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Severe acute respiratory syndrome coronavirus 2-like other viral infections cause temporary immunosuppressive effects. This COVID-19 infection-induced temporary suppression of cellular immunity can predispose to infections like fungal. Furthermore, high-dose corticosteroids used in COVID-19 management can trigger or accelerate fungal infections. This case series presents the clinicomicrobiological profile of a few such admitted cases, as it is very important for all clinicians and clinical microbiologists to keep the new yet recently not-so-uncommon entities in mind while evaluating a patient.

Continuous revision of the histologic and stage-wise classification of lung cancer by the World Health Organization (WHO) provides the foundation for therapeutic advances by promoting molecular targeted and immunotherapies and ensuring accurate diagnosis. Cancer epidemiologic data provide helpful information for cancer prevention, diagnosis, and management, supporting health-care interventions. Global cancer mortality projections from 2016 to 2060 show that cancer will overtake ischemic heart diseases (IHD) as the leading cause of death (18.9 million) immediately after 2030, surpassing non-small cell lung cancer (NSCLC), which accounts for 85 percent of lung cancers. The clinical stage at the diagnosis is the main prognostic factor in NSCLC therapies. Advanced early diagnostic methods are essential as the initial stages of cancer show reduced mortality compared to the advanced stages. Sophisticated approaches to proper histological classification and NSCLC management have improved clinical efficiency. Although immune checkpoint inhibitors (ICIs) and targeted molecular therapies have refined the therapeutic management of late-stage NSCLC, the specificity and sensitivity of cancer biomarkers should be improved by focusing on prospective studies, followed by their use as therapeutic tools. The liquid biopsy candidates such as circulating tumor cells (CTCs), circulating cell-free tumor DNA (cfDNA), tumor educated platelets (TEP), and extracellular vesicles (EVs) possess cancer-derived biomolecules and aid in tracing: driver mutations leading to cancer, acquired resistance caused by various generations of therapeutic agents, refractory disease, prognosis, and surveillance.

Introduction: Orofacial cleft (OFC) has been one of the major common congenital anomalies exhibiting prominent ramifications allied with the medical, social, psychological, and economic strands. Most OFC occurrences do not have additional features, so they are categorized as nonsyndromic. The classification of the aforesaid complication has been directed toward the following categories: cleft lip (CL) with cleft palate, isolated CL, and finally the isolated cleft palate. The recent research concerning the aforementioned anomalies always searches for advanced novel inferences linked with the chromosomal perspectives since some of the specific genes are probably known to produce significant effects over the anomalies. Materials and Methods: Karyotyping was performed for all 130 cases of nonsyndromic cleft lip and palate (NSCLP). Aseptic collection of peripheral blood lymphocyte culture (PBLC) was performed from the patients using heparin vacutainers, and C-banding was done to confirm heterochromatic variations. Results: A total of 130 patients known to have the NSCLP were recruited for this study of which 88 cases (68%) had CL along with cleft palate, 18 cases (14%) had isolated CL and 24 cases (18%) had isolated cleft palate. Cytogenetic analysis by G-banding by Trypsin and Giemsa (GTG) banding in these patients revealed five cases (3.84%) with abnormal karyotype where a higher frequency of pericentric inversion in the analyzed region, specifically the chromosome 9, inv(9)(p11p13) was observed. Conclusion: The heteromorphisms or structural rearrangements involving the centromere were confirmed by centromere banding in two cases. Understanding the etiology with special inference on the above-said perspectives is significant to develop an effective strategy for the prevention and treatment of the individuals affected with the anomalies.

