microbial infections. As a result, diverse immunotherapeutic strategies are being researched more and more as alternative treatments for infectious diseases, leading to substantial improvements in our comprehension of the associations between pathogens and host immune system. In this review we will explore different immunotherapies and their usage for the assistance of a broad spectrum of infectious ailments caused by various human bacterial and fungal pathogenic microbes. We will discuss about the recent developments in the therapeutics against the growing human pathogenic microbial diseases and focus on the present and future of using immunotherapies to overcome these diseases. Graphical AbstractThe graphical abstract shows the therapeutic potential of different types of immunotherapies like vaccines, monoclonal antibodies-based therapies, etc., against different kinds of human Bacterial and Fungal microbial infections.
The incidence of human fungal infections is increasing due to the expansion of the immunocompromised patient population. The continuous use of different antifungal agents has eventually resulted in ...the establishment of resistant fungal species. The fungal pathogens unfold multiple resistance strategies to successfully tackle the effect of different antifungal agents. For the successful colonization and establishment of infection inside the host, the pathogenic fungi switch to the process of metabolic flexibility to regulate distinct nutrient uptake systems as well as to modulate their metabolism accordingly. Glucose the most favourable carbon source helps carry out the important survival and niche colonization processes. Adopting glucose as the center, this review has been put forward to provide an outline of the important processes like growth, the progression of infection, and the metabolism regulated by glucose, affecting the pathogenicity and virulence traits in the human pathogenic fungi. This could help in the identification of better treatment options and appropriate target-oriented antifungal drugs based on the glucose-regulated pathways and processes. In the article, we have also presented a summary of the novel studies and findings pointing to glucose-based potential therapeutic avenues to be explored to tackle the problem of globally increasing multidrug-resistant human fungal infections.
•QDR MFS transporters serve as one of the causes of pathogenicity and virulence.•QDRKO strains show differential expression of genes like glucose transporters.•These strains show higher intracellular ...glucose and glycerol accumulation levels.•Enhanced hyphal forms and elevated azole drug resistance was also observed.•Exploring such pathways can give novel insights into disease pathogenesis.
ATP-binding cassette (ABC) and Major Facilitator Superfamily (MFS) transporters have been known to play an important role in the development of multidrug resistance (MDR) in various fungal species. While the importance of ABC transporters in MDR development is widely understood, MFS exporters have gotten little attention. The role of QDR (quinidine drug resistance) transporters (CaQDR1, CaQDR2, and CaQDR3), a subfamily of MFS, in conferring pathogenicity and virulence to Candida albicans is highlighted in this study. The transcriptome analysis of QDR knockout (QDRKO) strains versus wild-type (WT) strains of C. albicans reveals differential expression of some important virulence-associated gene categories. These include chitin and β-glucan synthases, mannosyl transferases, vacuolar, ion transporters, acid phosphatase, and different sugar transporter (HGT8 and HGT9) encoding genes. Although some of the related phenotypic assays could not show any considerable differences in the growth of knockout strains under relevant stresses, however, we discovered elevated expression levels of different HGT genes in QDRKO strains, particularly under glucose limiting conditions as evidenced by the higher intracellular glucose accumulation levels. All the strains (QDRKOs and WT) followed a similar pattern in the accumulation of metabolite glycerol. Interestingly, QDRKO strains exhibit an enhanced azole drug resistance than the parental Candida strain, particularly at a low glucose concentration of the culture media. Our findings imply that deleting QDR genes (individually or collectively) alters cellular pathways, particularly those associated with glucose and glycerol accumulation. This possibly provides the cells with a mechanism to overcome stress and partially maintain the cellular pathogenicity/virulence in the absence of QDR MFS transporters.
