High prevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibodies among unvaccinated children of Chandigarh, Northwest India, in a household-based paediatric serosurvey post-second wave of pandemic (June to July 2021).

OBJECTIVE: Current national severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination policy covers children aged >12 years. Unvaccinated, uninfected children remain susceptible to SARS-CoV-2 and play a role in community transmission, as paediatric infection is mostly mild or asymptomatic. To estimate the proportion of susceptible children in a community for public health measures, there is a need to assess the extent of natural infection. STUDY DESIGN: We performed a cross-sectional household serosurvey of SARS-CoV-2 antibodies in unvaccinated children aged between 6 and 18 years after the second COVID-19 wave. METHODS: Anti-SARS-CoV-2 immunoglobin G (IgG) testing in serum was done using chemiluminescence immunoassay. We used a logistic regression model to investigate predicted factors of seropositivity. RESULTS: We observed a high prevalence (weighted average: 68.3%) of anti-SARS-CoV-2 IgG in 2700 enrolled children. Logistic regression for predictors of IgG seropositivity showed lower odds in households with completely vaccinated adults (adjusted odds ratio [OR]: 0.43, 95% confidence interval [CI]: 0.26-0.71, P = 0.0011) compared with households with unvaccinated adults. Other factors for low seropositivity included frontline workers as family members (adjusted OR: 0.69, 95% CI: 0.52-0.91, P = 0.0091) and non-crowded households (adjusted OR: 0.74, 95% CI: 0.61-0.89, P = 0.0019). CONCLUSION: A high SARS-CoV-2 IgG prevalence in unvaccinated children was indicative of previous exposure to potentially infected contacts. This implies in-person academic activities for children can be continued during future community transmission. Comparatively lower seropositivity in children of completely vaccinated households or frontline workers suggests decreased transmission due to vaccination-induced immunity of family members. Vaccination will still be required in these children to maintain protective IgG levels, particularly in low seroprevalence groups.

Computational-sampling-moiré-based on-machine alignment for freeform optics.

The manufacturing and characterization of freeform optical surfaces are influenced by their high sensitivity to misalignments. In this work, the computational sampling moiré technique combined with phase extraction is developed for the precise alignment of freeform optics during fabrication and in metrology applications. This novel, to the best of our knowledge, technique achieves near-interferometry-level precision in a simple and compact configuration. This robust technology can be applied to industrial manufacturing platforms (such as diamond turning machines, lithography, and other micro-nano-machining techniques) as well as their metrology equipment. In a demonstration of computational data processing and precision alignment using this method, iterative manufacturing of freeform optical surfaces with a final-form accuracy of about 180 nm was accomplished.

Evaluation of Pleurotus Mushroom Effects on Histopathological Changes in Organs of Diabetic Rats.

Diabetes mellitus (DM) is a metabolic disorder that can be categorized mainly into type 1 and type 2. Diabetes type 1 is caused due to ß-cell destruction, whereas type 2 is caused by the resistance of cell receptors. Many therapies are available for the management of diabetes, but they have some side effects, and as a result of this, people are attracted to natural treatments. Pleurotus mushrooms are well documented for their medicinal attributes and their role in the treatment of diseases like cancer, infectious disease, neurodiseases, and inflammatory disease. The protective mechanism of the Pleurotus fossulatus (P. fossulatus) mushroom and its detailed histological study on kidneys and the liver in diabetic conditions were unexplored. The present study evaluated the effects of P. fossulatus aqueous extract on histological changes in the diabetic rat model. Male Wistar albino rats were used to create the diabetic model by using streptozotocin (STZ) intraperitoneal (IP) injection. The animals were separated into five different groups, with six animals in each. Only group I, animals that did not receive STZ, was considered a normal control. Group II was a diabetic control and received normal saline, and group III was a drug control and received metformin as a standard drug. Groups IV and V were dosing groups, which received the aqueous extract of P. fossulatus in 250 mg/kg and 500 mg/kg of body weight concentrations, labeled as T1 and T2 groups, respectively. The T1 and T2 groups clearly showed their potential to reverse the histopathological changes in the kidney and liver. However, the T2 group was more effective than the T1 group, as results indicate that functions of the glomerulus and its structural deformity were restored to their near-natural form in the T2 group. In the case of the liver, the histological changes like the dilatation of sinusoids, more numbers of the Kupffer cell formation, and necrosis were restored in the T2 group. All these results proved the potential of P. fossulatus against the side effects of diabetes. It could protect the organs from developing diabetic nephropathy (DN) and liver-related diseases like cirrhosis and nonalcoholic fatty liver disease (NAFLD).