Background: Vaccine effectiveness for first-generation coronavirus disease (COVID-19) vaccines among People Living with HIV (PLHIV) in India remains unexplored. This study entails the estimation of the real-world effectiveness of COVID-19 vaccines (AZD1222/Covishield, BBV152/Covaxin) among PLHIV and the identification of variants of SARS-CoV-2 among those infected with COVID-19. Methods: An ambi-directional cohort study was conducted among 925 PLHIV above 18 years of age in two districts of central Kerala, India, from February 2022 to March 2023. Selected PLHIV were recruited as Participant Liaison Officers (PLOs) for the follow-up on the study participants. At enrolment, basic details, baseline CD4 count, and a Nasopharyngeal (NP) swab for RT-PCR were collected. In the follow-up phase, NP swabs were collected from subjects with COVID-19 symptoms. Positive subjects had a CD4 count and genomic sequencing performed. Results: The mean age of the participants was 46.93 ± 11.00 years. The majority, 819 (93.6%), of participants had received at least one dose of any vaccine, while 56 (6.4%) were unvaccinated. A total of 649 (79.24%) participants were vaccinated with Covishield and 169 (20.63%) with Covaxin. In the vaccinated group, 158 (19.3%) reported COVID-19 infection. Vaccine Effectiveness (VE) for one dose of any vaccine was 43.2% (95% CI: 11.8–64.5), p = 0.015. The effectiveness of full vaccination with Covishied was 63.8% (95% CI: 39.3–79.2), p < 0.001, and Covaxin was 73.4% (95% CI: 44.3–87.3). VE was highest, at 60.7% (95% CI: 23.6–81.3), when the two doses of the vaccine were given at an interval of less than 6 weeks. Participants with a baseline CD4 count > 350 had greater protection from COVID-19, at 53.4% (95% CI: 19.6–75.3) p = 0.004. The incident cases were sub-variants of Omicron (BA.2, BA.2.38, BA.2.10). Conclusions: Full vaccination with Covishield and Covaxin was effective against COVID-19 infection among PLHIV on treatment; albeit, that of Covaxin was higher. A gap of 4 to 6 weeks between the two doses of COVID-19 vaccine was found to have higher VE among PLHIV.

Placental complication arises due to various risk factors occurring during the pregnancy period, leading to an increased morbidity rate. Placenta related disorders are one of primary reason for pregnancy related complications and the clinical incidences are seen to be on the rise. Most of the common disorders associated with placenta are pre-eclampsia, recurrent spontaneous abortions, intra-uterine growth restriction etc. Several studies have been done to understand the genetics and immunological attributes leading to the development of placenta associated complications. In the recent years, studies were able to establish and identify ncRNAs found specifically in foetal tissues such as the placenta. The aberrant expression patterns of ncRNA associated with placenta has been linked to disorders such as pre-eclampsia. Since ncRNA play a major role in regulating biological processes like trophoblast growth, migration and invasion, their aberrant expression could very well lead to complications like spontaneous pregnancy loss. This review article focuses on the association of ncRNAs - miRNAs, lncRNAs, CircRNAs in placenta associated complications as well as the different ncRNA based therapies. Deciphering the exact mechanism involved in the regulation and development of placenta through ncRNA will help in using it as a biomarker for early diagnosis. Understanding the therapeutic opportunities of ncRNAs in placental disorders will result in better treatment strategies.

Infection with viruses, bacteria, and parasites are thought to be the underlying cause of about 8–17% of the world’s cancer burden, i.e., approximately one in every five malignancies globally is caused by an infectious pathogen. Oncogenesis is thought to be aided by eleven major pathogens. It is crucial to identify microorganisms that potentially act as human carcinogens and to understand how exposure to such pathogens occur as well as the following carcinogenic pathways they induce. Gaining knowledge in this field will give important suggestions for effective pathogen-driven cancer care, control, and, ultimately, prevention. This review will mainly focus on the major onco-pathogens and the types of cancer caused by them. It will also discuss the major pathways which, when altered, lead to the progression of these cancers.

Background and Aim: People with inflammatory bowel disease (IBD) have an increased risk of cardiovascular disease, including in younger adulthood. This may arise in part from chronic, systemic low‐grade inflammation. The process of atherosclerosis may begin in childhood. We sought to determine whether pediatric IBD is associated with adverse changes in arterial structure and function as a marker of early increased cardiovascular risk. Methods: We performed a case–control study comparing children with IBD for a median disease duration of 2.49 (interquartile range 1.23, 4.38) years with healthy children. In a single visit, we collected baseline clinical and anthropometric data, and measured blood pressure, pulse wave velocity, carotid artery distensibility, and aortic and carotid intima‐media thickness. High‐sensitivity C‐reactive protein and fasting lipids were measured. Results: We enrolled 81 children with IBD (40 with Crohn's disease, 40 with ulcerative colitis, and 1 with unspecified IBD) and 82 control participants. After adjusting for age, sex, body mass index z‐score, blood pressure, and low‐density lipoprotein cholesterol, there was no difference in measures of arterial structure and function in children with IBD compared with controls, nor between those with Crohn's disease or ulcerative colitis. Conclusion: We did not show any differences in arterial structure and function in children with a history of IBD for less than 5 years compared with healthy controls. IBD diagnosed in childhood may provide a window of opportunity to actively reduce standard cardiovascular risk factors and improve future cardiovascular outcomes. [ABSTRACT FROM AUTHOR]

