Monitoring the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) immunization in patients with autoimmune diseases is of particular concern to understand their response to the infection and to the vaccine. In fact, the immunological disorder and the immunosuppressive therapies could affect the serological response. SARS-CoV2 serological tests potentially provide this information, although they were rapidly commercialized with internal verifications. Here, we analysed the seroprevalence to SARS-CoV2 in a cohort of patients with liver autoimmune diseases.
From May to December 2020, a cohort of patients affected by primary biliary cholangitis (PBC), autoimmune hepatitis (AIH) and PBC/AIH overlap syndrome were screened with reverse transcription-polymerase chain reaction (RT-PCR) of nasopharyngeal swabs, rapid antigenic test and chemiluminescent serological test during routine follow-up.
The analysis of 42 patients was carried out: 18 (42.85%) PBC, 12 (28.57%) AIH and 12 (28.57%) PBC/AIH overlap syndromes. Only 2 patients (4.76%) resulted positive to the RNA, antigen and antibody detection tests, hence affected by SARS-CoV2 infection. 14 subjects out of 40 negative cases presented a positive serology for SARS-CoV2 antibodies, hence with a false positivity in the 35% of cases without infection. Notably, among these, 6 (42.86%) patients presented only immunoglobulin (Ig)M positivity, 6 (42.86%) patients presented positivity for only IgG and 2 (14.28%) patients were positive to both IgM and IgG. Notably, the presence of autoantibodies did not correlate with the serological false positivity, highlighting that there is no cross-reactivity with autoantibodies. Moreover, the presence of polyclonal hypergammaglobulinemia did not interfere with the serological test as its prevalence is not different between negative and false positive cases. Interestingly, the patients with false positive serology showed higher levels of gamma-glutamyltransferase (GGT) and C-reactive protein (CRP).
Patients with liver autoimmune diseases present a high rate of false positive SARS-CoV2 serology. Therefore, new strategies are needed to study the serological response in this patient category.
Monitoring the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) immunization in patients with autoimmune diseases is of particular concern to understand their response to the infection and to the vaccine. In fact, the immunological disorder and the immunosuppressive therapies could affect the serological response. SARS-CoV2 serological tests potentially provide this information, although they were rapidly commercialized with internal verifications. Here, we analysed the seroprevalence to SARS-CoV2 in a cohort of patients with liver autoimmune diseases.
From May to December 2020, a cohort of patients affected by primary biliary cholangitis (PBC), autoimmune hepatitis (AIH) and PBC/AIH overlap syndrome were screened with reverse transcription-polymerase chain reaction (RT-PCR) of nasopharyngeal swabs, rapid antigenic test and chemiluminescent serological test during routine follow-up.
The analysis of 42 patients was carried out: 18 (42.85%) PBC, 12 (28.57%) AIH and 12 (28.57%) PBC/AIH overlap syndromes. Only 2 patients (4.76%) resulted positive to the RNA, antigen and antibody detection tests, hence affected by SARS-CoV2 infection. 14 subjects out of 40 negative cases presented a positive serology for SARS-CoV2 antibodies, hence with a false positivity in the 35% of cases without infection. Notably, among these, 6 (42.86%) patients presented only immunoglobulin (Ig)M positivity, 6 (42.86%) patients presented positivity for only IgG and 2 (14.28%) patients were positive to both IgM and IgG. Notably, the presence of autoantibodies did not correlate with the serological false positivity, highlighting that there is no cross-reactivity with autoantibodies. Moreover, the presence of polyclonal hypergammaglobulinemia did not interfere with the serological test as its prevalence is not different between negative and false positive cases. Interestingly, the patients with false positive serology showed higher levels of gamma-glutamyltransferase (GGT) and C-reactive protein (CRP).
Patients with liver autoimmune diseases present a high rate of false positive SARS-CoV2 serology. Therefore, new strategies are needed to study the serological response in this patient category.
The high heterogeneity in the definitions of low back pain encountered in the literature has led to the development of standardized definitions of this condition called “Delphi definitions of low back pain prevalence (Delphi DOLBaPP)” by a group of international researchers. In order to be widely used, these definitions need to be adapted according to the cultural and linguistic context. The aim of this work was to perform the cross-cultural adaptation of the Delphi DOLBaPP definitions in Quebec French and to pre-test them among French-speaking adults.
In order to enable practical use of the Delphi DOLBaPP definitions in different contexts, their presentation was adapted in the form of a questionnaire (referred to as the “Delphi DOLBaPP questionnaire”). The process of cross-cultural adaptation of the Delphi DOLBaPP questionnaire in French was conducted according to the most recognized recommendations for the cultural adaptation of measuring instruments. The resulting questionnaire and an evaluation form were then submitted to a sample of 82 adults.
A total of 41 participants (50.0%) reported low back pain. A high proportion of participants (89.0%) stated that it took them less than 5 minutes to complete the questionnaire. More than 62.0% of them did not find any question poorly worded or confusing. Nearly 80.0% of the participants found the questionnaire easy to understand. The cross-cultural adaptation process suggested minor modifications to the original Delphi DOLBaPP questionnaire.
This study has produced a cross-cultural adaptation of the Delphi DOLBaPP questionnaire in Quebec French that will enable French-speaking populations to share the benefits of using standardized definitions of low back pain in epidemiological studies.
The high heterogeneity in the definitions of low back pain encountered in the literature has led to the development of standardized definitions of this condition called “Delphi definitions of low back pain prevalence (Delphi DOLBaPP)” by a group of international researchers. In order to be widely used, these definitions need to be adapted according to the cultural and linguistic context. The aim of this work was to perform the cross-cultural adaptation of the Delphi DOLBaPP definitions in Quebec French and to pre-test them among French-speaking adults.
In order to enable practical use of the Delphi DOLBaPP definitions in different contexts, their presentation was adapted in the form of a questionnaire (referred to as the “Delphi DOLBaPP questionnaire”). The process of cross-cultural adaptation of the Delphi DOLBaPP questionnaire in French was conducted according to the most recognized recommendations for the cultural adaptation of measuring instruments. The resulting questionnaire and an evaluation form were then submitted to a sample of 82 adults.