Beta glucan as an immune stimulant in tumor microenvironment - Insight into lessons and promises from past decade.

Cancer is characterized by a perturbed immune landscape. Inside tumor microenvironment, immune system is reprogrammed to facilitate tumor growth and survival rather than eliminating it. This immune evasive mechanism needs to be reversed to normal for effective anticancer therapeutic strategy. Immunotherapy has emerged as a novel strategy for redeployment of immune cells against cancer. However, they suffer in their efficacy, response rate and side effects. This necessitated us to turn toward natural repertoires which can act as a substitute to conventional immunotherapeutics. Beta glucan, a polysaccharide derived from mushroom, serves the role of immunomodulator inside tumor microenvironment. It acts as pathogen associated molecular pattern and bind to various pattern recognition receptors expressed on surface of immune cells thereby facilitating their activation and crosstalk. This result in resurgence of suppressed immune surveillance in the tumor milieu. In this review, we highlight in brief the advances and limitation of cancer immunotherapy. Alongside, we have discussed the detailed mechanistic principle and recent advances underlying restoration of immune functionality by beta glucan.

Prognostic significance of soft tissue deposits in head and neck squamous cell carcinoma: a systematic review and meta-analysis.

Soft tissue deposits, also known as tumour deposits (TDs), have not been studied well in head and neck squamous cell carcinoma (HNSCC) and are not included in any of the staging systems or treatment guidelines. The aim of this systematic review was to determine the prevalence and prognostic implications of TDs in patients with HNSCC. This systematic review of the literature was conducted following the PRISMA guidelines. The PubMed, Embase, and Scopus electronic databases were searched for relevant studies, from inception to August 2022. Although 14 studies qualified for inclusion, only eight were finally included in the review due to the considerable overlap of patients in several studies. Data from 7127 patients were analysed. The pooled prevalence of TDs was 21% (95% confidence interval (CI) 9-33%). The presence of TDs was adversely associated with overall survival and disease-free survival, with hazard ratios of 2.08 (95% CI 1.60-2.70) and 2.56 (95% CI 1.97-3.32), respectively. TDs are detected in a significant number of patients with HNSCC and adversely affect survival. Longitudinal prospective studies are needed to evaluate the prognostic implications of TDs in HNSCC for their potential role in cancer staging and adjuvant treatment planning.

Prevalence of Asymptomatic Bacteriuria and Antimicrobial Resistance Profile among Pregnant Females in a Tertiary Care Hospital.

BACKGROUND AND OBJECTIVES: Urinary tract infection (UTI) is the most common clinical finding during pregnancy, and if it is asymptomatic bacteriuria (ASB), it can progress to pyelonephritis, leading to further complications. The present study aims to know the prevalence of ASB in pregnant females and the antimicrobial resistance pattern in our hospital setup. MATERIALS AND METHODS: A total of 552 urine samples were collected from pregnant females (with no symptoms of UTI) both attending outpatient department and admitted in the wards of obstetrics and gynecology department. Urine culture was performed on blood agar, MacConkey agar, and UTI chromogenic agar. Antibiotic sensitivity test was done using Kirby-Bauer disc diffusion method, and the results were interpreted. RESULTS: The prevalence rate of ASB in pregnant females was 17.4%. It was common in the age group of 25-33 years (60.4%). The infection rate was higher in the second trimester (43.7%) compared to the third (29.2%) and first (27.1%) trimester. Multiparity (60.4%) was a common finding in ASB during pregnancy. There was a significant finding of previous history of UTI (22.9%) and anemia (58.3%) associated with ASB in pregnant females. Escherichia coli (39.2%) was the most common microorganism isolated followed by Staphylococcus aureus (34.3%), Enterococcus faecalis (14.7%), Klebsiella (4.9%), coagulase-negative Staphylococcus spp. (2.9%), and Citrobacter and Acinetobacter (1.9%). Most sensitive drugs to be given in ASB during pregnancy were nitrofurantoin and fosfomycin. CONCLUSION: It was emphasized that urine culture should be done in early antenatal visit as routine screening to identify ASB in pregnant females as it can prevent fetal and maternal complications.