Despite the progress in the comprehension of LC progression, risk, immunologic control, and treatment choices, it is still the primary cause of cancer-related death. LC cells possess a very low and heterogeneous antigenicity, which allows them to passively evade the anticancer defense of the immune system by educating cytotoxic lymphocytes (CTLs), tumor-infiltrating lymphocytes (TILs), regulatory T cells (Treg), immune checkpoint inhibitors (ICIs), and myeloid-derived suppressor cells (MDSCs). Though ICIs are an important candidate in first-line therapy, consolidation therapy, adjuvant therapy, and other combination therapies involving traditional therapies, the need for new predictive immunotherapy biomarkers remains. Furthermore, ICI-induced resistance after an initial response makes it vital to seek and exploit new targets to benefit greatly from immunotherapy. As ICIs, tumor mutation burden (TMB), and microsatellite instability (MSI) are not ideal LC predictive markers, a multi-parameter analysis of the immune system considering tumor, stroma, and beyond can be the future-oriented predictive marker. The optimal patient selection with a proper adjuvant agent in immunotherapy approaches needs to be still revised. Here, we summarize advances in LC immunotherapy approaches with their clinical and preclinical trials considering cancer models and vaccines and the potential of employing immunology to predict immunotherapy effectiveness in cancer patients and address the viewpoints on future directions. We conclude that the field of lung cancer therapeutics can benefit from the use of combination strategies but with comprehension of their limitations and improvements.

Oral cancer is a significant non-communicable disease affecting both emergent nations and developed countries. Squamous cell carcinoma of the head and neck represent the eight major familiar cancer types worldwide, accounting for more than 350,000 established cases every year. Oral cancer is one of the most exigent tumors to control and treat. The survival rate of oral cancer is poor due to local invasion along with recurrent lymph node metastasis. The tumor microenvironment contains a different population of cells, such as fibroblasts associated with cancer, immune-infiltrating cells, and other extracellular matrix non-components. Metastasis in a primary site is mainly due to multifaceted progression known as epithelial-to-mesenchymal transition (EMT). For the period of EMT, epithelial cells acquire mesenchymal cell functional and structural characteristics, which lead to cell migration enhancement and promotion of the dissemination of tumor cells. The present review links the tumor microenvironment and the role of EMT in inflammation, transcriptional factors, receptor involvement, microRNA, and other signaling events. It would, in turn, help to better understand the mechanism behind the tumor microenvironment and EMT during oral cancer.

Heavy metals and metalloids like cadmium, arsenic, mercury, and lead are frequently found in the soil, water, food, and atmosphere; trace amounts can cause serious health issues to the human organism. These toxic trace elements (TTE) affect almost all the organs, mainly the heart, kidney, liver, lungs, and the nervous system, through increased free radical formation, DNA damage, lipid peroxidation, and protein sulfhydryl depletion. This work aims to advance our understanding of the mechanisms behind lipid accumulation via increased free fatty acid levels in circulation due to TTEs. The increased lipid level in the myocardium worsens the heart function. This dysregulation of the lipid metabolism leads to damage in the structure of the myocardium, inclusive fibrosis in cardiac tissue, myocyte apoptosis, and decreased contractility due to mitochondrial dysfunction. Additionally, it is discussed herein how exposure to cadmium decreases the heart rate, contractile tension, the conductivity of the atrioventricular node, and coronary flow rate. Arsenic may induce atherosclerosis by increasing platelet aggregation and reducing fibrinolysis, as exposure interferes with apolipoprotein (Apo) levels, resulting in the rise of the Apo-B/Apo-A1 ratio and an elevated risk of acute cardiovascular events. Concerning mercury and lead, these toxicants can cause hypertension, myocardial infarction, and carotid atherosclerosis, in association with the generation of free radicals and oxidative stress. This review offers a complete overview of the critical factors and biomarkers of lipid and TTE-induced cardiotoxicity useful for developing future protective interventions.