A total of 41 participants (50.0%) reported low back pain. A high proportion of participants (89.0%) stated that it took them less than 5 minutes to complete the questionnaire. More than 62.0% of them did not find any question poorly worded or confusing. Nearly 80.0% of the participants found the questionnaire easy to understand. The cross-cultural adaptation process suggested minor modifications to the original Delphi DOLBaPP questionnaire.
This study has produced a cross-cultural adaptation of the Delphi DOLBaPP questionnaire in Quebec French that will enable French-speaking populations to share the benefits of using standardized definitions of low back pain in epidemiological studies.
Nutraceuticals are organic and traditional foods consumed nowadays to maintain a healthy lifestyle and get rid of lifestyle diseases like obesity, cancer, diabetes, hypertension, etc. Globally, herbal products have become increasingly popular in recent years. Wheatgrass (Triticum aestivum) is a nutraceutical proven to be a dietary supplement and beneficial for cancer-suffering patients. Wheatgrass possesses many beneficial antioxidant properties: anti-cancer activity, anti-bacterial activity, anti-fungal activity, and anti-microbial activity. Due to the presence of resistant starch, lignans, phenolic acids, alkylresorcinols, and numerous antioxidant components, including carotenoids and tocopherols, this herbal plant is deserving attention as a source of dietary fiber. Patients consume wheatgrass during cancer treatment as an adjunct to reduce toxicity associated with drugs and chemotherapy and ultimately improve long-term outcomes. Studies have proved that wheatgrass helps treat pancreatic cancer, lung cancer, and breast cancer. So, the multi-targeted herbal drug—wheatgrass—is used as an adjunct therapy alongside conventional medicine to treat cancer and other diseases. A promising therapeutic nutraceutical for avoiding lifestyle disorders is wheatgrass.
Nutraceuticals are organic and traditional foods consumed nowadays to maintain a healthy lifestyle and get rid of lifestyle diseases like obesity, cancer, diabetes, hypertension, etc. Globally, herbal products have become increasingly popular in recent years. Wheatgrass (Triticum aestivum) is a nutraceutical proven to be a dietary supplement and beneficial for cancer-suffering patients. Wheatgrass possesses many beneficial antioxidant properties: anti-cancer activity, anti-bacterial activity, anti-fungal activity, and anti-microbial activity. Due to the presence of resistant starch, lignans, phenolic acids, alkylresorcinols, and numerous antioxidant components, including carotenoids and tocopherols, this herbal plant is deserving attention as a source of dietary fiber. Patients consume wheatgrass during cancer treatment as an adjunct to reduce toxicity associated with drugs and chemotherapy and ultimately improve long-term outcomes. Studies have proved that wheatgrass helps treat pancreatic cancer, lung cancer, and breast cancer. So, the multi-targeted herbal drug—wheatgrass—is used as an adjunct therapy alongside conventional medicine to treat cancer and other diseases. A promising therapeutic nutraceutical for avoiding lifestyle disorders is wheatgrass.
Given the male infertility’s pluri-etiological nature, thorough examinations are needed for its evaluation. Fructose and citric acid are simple biomolecules, easy to assay, which provide reliable information on the seminal vesicles and prostate, respectively. This study aimed to compare the seminal fructose and citric acid levels in men undergoing fertility evaluation and determine the relation between these markers and sperm parameters.
A prospective cross-sectional study was conducted on consenting male participants. Following 2010 seminal fluid analysis (SFA) manual of World Health Organization (WHO), semen samples were analyzed for several sperm parameters, seminal fructose and citric acid. Statistical analyses were performed using IBM SPSS 24.0 software. Significant statistical difference was considered at P < 0.05.
There is no significant difference between seminal fructose and citric acid levels amongst men with normal and abnormal sperm parameters as median seminal fructose and citric acid levels were 11.1 (7.4–17.1) mg/mL and 11.4 (7.3–15.2) mg/mL respectively (P ≥ 0.05). However, a high level of fructose was observed in the two groups according to the reference value. The study revealed a significant positive correlation between seminal fructose levels and semen volume (coefficient rho = 0.663; P = 0.001) and between seminal citric acid levels and semen volume (coefficient rho = 0.319; P = 0.004).
These biomarkers secretions can serve as markers of the state of their respective secreting glands and hence play a vital role in the investigation of male infertility.
Given the male infertility’s pluri-etiological nature, thorough examinations are needed for its evaluation. Fructose and citric acid are simple biomolecules, easy to assay, which provide reliable information on the seminal vesicles and prostate, respectively. This study aimed to compare the seminal fructose and citric acid levels in men undergoing fertility evaluation and determine the relation between these markers and sperm parameters.
A prospective cross-sectional study was conducted on consenting male participants. Following 2010 seminal fluid analysis (SFA) manual of World Health Organization (WHO), semen samples were analyzed for several sperm parameters, seminal fructose and citric acid. Statistical analyses were performed using IBM SPSS 24.0 software. Significant statistical difference was considered at P < 0.05.
There is no significant difference between seminal fructose and citric acid levels amongst men with normal and abnormal sperm parameters as median seminal fructose and citric acid levels were 11.1 (7.4–17.1) mg/mL and 11.4 (7.3–15.2) mg/mL respectively (P ≥ 0.05). However, a high level of fructose was observed in the two groups according to the reference value. The study revealed a significant positive correlation between seminal fructose levels and semen volume (coefficient rho = 0.663; P = 0.001) and between seminal citric acid levels and semen volume (coefficient rho = 0.319; P = 0.004).
These biomarkers secretions can serve as markers of the state of their respective secreting glands and hence play a vital role in the investigation of male infertility.
Wound healing is a complex phenomenon with various biological changes in tissue integrity, low-level laser therapy (LLLT) has acquired several unique components to help into accelerating tissue reconstruction and eventually wound healing. Thus, in the present systematic review and meta-analysis study, the role of LLLT in oral mucosal wound healing following surgical interventions was investigated.
The study databases, including PubMed, Web of Knowledge, Google Scholar, Scopus, and Cochrane, were searched by two blinded investigators considering eligible studies based on the following keywords: “Wound Healing”, “Oral Mucosal Wound Healing”, “Laser therapy”, “Low-level laser therapy”, “Oral Surgery”, “Photobiomodulation therapy”, among 88 screened, only 12 articles were eligible for the final analysis.