Therapeutic Potential of Phytoconstituents in Management of Alzheimer's Disease.

Since primitive times, herbs have been extensively used in conventional remedies for boosting cognitive impairment and age-associated memory loss. It is mentioned that medicinal plants have a variety of dynamic components, and they have become a prominent choice for synthetic medications for the care of cognitive and associated disorders. Herbal remedies have played a major role in the progression of medicine, and many advanced drugs have already been developed. Many studies have endorsed practicing herbal remedies with phytoconstituents, for healing Alzheimer's disease (AD). All the information in this article was collated from selected research papers from online scientific databases, such as PubMed, Web of Science, and Scopus. The aim of this article is to convey the potential of herbal remedies for the prospect management of Alzheimer's and related diseases. Herbal remedies may be useful in the discovery and advancement of drugs, thus extending new leads for neurodegenerative diseases such as AD. Nanocarriers play a significant role in delivering herbal medicaments to a specific target. Therefore, many drugs have been described for the management of age-linked complaints such as dementia, AD, and the like. Several phytochemicals are capable of managing AD, but their therapeutic claims are restricted due to their lower solubility and metabolism. These limitations of natural therapeutics can be overcome by using a targeted nanocarrier system. This article will provide the primitive remedies as well as the development of herbal remedies for AD management.

Promising anticancer activity of polysaccharides and other macromolecules derived from oyster mushroom (Pleurotus sp.): An updated review.

Cancer dominates among many causes of mortality worldwide. Traditional chemotherapeutic agents are powerful anti-cancer agents employed for treatment of this deadly disease. However, they are always associated with toxic side effects and immunosuppression making person more vulnerable to tumor relapse and fatalities. A promising alternative could be identification, isolation and transfer of naturally occurring bioactive macromolecules to the tumorigenic population. Oyster mushroom, a major source of nutraceuticals, belonging to class basidiomycetes of kingdom Mycota is known to have immense therapeutic properties. It is a reservoir of macromolecules like ß-glucan, α-glucan, resveratrol, concanavalin A, cibacron blue affinity protein, p-hydroxybenzoic acid, ergosterol, linoleic acid etc. that are responsible for mediating anti-tumor, immunomodulatory, antioxidant, and anti-diabetic roles. Various studies have shown that extracts derived from oyster mushroom is rich in polysaccharides like ß-glucan and other macro molecules which have an anti-proliferative effect against cancer cell lines, without harming the normal cells. This review presents a brief highlight of the work covering the overall significance of oyster mushroom in different types of cancer treatment. It also explores the immunomodulatory effects of polysaccharides, proteoglycans and polypeptides derived from oyster mushroom that boosts the immune system to overcome the limitation of traditional cancer therapies.

Silicon Interpositional Arthroplasty for Temporo-mandibular Joint Ankylosis.