Abstract: Blood cell membranes in sickle cell disease (SCD) have low docosahexaenoic acid (DHA). DHA treatment reduces sickle cell crisis (SCC) rate and ameliorates the inflammation, oxidative stress, and hypercoagulable state of SCD. SC411 is a novel DHA ethyl ester formulation with a proprietary delivery platform (Advanced Lipid Technology) that enhances DHA bioavailability. The SCOT trial investigated the effect of 3 different doses of SC411 on clinical and biochemical endpoints in 67 children with SCD (5-17 years old). Seventy-six percent of subjects were also receiving hydroxyurea. After 4 weeks of treatment with SC411 at 20, 36, and 60 mg DHA/kg per day or placebo a statistically significant (P < .001) mean percentage increase of blood cell membrane DHA and eicosapentaenoic acid was seen vs baseline: 109.0% (confidence interval [CI], 46.7-171.3), 163.8% (CI, 108.3-219.2), 170.8% (CI, 90.2-251.4), and 28.6% (CI, 250.1 to 107.3), respectively. After 8 weeks of treatment, statistically significant changes vs placebo were also observed in D-dimer (P = .025) and soluble E-selectin (P = .0219) in subjects exposed to 36 mg/kg. A significant increase in hemoglobin was observed against placebo in subjects receiving 20 mg DHA/kg per day (P = .039). SC411 significantly reduced electronic diary recorded SCC, analgesic use at home, and days absent from school because of sickle cell pain. The lower rate of clinical SCC observed in the pooled active groups vs placebo did not reach statistical significance (rate ratio, 0.47; 95% CI, 0.20-1.11; P = .07). All tested doses were safe and well tolerated. This trial was registered at www.clinicaltrials.gov as #NCT02973360.

Abstract: Adenosine A2A receptor (A2AR) agonists have been shown to decrease tissue inflammation induced by hypoxia/reoxygenation in mice with sickle cell disease (SCD). The key mediator of the A2AR agonist's anti-inflammatory effects is a minor lymphocyte subset, invariant natural killer T (iNKT) cells. We tested the hypothesis that administration of an A2AR agonist in patients with SCD would decrease iNKT cell activation and dampen the severity of vaso-occlusive (VO) crises. In a phase 2, randomized, placebo-controlled trial, we administered a 48-hour infusion of the A2AR agonist regadenoson (1.44 μg/kg per hour) to patients with SCD during VO crises to produce a plasma concentration of ∼5 nM, a concentration known from prior studies to suppress iNKT cell activation in SCD. The primary outcome measure was a >30% reduction in the percentage of activated iNKT cells. Ninety-two patients with SCD were randomized to receive a 48-hour infusion of regadenoson or placebo, in addition to standard-of-care treatment, during hospital admission for a VO crisis and had analyzable iNKT cell samples. The proportion of subjects who demonstrated a reduction of >30% in activated iNKT cells was not significantly different between the regadenoson and placebo arms (43% vs 23%; P = .07). There were also no differences between regadenoson and placebo groups in length of hospital stay, mean total opioid use, or pain scores. These data demonstrate that a low-dose infusion of regadenoson intended to reduce the activity of iNKT cells is not sufficient to produce a statistically significant reduction in such activation or in measures of clinical efficacy. This trial was registered at www.clinicaltrials.gov as #NCT01788631.

Pediatric inflammatory bowel disease (PIBD) is rising rapidly in many industrialized and affluent areas in the Asia‐Pacific region. Current available guidelines, mainly from Europe and North America, may not be completely applicable to clinicians caring for children with PIBD in this region due to differences in disease characteristics and regional resources constraints. This position paper is an initiative from the Asian Pan‐Pacific Society for Pediatric Gastroenterology, Hepatology and Nutrition (APPSPGHAN) with the aim of providing an up‐to‐date, evidence‐based approach to PIBD in the Asia‐Pacific region, taking into consideration the unique disease characteristics and financial resources available in this region. A group of pediatric gastroenterologists with special interest in PIBD performed an extensive literature search covering epidemiology, disease characteristics and natural history, management, and monitoring. Gastrointestinal infections, including tuberculosis, need to be excluded before diagnosing IBD. In some populations in Asia, the Nudix Hydrolase 15 (NUD15) gene is a better predictor of leukopenia induced by azathioprine than thiopurine‐S‐methyltransferase (TPMT). The main considerations in the use of biologics in the Asia‐Pacific region are high cost, ease of access, and potential infectious risk, especially tuberculosis. This position paper provides a useful guide to clinicians in the medical management of children with PIBD in the Asia‐Pacific region. [ABSTRACT FROM AUTHOR]