There was a significant difference between control and laser group in all mentioned studies in the case of wound epithelialization in gingiva, with weighted mean difference (MD) of –0.28, [95% confidence interval (CI): –0.37, –0.19, P < 0.001], periodontium 1 day postoperative, with weighted MD of –0.56 (95% CI: –0.84, –0.27, P < 0.001) and 7 days postoperative, with weighted MD of –0.73 (95% CI: –0.97, –0.49, P < 0.001). In the cases of postoperative pain, LLLT has significantly declined pain in comparison with control group with weighted MD of –0.47 (95% CI: –0.69, –0.24, P < 0.001) for 7 days postoperative and –0.55 (95% CI: –0.96, –0.13, P = 0.005) 14 days postoperatively.
LLLT can be used as a promising tool in oral surgeries because of its inevitable capability in accelerating wound healing and reducing intraoperative pain.
Wound healing is a complex phenomenon with various biological changes in tissue integrity, low-level laser therapy (LLLT) has acquired several unique components to help into accelerating tissue reconstruction and eventually wound healing. Thus, in the present systematic review and meta-analysis study, the role of LLLT in oral mucosal wound healing following surgical interventions was investigated.
The study databases, including PubMed, Web of Knowledge, Google Scholar, Scopus, and Cochrane, were searched by two blinded investigators considering eligible studies based on the following keywords: “Wound Healing”, “Oral Mucosal Wound Healing”, “Laser therapy”, “Low-level laser therapy”, “Oral Surgery”, “Photobiomodulation therapy”, among 88 screened, only 12 articles were eligible for the final analysis.
There was a significant difference between control and laser group in all mentioned studies in the case of wound epithelialization in gingiva, with weighted mean difference (MD) of –0.28, [95% confidence interval (CI): –0.37, –0.19, P < 0.001], periodontium 1 day postoperative, with weighted MD of –0.56 (95% CI: –0.84, –0.27, P < 0.001) and 7 days postoperative, with weighted MD of –0.73 (95% CI: –0.97, –0.49, P < 0.001). In the cases of postoperative pain, LLLT has significantly declined pain in comparison with control group with weighted MD of –0.47 (95% CI: –0.69, –0.24, P < 0.001) for 7 days postoperative and –0.55 (95% CI: –0.96, –0.13, P = 0.005) 14 days postoperatively.
LLLT can be used as a promising tool in oral surgeries because of its inevitable capability in accelerating wound healing and reducing intraoperative pain.
Current evidence on benefits of night-time blood pressure (BP) lowering drug treatment on cardiovascular disease (CVD) prevention attributable to the Ambulatory Blood Pressure Monitoring in the Prediction of Cardiovascular Events and Effects of Chronotherapy (MAPEC) trial and Bedtime hypertension treatment improves cardiovascular risk reduction (Hygia) trials has raised concern on their validity and methodology. In this commentary, the authors have updated the progress of the ongoing trials that were planned to examine the effect of night-time BP lowering drug treatment on CVD prevention. As compared to MAPEC and Hygia trials, three pragmatic trials the Blood Pressure Medication Timing (BPMedtime) trial (US), the Treatment In Morning versus Evening (TIME) trial (UK), Bedmed and Bedmed-frail (Canada) were planned without ambulatory BP monitoring. The BPMedtime trial was stopped after the pilot phase due to underestimated sample size and insufficient funds. TIME trial (UK) had a similar issue when changing the sample size from 10,269 to more than 20,000 participants. The TIME trial was completed and the initial results showing that protection against heart attack, stroke and vascular death is not affected by whether antihypertensive medications are taken in the morning or evening. The full study of the TIME trial is published in December 2022. Bedmed and Bedmed-frail trials are ongoing and will be completed in 2023. Time of taking BP lowering drug should be determined by patients at their convenience to improve the adherence. There was no difference in adverse effects of taking BP lowering drugs at night or morning. Evidence on the effect of night-time treatment on CVD events is inconsistent. The results from ongoing trials in Canada will contribute evidence to the use of BP lowering drug treatment for the prevention of CVD.
Current evidence on benefits of night-time blood pressure (BP) lowering drug treatment on cardiovascular disease (CVD) prevention attributable to the Ambulatory Blood Pressure Monitoring in the Prediction of Cardiovascular Events and Effects of Chronotherapy (MAPEC) trial and Bedtime hypertension treatment improves cardiovascular risk reduction (Hygia) trials has raised concern on their validity and methodology. In this commentary, the authors have updated the progress of the ongoing trials that were planned to examine the effect of night-time BP lowering drug treatment on CVD prevention. As compared to MAPEC and Hygia trials, three pragmatic trials the Blood Pressure Medication Timing (BPMedtime) trial (US), the Treatment In Morning versus Evening (TIME) trial (UK), Bedmed and Bedmed-frail (Canada) were planned without ambulatory BP monitoring. The BPMedtime trial was stopped after the pilot phase due to underestimated sample size and insufficient funds. TIME trial (UK) had a similar issue when changing the sample size from 10,269 to more than 20,000 participants. The TIME trial was completed and the initial results showing that protection against heart attack, stroke and vascular death is not affected by whether antihypertensive medications are taken in the morning or evening. The full study of the TIME trial is published in December 2022. Bedmed and Bedmed-frail trials are ongoing and will be completed in 2023. Time of taking BP lowering drug should be determined by patients at their convenience to improve the adherence. There was no difference in adverse effects of taking BP lowering drugs at night or morning. Evidence on the effect of night-time treatment on CVD events is inconsistent. The results from ongoing trials in Canada will contribute evidence to the use of BP lowering drug treatment for the prevention of CVD.
Inflammatory bowel disease (IBD) is a multifactorial chronic disease. Patients with IBD have an increased risk of developing colorectal cancer which has become a major health concern. IBD might exert a role of engrams for making the condition of specific inflammation in the gut. Dysregulation of immune cells induced by the command of engrams might be crucial in the pathogenesis of damages in gut epithelium. The anti-proliferative (APRO) family of anti-proliferative proteins characterized by immediate early responsive gene-products that might be involved in the machinery of the carcinogenesis in IBD. Herein, it is suggested that some probiotics with specific bacteria could prevent the development and/or progression of the IBD related tumors. In addition, consideration regarding the application of studying APRO family proteins for the comprehension of IBD related tumors has been presented. It is hypothesized that overexpression of Tob1, a member of APRO family proteins, in the epithelium of IBD could suppress the function of adjacent cytotoxic immune cells possibly via the paracrine signaling.