Crystal engineering is one green alternative to organic synthesis that can be used to manipulate molecular behavior promptly and economically. We report the preparation and characterization of the ...pharmaceutical organic salt (FLC-C) of fluconazole (FLC) and organosulfonate (NDSA-2H), based on the sulfonate-pyridinium supramolecular synthon. Structural studies validate the crystallization of the two-component stoichiometric crystal with two molecules of water in the triclinic P1̅ space group. The anticipated proton transfer between the crystal forms leads to ionic interactions, augmenting the organic salt’s thermal stability. Hirshfeld studies of FLC-C help to understand the role and significance of different types of intermolecular interactions responsible for crystal packing. The structural and theoretical studies indicate the absence of π–π interactions in FLC-C, which account for the incipience of solid-state emission in the product. The solubility studies establish augmented aqueous solubility of FLC-C over pristine FLC at physiological pH values of 2 and 7. Interestingly, in in vitro studies, FLC-C appears to serve as a potential alternative to FLC, displaying a wide spectrum of antifungal activity. FLC-C is active against several human pathogenic yeast strains, including the leading and emerging Candida strains (Candida albicans and Candida auris, respectively), at comparable and/or lower drug concentrations without showing any enhanced host cell toxicity. Interestingly, the pharmaceutical co-crystal also displays fluorescence properties inside the Candida cells.
Objective: To find out the echo abnormalities in a south Asian cohort on maintenance hemodialysis in a tertiary care hospital.
Study Design: Descriptive cross-sectional study.
Place and Duration of ...Study: Combined Military Hospital Abbottabad, from Feb 2022 to Apr 2022.
Methodology: 57 adult patients on maintenance hemodialysis had a non-contrast transthoracic echocardiographic study recording parameters of left and right ventricular systolic and diastolic function.
Results: We had 57 patients. 71.9% (n=41) were male, and females 28.1% (n=16), diabetics 47.4 % (n=27), hypertensives 84.2%(n=48), smoking 28.1% (n=16); 15.8%(n=9) had some form of ischemic heart disease. Left ventricular hypertrophy was noted in 78.9% (n=45) of the entire patient population. 84% (n=48) of hypertensive patients had LVH. Overall, 82% (n=47) of hypertensive patients had some degree of diastolic dysfunction compared to non-hypertensive patients (p<0.0001). Diastolic dysfunction of Grades I, II, III was seen in 35.1%(n=20), 29.8%(n=17), 17.5% (n=10). Mean E/e' ratio was 24.9±15, with 40.3%(n=23) having a value ≥15. The LV systolic dysfunction noted was: Mild 26.3%(n=15), Moderate 19.3%(n=11), Severe 1.8%(n=1). For the medial mitral annular systolic velocity(s’) 19.3%(n=11) had normal s’, while 80.7%(n=46) had reduced s’.The mean Pulmonary artery acceleration time (PA-AT) was was <100 ms in 68.4%(n=39). The mean tricuspid plane systolic excursion (TAPSE) was < 17 mm in 19.3%(n=11) of patients indicating RV systolic dysfunction. The Minimum PASP was 16, max 64, mean 41.5±14mm Hg.
Conclusion: In our study of CKD patients on regular hemodialysis, we found high rates of LVH, DD, LV systolic dysfunction,RV systolic function, and pulmonary hypertension. This creates a case for a larger scale study of these patients in a south Asian cohort as well as institution of a screening program in CKD patients on hemodialysis.
Objective: To detect residual RV dysfunction on a right ventricle focused Transthoracic Echocardiography (TTE) in COVID-19 infection survivors with lung involvement.
Study Design: Analytical Cross ...sectional study design.
Place and Duration of Study: Combined Military Hospital Abbottabad Pakistan, Feb 2022 to Apr 2022.
Methodology: 87 patients who had suffered from and survived COVID-19 infection with definite involvement on CT scans of the chest were studied after discharge. Echocardiography was done to determine the RV anatomical and functional parameters to determine the relationship between extent of lung involvement and transthoracic echocardiographic parameters.Data was entered in Microsoft excel and exported to SPSS v 23 for analysis.
