The Prevalence of Polycystic Ovary Syndrome: A Brief Systematic Review.

BACKGROUND: Polycystic ovary syndrome (PCOS), the major endocrinopathy among reproductive-aged women, is not yet perceived as an important health problem in the world. It affects 4%-20% of women of reproductive age worldwide. The prevalence, diagnosis, etiology, management, clinical practices, psychological issues, and prevention are some of the most confusing aspects associated with PCOS. AIM: The exact prevalence figures regarding PCOS are limited and unclear. The aim of this review is to summarize comprehensively the current knowledge on the prevalence of PCOS. MATERIALS AND METHODS: Literature search was performed through PubMed, ScienceDirect, Cochrane Library, and Google Scholar (up to December 2019). All relevant articles published in English language were identified following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Our analysis yielded 27 surveys with a pooled mean prevalence of 21.27% using different diagnostic criteria. The proportion of women with PCOS also increased in the last decade. CONCLUSION: The current review summarizes and interprets the results of all published prevalence studies and highlights the burden of the syndrome, thereby supporting early identification and prevention of PCOS in order to reverse the persistent upward trend of prevalence.

Development of glycerol biosensor based on co-immobilization of enzyme nanoparticles onto graphene oxide nanoparticles decorated pencil graphite electrode.

An improved amperometric biosensor was fabricated by immobilizing glycerol kinase (GK) and glycerol-3-phosphate oxidase (GPO) nanoparticles (NPs) onto graphene oxide nanoparticles (GrONPs) modified pencil graphite (PG) electrode. The GKNPs, GPONPs and GrONPs were characterized by UV spectroscopy, and transmission electron microscopy (TEM). The working electrode (GKNPs/GPONPs/GrONPs/PGE) was characterized by scanning electron microscopy (SEM), electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) techniques. The biosensor exhibited optimal current response at an applied potential of 0.45 V, pH 8.0, and 35 °C. The biosensor displayed a wide linear response for glycerol concentration from 0.001 to 60 mM with a detection limit of 0.002 µM. Moreover, a very high sensitivity 121.45 µA·mM-1·cm-2, rapid response time (2 s) and a good concurrence with the standard enzymic colorimetric technique with a correlation coefficient (R2 = 0.99) was offered by the present biosensor. Evidently, biosensor revealed an analytical recovery of 98.5% after addition of glycerol to the sera samples. Within and between batches studies of working electrode demonstrated coefficients of variation of 0.098% and 0.101%, respectively. The biosensor measured blood serum glycerol level in patients suffering from hyperglyceridemia. The biosensor lost 25% of its initial activity after its regular use over a period of 210 days, at 4 °C storage condition.

Cholesterol biosensors: A review.

Cholesterol is the most important sterol synthesized by most of the human cells majorly in the liver. It is a necessary constituent of cell membranes, it acts as a precursor for the synthesis of steroid hormones, vitamin D, and bile acids. Cholesterol is transported in plasma primarily in the form of low-density lipoproteins (LDL), the principal route for its removal from tissues to the liver is in high-density lipoproteins (HDL), followed by excretion in the bile. Cholesterol level is less than 200 mg/dL in healthy persons. 200 and 239 mg/dL is considered borderline high and 240 mg/dL and above is considered a biomarker for cardiovascular diseases, heart attack, strokes, peripheral arterial disease, type 2 diabetes and high blood pressure. Several methods are available for detection of cholesterol, among them, most are burdensome, time-consuming, require sample pre-treatment, high-cost instrumental set-up, and experienced personnel to operate. Biosensing approach overcomes these disadvantages, as these are highly specific, fast, easy, cost-effective, and highly sensitive. The review describes the various cholesterol biosensors. Cholesterol biosensors work ideally within 1 to 300 s, in pH range, 7.0-8.6, temperature 25-37 °C and cholesterol concentration range, 0.000025-700 mM, the detection limits being in the range, 0.000002-4 mM, with working potential -0.05 to 0.65 V. These biosensors measured cholesterol level in fruit juices, beverages, sera and urine samples and reused up to 200 times over a period of 15 to 50 days, while stored dry at 4 °C (Table 1). Future perspective for further improvement and commercialization of cholesterol biosensors are discussed.