Inflammatory bowel disease (IBD) is a multifactorial chronic disease. Patients with IBD have an increased risk of developing colorectal cancer which has become a major health concern. IBD might exert a role of engrams for making the condition of specific inflammation in the gut. Dysregulation of immune cells induced by the command of engrams might be crucial in the pathogenesis of damages in gut epithelium. The anti-proliferative (APRO) family of anti-proliferative proteins characterized by immediate early responsive gene-products that might be involved in the machinery of the carcinogenesis in IBD. Herein, it is suggested that some probiotics with specific bacteria could prevent the development and/or progression of the IBD related tumors. In addition, consideration regarding the application of studying APRO family proteins for the comprehension of IBD related tumors has been presented. It is hypothesized that overexpression of Tob1, a member of APRO family proteins, in the epithelium of IBD could suppress the function of adjacent cytotoxic immune cells possibly via the paracrine signaling.
Acquired immunodeficiency syndrome (AIDS) is a global disease caused by human immunodeficiency virus (HIV). About 50 million people have died worldwide due to HIV-1 infection alone. HIV is a primary sexually transmitted infection but can also spread via breastfeeding, blood transfer, organ transfer, etc. Early detection with the maintenance of the disease is the only way to reduce the spread and severity of the disease. There are many conventional techniques for the detection of the virus. Still, recently nano-based diagnostic method remains a little ahead of these techniques due to advancements in nanotechnology. Nanomaterial-based biosensors constitute a significant part of the discussion because of their high sensitivity and accuracy. Nanobiosensors like electronic nano biosensors, quantum dot (QD)-based biosensors, optical biosensors, electronic biosensors, electrochemiluminescence nanosensors, field-effect transistor (FET) biosensors, surface acoustic wave (SAW) biosensors, graphene-based biosensors, etc. have been widely used for detecting HIV in human blood samples. All these biosensors offer promising results in the detection of the virus. In this article, different types of nanobiosensors and their application in the field of diagnosis and maintenance of HIV was reviewed.
Acquired immunodeficiency syndrome (AIDS) is a global disease caused by human immunodeficiency virus (HIV). About 50 million people have died worldwide due to HIV-1 infection alone. HIV is a primary sexually transmitted infection but can also spread via breastfeeding, blood transfer, organ transfer, etc. Early detection with the maintenance of the disease is the only way to reduce the spread and severity of the disease. There are many conventional techniques for the detection of the virus. Still, recently nano-based diagnostic method remains a little ahead of these techniques due to advancements in nanotechnology. Nanomaterial-based biosensors constitute a significant part of the discussion because of their high sensitivity and accuracy. Nanobiosensors like electronic nano biosensors, quantum dot (QD)-based biosensors, optical biosensors, electronic biosensors, electrochemiluminescence nanosensors, field-effect transistor (FET) biosensors, surface acoustic wave (SAW) biosensors, graphene-based biosensors, etc. have been widely used for detecting HIV in human blood samples. All these biosensors offer promising results in the detection of the virus. In this article, different types of nanobiosensors and their application in the field of diagnosis and maintenance of HIV was reviewed.
Mitochondria are important organelles for high energy synthesis, reactive oxygen species balancing, antiapoptotic molecule production, membrane stability, intracellular calcium buffering, neuroplasticity and neurotransmission. Dysfunction in mitochondria is considered to be involved in the pathophysiology of mental problems. It has been observed that several drug types used to treat brain illnesses can harm mitochondria by altering the oxidative phosphorylation system and the gene expression of mitochondria-related proteins. In some studies, it has been observed that mitochondrial biogenesis shows a therapeutic effect in the management of mitochondrial disorders. Many therapeutic compounds are effective in the activation of mitochondrial biogenesis. The comorbidity of mental problems observed in those with mitochondrial dysfunction and the change in the efficacy of the cellular respiratory system have attracted researchers to understand the pathways and possible therapeutic strategies in neurological disorders. This article has attempted to understand the impact of mitochondrial function and mitochondrial dysfunction in the pathogenesis of brain disorders to develop potential therapeutic drugs.
Mitochondria are important organelles for high energy synthesis, reactive oxygen species balancing, antiapoptotic molecule production, membrane stability, intracellular calcium buffering, neuroplasticity and neurotransmission. Dysfunction in mitochondria is considered to be involved in the pathophysiology of mental problems. It has been observed that several drug types used to treat brain illnesses can harm mitochondria by altering the oxidative phosphorylation system and the gene expression of mitochondria-related proteins. In some studies, it has been observed that mitochondrial biogenesis shows a therapeutic effect in the management of mitochondrial disorders. Many therapeutic compounds are effective in the activation of mitochondrial biogenesis. The comorbidity of mental problems observed in those with mitochondrial dysfunction and the change in the efficacy of the cellular respiratory system have attracted researchers to understand the pathways and possible therapeutic strategies in neurological disorders. This article has attempted to understand the impact of mitochondrial function and mitochondrial dysfunction in the pathogenesis of brain disorders to develop potential therapeutic drugs.
Fernandoa adenophylla (FA, Heterophragma adenophyllum) is a plant, cultivated throughout Africa and Southeast Asia. It contains potent phytochemicals such as novel naphthoquinones, their derivatives (peshwaraquinone, dilapachone, adenophyllone, indadone, and lapachol), and triterpenoids [ursolic acid (UA), β-sitosterol (BS), α-amyrin, and oleanolic acid (OA)] that have been assessed and reported to show potential pharmacological activities. The crude extract obtained from the plant has been investigated for certain pharmacological activities such as antibacterial, antifungal, anti-tubercular (TB), antihypertensive, and leishmanicidal activity. A novel drug delivery systems (NDDS) is the latest technique that combines innovative development, formulations, new technology, and methodologies for the safe delivery of pharmaceutical substances in the body. The present study reports the possible treatment opportunities of FA and recent possible novel drug delivery approaches for the natural medicinal phytochemicals.