Temporo-mandibular joint (TMJ) ankylosis is characterized by a decreased mouth opening which affects mastication, speech, and facial aesthetic. Interpositional arthroplasty using autologous tissue is accepted treatment for TMJ Ankylosis; however, harvesting autologous tissue is associated with additional morbidity. In this article we report our results of silicon interpositional arthroplasty for TMJ ankylosis. 20 patients with TMJ ankylosis were included in the study. All patients underwent standard operative procedure using preauricular incision for release of TMJ ankylosis by excision of at least 1 cm of bony block and insertion of 2 cm thick silicon block in the joint space. Postoperatively early mobilization of TMJ was advised from 3rd day onwards. Post operative result was evaluated by assessing the mouth opening as inter incisor distance (IID). 20 patients (27 joints) of TMJ ankylosis were included in the study. There were 8 male and 12 female patients with age ranged from 3-35 years. According to Sawhney classification bony ankylosis was present as Type-IV (n = 13 joints), Type-III (n = 12 joints) and Type-II (2 joints). Preoperative mean IID was 7.15 mm and post operative mean IID was 43.5. There was no facial nerve paresis, malocclusion or recurrence but infection and extrusion of implant occurred in 1 case each. Silicon interpositional arthroplasty is an effective procedure for the treatment of TMJ Ankylosis; as it restores mouth opening and function, maintains the vertical ramus height, and prevents re-ankylosis without any donor site morbidity.

Therapeutic applications of mushrooms and their biomolecules along with a glimpse of in silico approach in neurodegenerative diseases.

Neurodegenerative diseases (NDs) represent a common neurological pathology that determines a progressive deterioration of the brain or the nervous system. For treating NDs, comprehensive and alternative medicines have attracted scientific researchers' attention recently. Edible mushrooms are essential for preventing several age-based neuronal dysfunctions such as Parkinson's and Alzheimer's diseases. Mushroom such as Grifola frondosa, Lignosus rhinocerotis, Hericium erinaceus, may improve cognitive functions. It has also been reported that edible mushrooms (basidiocarps/mycelia extracts or isolated bioactive compounds) may reduce beta-amyloid-induced neurotoxicity. Medicinal mushrooms are being used for novel and natural compounds that help modulate immune responses and possess anti-cancer, anti-microbial, and anti-oxidant properties. Compounds such as polyphenols, terpenoids, alkaloids, sesquiterpenes, polysaccharides, and metal chelating agents are validated in different ND treatments. This review aims to assess mushrooms' role and their biomolecules utilization for treating different kinds of NDs. The action mechanisms, presented here, including reducing oxidative stress, neuroinflammation, and modulation of acetylcholinesterase activity, protecting neurons or stimulation, and regulating neurotrophins synthesis. We also provide background about neurodegenerative diseases and in-silico techniques of the drug research. High costs associated with experiments and current ethical law imply efficient alternatives with limited cost value. In silico approaches provide an alternative method with low cost that has been successfully implemented to cure ND disorders in recent days. We also describe the applications of computational procedures such as molecular docking, virtual high-throughput screening, molecular dynamic (MD) simulation, quantum-mechanical methods for drug design. They were reported against various targets in NDs.

Krüppel-like factor 1 (KLF1) gene single nucleotide polymorphisms in sickle cell disease and its association with disease-related morbidities.

Sickle cell disease has varied clinical symptoms, and patients having high fetal hemoglobin (HbF) have milder symptoms. Various genetic factors are known to modulate the HbF levels. Krüppel-like factor 1 (KLF1) is a transcription factor that regulates the beta-like globin gene expression. Any variation in KLF1 gene may alter the sickle cell disease phenotype. Xmn-I polymorphism is also known to regulate the gamma globin gene expression. Present studies were carried out to investigate the effect of KLF1 gene mutations and Xmn-I polymorphism on the sickle cell disease severity and to ascertain the genotype-phenotype correlation. One hundred and eighteen sickle cell disease patients having a median follow-up of 5 years (3-10 years) were recruited. Clinical details were recorded from their retrospective medical records. Xmn-I polymorphism were analyzed using PCR-RFLP method. Variations in KLF1 gene were identified using Sanger sequencing. Out of 118 patients, 24 had acute chest syndrome and 21 patients had more than 2 pain episodes per year. There were no significant differences in sickle cell disease-related morbidities in male and females barring leg ulcers. A total of 6 polymorphism were observed in KLF1 gene, out of which 3 are novel (c.-304G > C, c.*141A > G and c.*178A > G). No statistically significant association of any of SNPs identified in KLF1 gene or Xmn-I polymorphism was seen with HbF levels as well as the sickle cell disease-related morbidities. No association exists between fetal hemoglobin or sickle cell disease-related morbidities and Xmn-I polymorphism or with SNPs identified in KLF1 gene in the studied cohort.