Disease phenotype of pediatric inflammatory bowel disease (PIBD) in children from the Asia‐Pacific region differs from that of children from the West. Many parts of Asia are endemic for tuberculosis, making diagnosis and management of pediatric Crohn's disease a challenge. Current available guidelines, mainly from Europe and North America, may not be completely applicable to clinicians caring for children with PIBD in Asia due to differences in disease characteristics and regional resource constraints. This position paper is an initiative from the Asian Pan‐Pacific Society for Pediatric Gastroenterology, Hepatology and Nutrition (APPSPGHAN) that aims to provide an up‐to‐date, evidence‐based approach to PIBD in the Asia‐Pacific region. A group of pediatric gastroenterologists with a special interest in PIBD performed an extensive literature search covering epidemiology, disease characteristics and natural history, management, and monitoring. Attention was paid to publications from the region with special consideration to a resource‐limited setting. This current position paper deals with surgical management, disease monitoring, immunization, bone health, and nutritional issues of PIBD in Asia. A special section on differentiating pediatric Crohn's disease from tuberculosis in children is included. This position paper provides a useful guide to clinicians in the surgical management, disease monitoring, and various health issues in children with IBD in Asia‐Pacific region. [ABSTRACT FROM AUTHOR]

The high childhood mortality and life-long complications associated with sickle cell anemia (SCA) in developing countries could be significantly reduced with effective prophylaxis and education if SCA is diagnosed early in life. However, conventional laboratory methods used for diagnosing SCA remain prohibitively expensive and impractical in this setting. This study describes the clinical validation of a low-cost paper-based test for SCA that can accurately identify sickle trait carriers (HbAS) and individuals with SCA (HbSS) among adults and children over 1 year of age.In a population of healthy volunteers and SCA patients in the United States (n = 55) the test identified individuals whose blood contained any HbS (HbAS and HbSS) with 100% sensitivity and 100% specificity for both visual evaluation and automated analysis, and detected SCA (HbSS) with 93% sensitivity and 94% specificity for visual evaluation and 100% sensitivity and 97% specificity for automated analysis. In a population of post-partum women (with a previously unknown SCA status) at a primary obstetric hospital in Cabinda, Angola (n = 226) the test identified sickle cell trait carriers with 94% sensitivity and 97% specificity using visual evaluation (none of the women had SCA). Notably, our test permits instrument- and electricity-free visual diagnostics, requires minimal training to be performed, can be completed within 30 minutes, and costs about $0.07 in test-specific consumable materials.Our results validate the paper-based SCA test as a useful low-cost tool for screening adults and children for sickle trait and disease and demonstrate its practicality in resource-limited clinical settings.

Discovery and validation of genetic variants that influence disease severity in children with sickle cell anemia (SCA) could lead to early identification of high-risk patients, better screening strategies, and intervention with targeted and preventive therapy. We hypothesized that newly identified genetic risk factors for the general African American population could also impact laboratory biomarkers known to contribute to the clinical disease expression of SCA, including variants influencing the white blood cell count and the development of albuminuria and abnormal glomerular filtration rate. We first investigated candidate genetic polymorphisms in well-characterized SCA pediatric cohorts from three prospective NHLBI-supported clinical trials: HUSTLE, SWiTCH, and TWiTCH. We also performed whole exome sequencing to identify novel genetic variants, using both a discovery and a validation cohort. Among candidate genes, DARC rs2814778 polymorphism regulating Duffy antigen expression had a clear influence with significantly increased WBC and neutrophil counts, but did not affect the maximum tolerated dose of hydroxyurea therapy. The APOL1 G1 polymorphism, an identified risk factor for non-diabetic renal disease, was associated with albuminuria. Whole exome sequencing discovered several novel variants that maintained significance in the validation cohorts, including ZFHX4 polymorphisms affecting both the leukocyte and neutrophil counts, as well as AGGF1, CYP4B1, CUBN, TOR2A, PKD1L2, and CD163 variants affecting the glomerular filtration rate. The identification of robust, reliable, and reproducible genetic markers for disease severity in SCA remains elusive, but new genetic variants provide avenues for further validation and investigation.