Fernandoa adenophylla (FA, Heterophragma adenophyllum) is a plant, cultivated throughout Africa and Southeast Asia. It contains potent phytochemicals such as novel naphthoquinones, their derivatives (peshwaraquinone, dilapachone, adenophyllone, indadone, and lapachol), and triterpenoids [ursolic acid (UA), β-sitosterol (BS), α-amyrin, and oleanolic acid (OA)] that have been assessed and reported to show potential pharmacological activities. The crude extract obtained from the plant has been investigated for certain pharmacological activities such as antibacterial, antifungal, anti-tubercular (TB), antihypertensive, and leishmanicidal activity. A novel drug delivery systems (NDDS) is the latest technique that combines innovative development, formulations, new technology, and methodologies for the safe delivery of pharmaceutical substances in the body. The present study reports the possible treatment opportunities of FA and recent possible novel drug delivery approaches for the natural medicinal phytochemicals.
Systemic lupus erythematosus (SLE) is a chronic, immune-mediated disease associated with significant morbidity and mortality. New evidence suggests that diet, gut microbiota, intestinal permeability, and endotoxemia may modulate chronic inflammation and disease activity in SLE. This review focus on what is known about the gut microbiota in lupus mouse models and SLE patients and the possible mechanisms that connect the gut microbiota with SLE. It included 29 studies (12 animal studies, 15 human studies, and 2 included data on both), with variable results regarding alpha and beta-diversity and gut microbiota composition between lupus-mouse models and SLE patients. Ruminococcus (R.) gnavus was significantly increased in lupus nephritis (LN) in one study, but this was not corroborated by others. Despite the different results, mechanistic lupus mouse model studies have shown that gut microbiota can modulate disease activity. Interestingly, pathobiont translocation in monocolonized and autoimmune-prone mice induced autoantibodies and caused mortality, which could be prevented by a vaccine targeting the pathobiont. Moreover, studies on fecal transplants and diet on different lupus mouse models showed an effect on disease activity. In SLE patients, a higher adherence to the Mediterranean diet was associated with lower disease activity, which may be explained by the connection between diet and gut microbiota. Although gut dysbiosis has been observed in SLE patients and lupus mouse models, it remains to clarify if it is a cause or a consequence of the disease or its treatments. Further studies with larger and well-characterized populations will undoubtedly contribute to deciphering the role of gut microbiota in SLE development, progression, and outcome.
Systemic lupus erythematosus (SLE) is a chronic, immune-mediated disease associated with significant morbidity and mortality. New evidence suggests that diet, gut microbiota, intestinal permeability, and endotoxemia may modulate chronic inflammation and disease activity in SLE. This review focus on what is known about the gut microbiota in lupus mouse models and SLE patients and the possible mechanisms that connect the gut microbiota with SLE. It included 29 studies (12 animal studies, 15 human studies, and 2 included data on both), with variable results regarding alpha and beta-diversity and gut microbiota composition between lupus-mouse models and SLE patients. Ruminococcus (R.) gnavus was significantly increased in lupus nephritis (LN) in one study, but this was not corroborated by others. Despite the different results, mechanistic lupus mouse model studies have shown that gut microbiota can modulate disease activity. Interestingly, pathobiont translocation in monocolonized and autoimmune-prone mice induced autoantibodies and caused mortality, which could be prevented by a vaccine targeting the pathobiont. Moreover, studies on fecal transplants and diet on different lupus mouse models showed an effect on disease activity. In SLE patients, a higher adherence to the Mediterranean diet was associated with lower disease activity, which may be explained by the connection between diet and gut microbiota. Although gut dysbiosis has been observed in SLE patients and lupus mouse models, it remains to clarify if it is a cause or a consequence of the disease or its treatments. Further studies with larger and well-characterized populations will undoubtedly contribute to deciphering the role of gut microbiota in SLE development, progression, and outcome.
Whipple’s disease (WD) is a rare systemic disease caused by gram-positive bacillus bacteria that invades multiple organs mainly the intestinal epithelium. Its manifestation is not only limited to the gastrointestinal tract but it also affects the joints, muscle and skin. This is a case of a 54-year-old male patient with a medical history of chronic arthritis presenting with bilateral progressive calves pain, anterior tibial hyperpigmentation, joints pain, anemia and weight loss. He was misdiagnosed as rheumatoid arthritis, for which he was treated by immunosuppressors for several years with no amelioration. After advanced investigations, he was found to have multiple retroperitoneal and mesenteric adenopathies, with an incidental finding of a mesojejunal mass during laparoscopy, from which the biopsies revealed the presence of histiocytosis and numerous intra-cytoplasmic particles with positive periodic acid–Schiff (PAS) suggesting the diagnosis of WD. Endoscopy was done and intestinal histology with polymerase chain reaction (PCR) test confirmed the diagnosis of WD. The patient was then treated with antibiotics (ceftriaxone and trimethoprim-sulfamethoxazole) with a remarkable clinical amelioration. To be aware of WD as a potential etiology behind malabsorption, musculoskeletal and skin abnormalities, is the first step in order to establish the diagnosis and provide adequate treatment, thus, improving the patient’s quality of life. WD is a rare, without antibiotic treatment deadly systemic infectious disease caused by the ubiquitary Gram-positive bacterium Tropheryma whipplei. This article aims to report a case marked with dermatomyositis like presentation that had a missed and delayed diagnosis.