Promising drug targets and associated therapeutic interventions in Parkinson's disease.

Parkinson's disease (PD) is one of the most debilitating brain diseases. Despite the availability of symptomatic treatments, response towards the health of PD patients remains scarce. To fulfil the medical needs of the PD patients, an efficacious and etiological treatment is required. In this review, we have compiled the information covering limitations of current therapeutic options in PD, novel drug targets for PD, and finally, the role of some critical beneficial natural products to control the progression of PD.

SARS-CoV-2 Detection in Gingival Crevicular Fluid.

Understanding the pathophysiology of the coronavirus disease 2019 (COVID-19) infection remains a significant challenge of our times. The gingival crevicular fluid being representative of systemic status and having a proven track record of detecting viruses and biomarkers forms a logical basis for evaluating the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The study aimed to assess gingival crevicular fluid (GCF) for evidence of SARS-CoV-2 in 33 patients who were deemed to be COVID-19 positive upon nasopharyngeal sampling. An attempt was also made to comparatively evaluate it with saliva in terms of its sensitivity, as a diagnostic fluid for SARS-CoV-2. GCF and saliva samples were collected from 33 COVID-19-confirmed patients. Total RNA was extracted using NucliSENS easyMAG (bioMérieux) and eluted in the elution buffer. Envelope gene (E gene) of SARS-CoV-2 and human RNase P gene as internal control were detected in GCF samples by using the TRUPCR SARS-CoV-2 RT qPCR kit V-2.0 (I) in an Applied Biosystems 7500 real-time machine. A significant majority of both asymptomatic and mildly symptomatic patients exhibited the presence of the novel coronavirus in their GCF samples. Considering the presence of SARS-CoV-2 RNA in the nasopharyngeal swab sampling as gold standard, the sensitivity of GCF and saliva, respectively, was 63.64% (confidence interval [CI], 45.1% to 79.60%) and 64.52% (CI, 45.37% to 80.77%). GCF was found to be comparable to saliva in terms of its sensitivity to detect SARS-CoV-2. Saliva samples tested positive in 3 of the 12 patients whose GCF tested negative, and likewise GCF tested positive for 2 of the 11 patients whose saliva tested negative on real-time reverse transcription polymerase chain reaction. The results establish GCF as a possible mode of transmission of SARS-CoV-2, which is the first such report in the literature, and also provide the first quantifiable evidence pointing toward a link between the COVID-19 infection and oral health.

Mucuna pruriens in Parkinson's and in some other diseases: recent advancement and future prospective.

Mucuna pruriens (Mp) is an annual and perennial legume which belongs to the family Fabaceae having different types of therapeutic activity. Anti-oxidative, anti-inflammatory, anti-epileptic, anti-microbial, etc. are the example of some most common activities of Mp. It is widely utilized as a potent aphrodisiac. The anti-Parkinsonian activity of Mp was explored since the nineteenth century. The neuroprotective activity of Mp was shown by several researchers. Levodopa (L-DOPA) is the important constituents responsible for the anti-Parkinsonian activity of Mp. Apart from L-DOPA, several other important bioactive components like Ursolic acid (UA) and Betulinic acid (BA) also exhibit a similar neuroprotective activity. Parkinson's disease (PD) is mainly sporadic. A very small proportion shows the genetic nature of PD. The anti-Parkinsonian activity of Mp was explored in different toxin-induced PD models as like MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), Rotenone, Paraquat, 6-hydroxydopamine (6-OHDA) as suggested by several pieces of literature. Various parts of Mp's like seed, leaf, and stem exhibit potent neuroprotective attributes. Among different parts, seeds are widely utilized as anti-PD agents because of the higher percentage of L-DOPA. Besides anti-PD activity, Mp's neuroprotective potential was also explored in the ischemic model of stroke that also shows positive results. Recently, several clinical trials have been performed on the anti-PD activity of Mp on PD patients that show convincing results. Although, a small population-based study needs to be further validated in the broader population. Apart from anti-PD activity, Mp also shows its therapeutic activity in some other diseases like cancer, diabetes, skin infection, anemia, antihypertensive, etc. that are summarized in Table 1. In this review, we have discussed the anti-PD potential of Mp in the sporadic and genetic model along with some clinical trials that have performed on PD patients. Some other activity of Mp is also summarized in this review. There is a strong need to test the efficacy of Mp in some other neurodegenerative diseases along with PD. Following this, this review emphasizes the role of Mp in PD systematically through literature analysis available to date. [Table: see text].