Results: The initial sample size was of 87 patients. Due to suboptimal ECHO studies 7 cases were excluded. Males represented 62.5% (n=50) and females 37.5% (n=30). The ages ranged from 27 to 80 years, mean 53.08±12.77 years. Based on the CT severity score severe infections were 61.3 %(n=49) and mild 38.8% (n=31). The CTSS ranged from 6 to 30 with a mean of (17.74±7.13). In our study we found that on TTE, there was a statistically significant difference in 2 of the anatomical parameters; RVOT PLAX (RVOT diameter in Parasternal long axis view) 27.4 vs 28.3; p=0.02, RVOT-Dis (Distal RVOT dia) 22.8 vs 24; p=0.01. In addition, there was a statistically significant difference in all the functional parameters of RV function TDI S vel (Systolic Tissue Doppler Velocity of the Tricuspid Annulus by Tissue doppler imaging) 7 vs4.9; p<0.0001, RIMPPW (Right Ventricular Index of Myocardial Performance by Pulse wave doppler) 0.46 vs0.38; p<0.0001, RIMP-TDI (Right Ventricular Index of Myocardial Performance by Tissue doppler imaging) 0.57 vs 0.48; p<0.0001. RV-FAC (RV-Fractional Area Change) was statistically insignificant. 42.8% vs 43.2%; p=0.6.
Conclusion: Our study showed that in patients with definite lung involvement on chest CT scans, functional echocardiographic parameters of Right ventricular function were affected in line with the severity of lung involvement.
Cardiac surgery was severely affected by the COVID‐19 pandemic. Reallocation of resources, conversion of surgical intensive care units and wards to COVID‐19 facilities, increased risk of nosocomial ...transmission to cardiac surgery patients, lead to reduced accessibility, quality, and affordability of health care facilities to cardiac surgery patients. Increasing the mortality and morbidity rate among such patients. Cardiac patients are at an increased risk to develop a severe illness if infected by COVID‐19 and are associated with a high mortality rate. Therefore, measures had to be taken to reduce the spread of the virus. Various approaches such as the hubs and the spokes centers, or parallel system were enforced. Elective surgeries were postponed while urgent surgeries were prioritized. Use of personal protective equipments and surgeries performed by only senior surgeons became necessary. Surgical trainees were also affected as limited training opportunities deprived them of the experience required to complete their fellowship. Some of the trainees were reallocated to COVID‐19 wards, while others invested their time in research opportunities. Online platforms were used for teaching, meetings, and workshops across the globe. Although some efforts have been made to reduce the impact of the pandemic, more research and innovation is required.
PurposeCOVID-19 infection resulting from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began to spread across the globe in early 2020. Patients with hematologic malignancies are ...supposed to have an increased risk of mortality from coronavirus disease of 2019 (COVID-19) infection. From Pakistan, we report the analysis of the outcome and interaction between patient demographics and tumor subtype and COVID-19 infection and hematological malignancy.Patients and methodsThis multicenter, retrospective study included adult patients with a history of histologically proven hematological malignancies who were tested positive for COVID-19 via PCR presented at the oncology department of 5 tertiary care hospitals in Pakistan from February to August 2020. A patient with any known hematological malignancy who was positive for COVID-19 on RT-PCR, was included in the study. Chi-square test and Cox-regression hazard regression model was applied considering p ≤ 0.05 significant.ResultsA total of 107 patients with hematological malignancies were diagnosed with COVID-19, out of which 82 (76.64%) were alive, and 25 (23.36%) were dead. The significant hematological malignancy was B-cell Lymphoma in dead 4 (16.00%) and alive group 21 (25.61%), respectively. The majority of the patients in both the dead and alive group were on active treatment for hematological malignancy while they came positive for COVID-19 21 (84.00%) & 48 (58.54%) p 0.020. All patients in the dead group were admitted to the hospital 25 (100.00%), and among these, 14 (56.00%) were admitted in ICU with a median 11 (6-16.5) number of days. Among those who had contact exposure, the hazard of survival or death in patients with hematological malignancies and COVID-19 positive was 2.18 (CI: 1.90-4.44) times and 3.10 (CI: 2.73-4.60) times in patients with travel history compared to no exposure history (p 0.001).ConclusionTaken together, this data supports the emerging consensus that patients with hematologic malignancies experience significant morbidity and mortality resulting from COVID-19 infection.
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