Whipple’s disease (WD) is a rare systemic disease caused by gram-positive bacillus bacteria that invades multiple organs mainly the intestinal epithelium. Its manifestation is not only limited to the gastrointestinal tract but it also affects the joints, muscle and skin. This is a case of a 54-year-old male patient with a medical history of chronic arthritis presenting with bilateral progressive calves pain, anterior tibial hyperpigmentation, joints pain, anemia and weight loss. He was misdiagnosed as rheumatoid arthritis, for which he was treated by immunosuppressors for several years with no amelioration. After advanced investigations, he was found to have multiple retroperitoneal and mesenteric adenopathies, with an incidental finding of a mesojejunal mass during laparoscopy, from which the biopsies revealed the presence of histiocytosis and numerous intra-cytoplasmic particles with positive periodic acid–Schiff (PAS) suggesting the diagnosis of WD. Endoscopy was done and intestinal histology with polymerase chain reaction (PCR) test confirmed the diagnosis of WD. The patient was then treated with antibiotics (ceftriaxone and trimethoprim-sulfamethoxazole) with a remarkable clinical amelioration. To be aware of WD as a potential etiology behind malabsorption, musculoskeletal and skin abnormalities, is the first step in order to establish the diagnosis and provide adequate treatment, thus, improving the patient’s quality of life. WD is a rare, without antibiotic treatment deadly systemic infectious disease caused by the ubiquitary Gram-positive bacterium Tropheryma whipplei. This article aims to report a case marked with dermatomyositis like presentation that had a missed and delayed diagnosis.
To investigate the relationship between the incidence of contrast-induced acute kidney injury (CI-AKI) and the level of small dense low-density lipoprotein (sd-LDL) and systemic immune-inflammation index (SII) in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing emergency percutaneous coronary intervention (PCI), and to further compare the predictive values of SII, sd-LDL and their combination for CI-AKI.
A total of 674 patients were assigned to a training and a validation cohort according to their chronological sequence. The baseline characteristics of the 450 patients in the training cohort were considered as candidate univariate predictors of CI-AKI. Multivariate logistic regression was then used to identify predictors of CI-AKI and develop a prediction model. The predictive values of SII, sd-LDL and their combination for CI-AKI were also evaluated.
Multivariate logistic regression analysis showed that age, left ventricular ejection fraction (LVEF), sd-LDL, uric acid, estimated glomerular filtration rate (eGFR) and SII were predictors of CI-AKI. The area under the curve (AUC) of the prediction model based on the above factors was 0.846 [95% confidence interval (CI) 0.808–0.884], and the Hosmer-Lemeshow test (P = 0.587, χ2 = 6.543) proved the goodness of fit of the model. The AUC combining SII with sd-LDL to predict CI-AKI was 0.785 (95% CI 0.735–0.836), with a sensitivity of 72.8% and a specificity of 79.8%, and was statistically significant when compared with SII and sd-LDL, respectively. The predictive efficiency of combining SII with sd-LDL and SII were evaluated by improved net reclassification improvement (NRI, 0.325, P < 0.001) and integrated discrimination improvement (IDI, 0.07, P < 0.001).
Both SII and sd-LDL can be used as predictors of CI-AKI in STEMI patients undergoing emergency PCI, and their combination can provide more useful value for early assessment of CI-AKI.
To investigate the relationship between the incidence of contrast-induced acute kidney injury (CI-AKI) and the level of small dense low-density lipoprotein (sd-LDL) and systemic immune-inflammation index (SII) in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing emergency percutaneous coronary intervention (PCI), and to further compare the predictive values of SII, sd-LDL and their combination for CI-AKI.
A total of 674 patients were assigned to a training and a validation cohort according to their chronological sequence. The baseline characteristics of the 450 patients in the training cohort were considered as candidate univariate predictors of CI-AKI. Multivariate logistic regression was then used to identify predictors of CI-AKI and develop a prediction model. The predictive values of SII, sd-LDL and their combination for CI-AKI were also evaluated.
Multivariate logistic regression analysis showed that age, left ventricular ejection fraction (LVEF), sd-LDL, uric acid, estimated glomerular filtration rate (eGFR) and SII were predictors of CI-AKI. The area under the curve (AUC) of the prediction model based on the above factors was 0.846 [95% confidence interval (CI) 0.808–0.884], and the Hosmer-Lemeshow test (P = 0.587, χ2 = 6.543) proved the goodness of fit of the model. The AUC combining SII with sd-LDL to predict CI-AKI was 0.785 (95% CI 0.735–0.836), with a sensitivity of 72.8% and a specificity of 79.8%, and was statistically significant when compared with SII and sd-LDL, respectively. The predictive efficiency of combining SII with sd-LDL and SII were evaluated by improved net reclassification improvement (NRI, 0.325, P < 0.001) and integrated discrimination improvement (IDI, 0.07, P < 0.001).
Both SII and sd-LDL can be used as predictors of CI-AKI in STEMI patients undergoing emergency PCI, and their combination can provide more useful value for early assessment of CI-AKI.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can engender multi-system inflammatory syndrome. Its main symptoms are cardiovascular and thromboembolic problems that can develop into severe complications. The present case is about a 55-year-old patient who was admitted for critical ischemia of the right lower limb and necrosis of the right forefoot. The patient was infected with coronavirus disease 2019 (COVID-19) one month before her admission. The patient also has cardiovascular risks including type 2 diabetes and hypertension. The performance of ultrasounds revealed a thrombus in the right atrium and the pulmonary artery, and arteriography detected an occlusion of the right popliteal joint for which she had an endovascular recanalization and amputation of the right forefoot. This case highlights that SARS-CoV-2 infection could be considered a serious cardiovascular disease requiring cardiovascular explorations to initiate hospital management and avoid severe complications.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can engender multi-system inflammatory syndrome. Its main symptoms are cardiovascular and thromboembolic problems that can develop into severe complications. The present case is about a 55-year-old patient who was admitted for critical ischemia of the right lower limb and necrosis of the right forefoot. The patient was infected with coronavirus disease 2019 (COVID-19) one month before her admission. The patient also has cardiovascular risks including type 2 diabetes and hypertension. The performance of ultrasounds revealed a thrombus in the right atrium and the pulmonary artery, and arteriography detected an occlusion of the right popliteal joint for which she had an endovascular recanalization and amputation of the right forefoot. This case highlights that SARS-CoV-2 infection could be considered a serious cardiovascular disease requiring cardiovascular explorations to initiate hospital management and avoid severe complications.