Prevalence and spectrum of mutations causing G6PD deficiency in Indian populations.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common human erythroenzymopathy affecting around 10% of the world population. India is endemic for malaria and antimalarial drugs are known to induce haemolysis in G6PD deficient individuals. Here we report the prevalence as well as the molecular diversity of G6PD deficiency in geographical regions of India. METHODS AND RESULTS: A total of 20,896 individuals (11,838 males and 9058 females) were screened by DPIP dye decolorisation method followed by quantitation of G6PD enzyme activity on the suspected samples. Molecular analysis was undertaken in a total of 350 G6PD deficient individuals by PCR-RFLP and DNA sequencing. A structural characteristic of the novel variant was deduced by using DynaMut web-server. The prevalence rate of G6PD deficiency varied between 0.8 and 6.3% with an overall prevalence of 1.9%. A total of twelve mutations were identified. Of the total deleterious alleles detected G6PD Orissa (56.5%) was found to be the most predominant variant followed by G6PD Mediterranean (23.6%). G6PD Mediterranean, G6PD Kaiping and G6PD Mahidol were found to be severely deficient variant and 14.1% of them showed undetectable activity. A novel mutation c.544C➔G (R182G) in exon 6 was identified in one tribal male where substitution of arginine by glycine, likely causes the alteration in the alpha helix leading to disruption of secondary structure of the protein. CONCLUSION: There are large differences in the distribution of G6PD causal variants between Indian states, and this may have implications for the treatment in the malaria endemic areas.

An overview of COVID-19 with an emphasis on computational approach for its preventive intervention.

SARS-CoV-2, a novel Betacoronavirus, has attracted global attention because of its extremely high infection rate and large number of human deaths. It possesses a positive-sense, single-stranded RNA of ~ 30 kb nucleotides as its genetic material. It is responsible for COVID-19 which has been declared a pandemic by WHO. Having reported for the first time in Wuhan, China, the virus infected over 21.48 million people and caused over 0.77 million deaths till mid-august 2020. SARS-CoV-2 contains the spike protein site that gets activated by an enzyme furin which is found in the lung, liver, and small intestine of humans. It shows the potentiality of virus for attacking multiple organs and their failures. Due to the absence of vaccines, the cure is restricted to supportive care including repurposed drugs. In silico approaches may offer an alternative screening to optimize hits to lead stages. It can provide important related to drug resistance, their lineages and evolution. This approach may also help to find an effective vaccine against COVID-19. This review focuses on the in silico aspects of genomics, proteomics, pathogenesis, phylogenetic analysis and viral receptor binding analysis in Betacoronavirus.

Pleurotus sajor-caju-Mediated Synthesis of Silver and Gold Nanoparticles Active against Colon Cancer Cell Lines: A New Era of Herbonanoceutics.