In a number of malignancies, new immuno-oncology therapies that focus on the programmed cell death 1 (PD-1) have improvised the patient condition along with a positive aftereffect. Monoclonal antibodies (mAbs) directed against PD-1 and its ligand (PD-L1), have been widely used to treat a variety of malignancies, including melanoma, renal cancer, and non-small cell lung cancer (NSCLC). Dostarlimab, a therapeutic anti-PD-1 antibody, was authorised by the United States Food and Drug Administration (FDA) in April 2021 under the trade name JEMPERLI. It is a humanised contrary PD-1 immunoglobulin G 4 (IgG4) mAb, which successfully blocks interaction with PD-L1 and PD-L2 by binding tightly to the PD-1 receptor. This article summarizes the different aspects associated with the dostarlimab, including currently available anti-PD-1/PD-L1 antibodies, pharmacokinetics (PK), pharmacodynamics, adverse reaction, and mechanism of action of dostarlimab, as well as various reported clinical trials.
Role of dostarlimab in cancer
In a number of malignancies, new immuno-oncology therapies that focus on the programmed cell death 1 (PD-1) have improvised the patient condition along with a positive aftereffect. Monoclonal antibodies (mAbs) directed against PD-1 and its ligand (PD-L1), have been widely used to treat a variety of malignancies, including melanoma, renal cancer, and non-small cell lung cancer (NSCLC). Dostarlimab, a therapeutic anti-PD-1 antibody, was authorised by the United States Food and Drug Administration (FDA) in April 2021 under the trade name JEMPERLI. It is a humanised contrary PD-1 immunoglobulin G 4 (IgG4) mAb, which successfully blocks interaction with PD-L1 and PD-L2 by binding tightly to the PD-1 receptor. This article summarizes the different aspects associated with the dostarlimab, including currently available anti-PD-1/PD-L1 antibodies, pharmacokinetics (PK), pharmacodynamics, adverse reaction, and mechanism of action of dostarlimab, as well as various reported clinical trials.
Role of dostarlimab in cancer
In recent years, Polypodium leucotomos has emerged with a great interest for having medicinal and therapeutic potential. It is producing very promising results due to the presence of antioxidant and photoprotective properties. Electronic libraries and databases, including Scopus, PubMed, Google Scholar, Science Direct, and Web of Science were searched to identify relevant studies; 79 publications contributed to this review regarding Polypodium leucotomos botanical aspects, chemical composition, antioxidant and photoprotective activity. It is used in complementary and alternative therapies with various pharmaceutical dosage forms (systemic or topical). Thanks to the composition of phytochemical constituents present in the leaves and rhizomes which confer antioxidant and photoprotective activity that has clinical therapeutic potential to be used as systemic and topical sunscreen of natural origin for the prevention of different types of skin diseases caused by harmful ultraviolet A and ultraviolet B radiations. However, more studies are needed in the future to test the ability and enhance the capacity of sunscreen and sunblock in cosmetic formulations. To conclude, it is recommended to carry out scientific studies based on different analytical methods to evaluate the phytoconstituents potential and to develop stable pharmaceutical formulations according to the skin phototype.
In recent years, Polypodium leucotomos has emerged with a great interest for having medicinal and therapeutic potential. It is producing very promising results due to the presence of antioxidant and photoprotective properties. Electronic libraries and databases, including Scopus, PubMed, Google Scholar, Science Direct, and Web of Science were searched to identify relevant studies; 79 publications contributed to this review regarding Polypodium leucotomos botanical aspects, chemical composition, antioxidant and photoprotective activity. It is used in complementary and alternative therapies with various pharmaceutical dosage forms (systemic or topical). Thanks to the composition of phytochemical constituents present in the leaves and rhizomes which confer antioxidant and photoprotective activity that has clinical therapeutic potential to be used as systemic and topical sunscreen of natural origin for the prevention of different types of skin diseases caused by harmful ultraviolet A and ultraviolet B radiations. However, more studies are needed in the future to test the ability and enhance the capacity of sunscreen and sunblock in cosmetic formulations. To conclude, it is recommended to carry out scientific studies based on different analytical methods to evaluate the phytoconstituents potential and to develop stable pharmaceutical formulations according to the skin phototype.
The aim of this review is to discuss the development of nanostructured lipid carrier (NLC) by the application of quality by design (QbD). QbD started with the evolution of the quality concept and slow adaptation of quality guidelines, which has now become a regulatory requirement. In this review, brief history and elements of QbD including risk assessment (RA) have been discussed followed by the design of experiments (DoEs) that acts as a tool to analyze the input whose variation can optimize the output with the desired goal. NLC is a versatile delivery system as researchers widely use it to administer therapeutics with different physicochemical properties. The surface of NLC can be modified, making it a suitable delivery system with targeting potential for therapeutics. Implementation of QbD provides a high-quality robust formulation that can consistently meet the patient’s requirement throughout its life cycle without compromising the safety and effectiveness of the drug and delivery system. This review discusses QbD concepts followed by the systematic development of NLC by the application of DoE. Process analytical technology (PAT) and six sigma concepts have also been included which can benefit in the development of optimized NLC.
The aim of this review is to discuss the development of nanostructured lipid carrier (NLC) by the application of quality by design (QbD). QbD started with the evolution of the quality concept and slow adaptation of quality guidelines, which has now become a regulatory requirement. In this review, brief history and elements of QbD including risk assessment (RA) have been discussed followed by the design of experiments (DoEs) that acts as a tool to analyze the input whose variation can optimize the output with the desired goal. NLC is a versatile delivery system as researchers widely use it to administer therapeutics with different physicochemical properties. The surface of NLC can be modified, making it a suitable delivery system with targeting potential for therapeutics. Implementation of QbD provides a high-quality robust formulation that can consistently meet the patient’s requirement throughout its life cycle without compromising the safety and effectiveness of the drug and delivery system. This review discusses QbD concepts followed by the systematic development of NLC by the application of DoE. Process analytical technology (PAT) and six sigma concepts have also been included which can benefit in the development of optimized NLC.
Extensive research is carried out throughout the world in healthy persons with obesity phenotype in concern with prevalence, metabolic profiling, etc. To the best of the authors’ knowledge, not many studies have investigated the status of adiponectin, specific inflammatory changes, oxidative damage in healthy adolescents and young adults with obesity. Present study was undertaken in adolescents and young adults of urban population in a district of North Karnataka, India, in a view to understand relationship between hormone adiponectin, oxidative stress markers like C3, C4, high sensitivity C-reactive protein (hs-CRP) in non-hypertensive, non-diabetic, euthyroid individuals with and without obesity.
Participant selection was done using cluster sampling technique. Participating adolescents and young adults, each with and without obesity were included in the study. Screening of participants for diabetes, hypertension, and thyroid disorders was done, their serum level of adiponectin, hs-CRP, C3, C4, ceruloplasmin (Cp), thiobarbituric acid reactive substances (TBARS), and total antioxidant capacity (TAC) were estimated using standardized methods in National Accreditation Board for Testing and Calibration Laboratories (NABL) laboratory.
Adiponectin (young adults lower than adolescents, P = 0.01) levels were low, while hs-CRP and Cp (young adults higher than adolescents, P = 0.01) levels were high with increasing age in non-obese. While in persons having obesity, aging adiponectin levels were low while hs-CRP, C3, Cp levels were high significantly. Females without obesity had significantly higher values of C3 than males. Adiponectin showed higher levels in females than males, however, statistical significance could not be achieved (P = 0.308). While females with obesity, exhibited statistically lower levels of adiponectin, and higher levels of C3 and C4.
Being non-diabetic and non-hypertensive yet obese, tagged by one time of assay, does not suffice to be categorized as healthy. Healthy young adults with obesity are exhibiting lower levels of adiponectin and higher levels of inflammatory and oxidative stress markers compared to adolescents with obesity. This implies, the so categorized “healthy obese” participants are in a phase of transition towards an unhealthy state.
Extensive research is carried out throughout the world in healthy persons with obesity phenotype in concern with prevalence, metabolic profiling, etc. To the best of the authors’ knowledge, not many studies have investigated the status of adiponectin, specific inflammatory changes, oxidative damage in healthy adolescents and young adults with obesity. Present study was undertaken in adolescents and young adults of urban population in a district of North Karnataka, India, in a view to understand relationship between hormone adiponectin, oxidative stress markers like C3, C4, high sensitivity C-reactive protein (hs-CRP) in non-hypertensive, non-diabetic, euthyroid individuals with and without obesity.
Participant selection was done using cluster sampling technique. Participating adolescents and young adults, each with and without obesity were included in the study. Screening of participants for diabetes, hypertension, and thyroid disorders was done, their serum level of adiponectin, hs-CRP, C3, C4, ceruloplasmin (Cp), thiobarbituric acid reactive substances (TBARS), and total antioxidant capacity (TAC) were estimated using standardized methods in National Accreditation Board for Testing and Calibration Laboratories (NABL) laboratory.
Adiponectin (young adults lower than adolescents, P = 0.01) levels were low, while hs-CRP and Cp (young adults higher than adolescents, P = 0.01) levels were high with increasing age in non-obese. While in persons having obesity, aging adiponectin levels were low while hs-CRP, C3, Cp levels were high significantly. Females without obesity had significantly higher values of C3 than males. Adiponectin showed higher levels in females than males, however, statistical significance could not be achieved (P = 0.308). While females with obesity, exhibited statistically lower levels of adiponectin, and higher levels of C3 and C4.
Being non-diabetic and non-hypertensive yet obese, tagged by one time of assay, does not suffice to be categorized as healthy. Healthy young adults with obesity are exhibiting lower levels of adiponectin and higher levels of inflammatory and oxidative stress markers compared to adolescents with obesity. This implies, the so categorized “healthy obese” participants are in a phase of transition towards an unhealthy state.
One single nucleotide polymorphism (SNP) rs738409 in the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene has been considered a major genetic risk factor of nonalcoholic fatty liver disease (NAFLD). Data have indicated that NAFLD is related to insulin resistance and dyslipidemia, but whether rs738409 is associated with circulating lipid and lipoproteins is not fully elucidated. The main aim of this study was to assess the association of rs738409 with lipid and lipoprotein levels in patients with dyslipidemia.
This was a post-hoc analysis of a study in patients with dyslipidemia recruited on an outpatient basis. Morning blood samples were collected after a 12-h fast. Genomic DNA was extracted from whole-blood samples.
One hundred seventy-five patients with dyslipidemia were included (97 women). Lipid levels [total cholesterol (TC), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C)] or glycosylated hemoglobin (HbA1c) were not associated with the SNP, even after adjustment for gender, body mass index (BMI) and type 2 diabetes mellitus (T2DM), using either the additive (CC vs. CG vs. GG) or the dominant (CC vs. GG + CG) inheritance model. When data were stratified for obesity, significant associations between the variant and TC (P = 0.014) or LDL-C levels (P = 0.046) in the non-obese were observed. Pairwise comparison revealed significant changes only in TC between CC and CG genotypes (P = 0.012).
No association was shown between rs738409 SNP and lipid/lipoprotein levels in patients with dyslipidemia. In subgroup analysis, TC was higher in non-obese, but not in obese, patients with CC, compared to CG carriers.
One single nucleotide polymorphism (SNP) rs738409 in the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene has been considered a major genetic risk factor of nonalcoholic fatty liver disease (NAFLD). Data have indicated that NAFLD is related to insulin resistance and dyslipidemia, but whether rs738409 is associated with circulating lipid and lipoproteins is not fully elucidated. The main aim of this study was to assess the association of rs738409 with lipid and lipoprotein levels in patients with dyslipidemia.
This was a post-hoc analysis of a study in patients with dyslipidemia recruited on an outpatient basis. Morning blood samples were collected after a 12-h fast. Genomic DNA was extracted from whole-blood samples.
One hundred seventy-five patients with dyslipidemia were included (97 women). Lipid levels [total cholesterol (TC), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C)] or glycosylated hemoglobin (HbA1c) were not associated with the SNP, even after adjustment for gender, body mass index (BMI) and type 2 diabetes mellitus (T2DM), using either the additive (CC vs. CG vs. GG) or the dominant (CC vs. GG + CG) inheritance model. When data were stratified for obesity, significant associations between the variant and TC (P = 0.014) or LDL-C levels (P = 0.046) in the non-obese were observed. Pairwise comparison revealed significant changes only in TC between CC and CG genotypes (P = 0.012).
No association was shown between rs738409 SNP and lipid/lipoprotein levels in patients with dyslipidemia. In subgroup analysis, TC was higher in non-obese, but not in obese, patients with CC, compared to CG carriers.