Herbal medicines are widely used worldwide and much appreciated because of their fewer side effects and the ability to fight diseases at the root cause. Active 'phyto' ingredients require a scientific approach and a mechanism to distribute components at the target site for better therapeutic results. Nanotechnology, on the other hand, has created new hope for cancer treatment but is still far from being proven in clinical settings. This article combines a unique approach to synthesis with the use of Pleurotus sajor-caju, followed by microwave irritation of silver and gold nanoparticles that ensures the capping of the active phyto ingredient and further enhances the effects of nanomedicine to fight colon cancer, thus opening a new era of what we call herbonanoceutics. The article also compares the characteristics and properties of silver (Au) and gold (Ag) nanoparticles synthesized by an in house developed novel microwave-assisted rapid green synthesis method. The as-prepared Ag NPs and Au NPs were compared using ultraviolet-visible spectroscopy (UV-Vis), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), and energy dispersive spectroscopy (EDS). Our comparative study revealed that both assemblies display face-centred cubic structures (FCCs) and are nanocrystalline in nature. The advantage of the approach was that the sizes of gold and silver were identical in range with a similar distribution pattern. This has helped us to study the activity against colon cancer cell line (HCT-116) without incoherence since size plays a key role in the application. More specifically, morphological changes, cell viability, the production of reactive oxygen species (ROS) and the fragmentation of DNA have been further reported to assess better the results obtained with the two metals. Our results suggest that the newly adopted synthesis method may ensure the dual benefits from phyto ingredients which further enhances the effectiveness of advanced nanomedicine.

Mitochondrial Dysfunction: a Potential Therapeutic Target to Treat Alzheimer's Disease.

Mitochondrial dysfunction plays a very vital role in the pathogenesis of Alzheimer's disease (AD). Several shreds of evidence have indicated that the mitochondrial function is severely compromised under AD pathogenesis. Most of the recent therapeutic strategies have been conversed to treat AD by pinpointing the pathways involved in the pathophysiology of AD. In AD, mitochondria progressively lose their proper functions that are ultimately responsible for their accumulation and removal via the autophagic process, which is called mitophagy that further worsens the progression of this incapacitating disease. Preclinical and clinical studies have suggested that mitochondrial dysfunction along with mitophagy significantly contributes to the accumulation of amyloid-beta (Aß) fibrils and hyperphosphorylated tau protein tangles which lead to synaptic dysfunctions and cognitive impairments such as memory loss through reactive oxygen species (ROS)-mediated pathway. The present review is intended to discuss the recent advancements in the frontiers of mitochondrial dysfunction and consequent therapeutic strategies that have been employed to treat AD.

Differential Iron Status and Trafficking in Blood and Placenta of Anemic and Non-anemic Primigravida Supplemented with Daily and Weekly Iron Folic Acid Tablets.

ABSTRACT: The molecular mechanism of iron transfer across placenta in response to maternal anemic status/ iron supplementation is not clear. We hypothesized that maternal iron/ anemia status during early trimesters can be utilized as a biomarker tool to get estimates of placental iron status. Early interventions can be envisaged to maintain optimum placental/ foetal iron levels for healthy pregnancy outcomes. One hundred twenty primigravida were recruited and divided into non-anemic and anemic group on the basis of hemoglobin levels. The groups were randomly allocated to receive daily and weekly iron folic acid (IFA) tablets till six weeks postpartum. Hematological and iron status markers in blood and placenta were studied along with the delivery notes. Weekly IFA supplementation in anemic primigravidas resulted in significantly reduced levels of hematological markers (p < 0.01); whereas non-anemic primigravidas showed lower ferritin and iron levels, and higher soluble transferrin receptor levels (p < 0.05). At baseline, C-reactive protein and cortisol hormone levels were also significantly lower in non-anemic primigravidas (p < 0.05). A significantly decreased placental ferritin expression (p < 0.05); and an increased placental transferrin expression was seen in anemic primigravidas supplemented with weekly IFA tablets. A significant positive correlation was observed between serum and placental ferritin expression in anemic pregnant women (r = 0.80; p < 0.007). Infant weight, gestational length and placental weight were comparable in both the supplementation groups. To conclude, mother's serum iron / anemia status switches the modulation in placental iron transporter expression for delivering the optimum iron to the foetus for healthy pregnancy outcomes. TRIAL REGISTRATION: Clinical Trial Registry-India: CTRI/2014/10/005135.