Determination of urea with special emphasis on biosensors: A review.

Urea is the major end product of nitrogen metabolism in humans, which is eliminated from the body mainly by the kidneys through urine but is also secreted in body fluids such as blood and saliva. Its level in urine ranges from 7 to 20 mg/dL, which drastically rises under patho-physiological conditions thus providing key information of renal function and diagnosis of various kidney and liver disorders. Increase in urea levels in blood, also referred to as azotemia or uremia. The chronic kidney disease (CKD) or end stage renal disease (ESRD) is generally caused due to the progressive loss of kidney function. Hence, there is an urgent need of determination of urea in biological fluids to diagnose these diseases at their early stage. Among the various methods available for detection of urea, most are complicated and require time-consuming sample pre-treatment, expensive instrumental set-up and trained persons to operate, specifically for chromatographic methods. The biosensing methods overcome these drawbacks, as these are simple, fast, specific and highly sensitive and can also be applied for detection of urea in vivo. This review presents the principles of various analytical methods for determination of urea with special emphasis on biosensors. The use of various nanostructures and electrochemical microfluidic paper based analytical device (EµPAD) are suggested for further development of urea biosensors.

Construction and application of amperometric sarcosine biosensor based on SOxNPs/AuE for determination of prostate cancer.

An improved amperometric sarcosine biosensor was constructed based on covalent immobilization of sarcosine oxidase nanoparticles (SOxNPs) onto gold electrode (AuE). The SOxNPs/AuE was characterized by scanning electron microscopy (SEM), fourier transform infrared (FTIR) spectroscopy and electrochemical impedance spectroscopy (EIS) at different stages of its construction. The biosensor worked optimally within 2 s at a potential of 1.0 V, against Ag/AgCl, pH 6.5 and 35 °C. A linear relationship was observed between sarcosine concentration range, 0.1-100 µM and the biosensor response i.e. current in mA under optimum conditions. The biosensor offered a low detection limit of 0.01 µM and gratifying storage stability. The SOxNPs/AuE was unaffected by a number of serum substances at their physiological concentrations. The biosensor measured sarcosine level in sera collected from persons suffering from prostate cancer (mean13.5 µM, n = 8), which was significantly higher (p < 0.01) than those in apparently healthy persons (mean 2.2 µM, n = 8). The SOxNPs/Au electrode was reused 300- times during the span of 180 days, with only 10% loss in its initial activity while being stored dry at 4 °C.

Biosensors for determination of D and L- amino acids: A review.

Amino acids (AAs) of nutritional importance exist as L-isomers, while D-isomeric form of AAs is common constituent of bacterial cell wall. The presence of D-amino acids in foods is promoted by harsh technological processes (e.g., high temperature, extreme pH, adulteration or microbial contamination). The detection of free AAs in different brain disorders is also very important. Among the various methods available for detection of AAs, most are complicated and require time-consuming sample pre-treatment, expensive instrumental set-up and trained persons to operate, specifically for chromatographic methods. The biosensing methods overcome these drawbacks, as these are simple, fast, specific and highly sensitive and can also be applied for detection of AAs in vivo. This review presents the principles, merits and demerits of various analytical methods for AA determination with special emphasis on D-amino acids (DAA) and L-amino acids (LAA) biosensors. The electrochemical AA biosensors work optimally within 2-900 s, pH range, 5.3-9.5; temperature range, 25-45 °C; AA concentration range, 0.0008-8000 mM, limit of detection(LOD) between 0.02 and 1250 µM and working potential from -0.05 to 0.45 V. These biosensors measured AA level in fruit juices, beverages, urine, sera and were reused 200 times over a period of 7-120 days. The use of various nanostructures and electrochemical microfluidic paper based analytical device (EµPAD) are suggested for further development of AA biosensors.

Fabrication of glycerol biosensor based on co-immobilization of enzyme nanoparticles onto pencil graphite electrode.

Glycerol kinase (GK) and glycerol-3- phosphate oxidase (GPO) nanoparticles (NPs) were prepared, characterized and immobilized onto pencil graphite (PG) electrode to fabricate an improved amperometric glycerol biosensor (GKNPs/GPONPs/PGE). GKNPs/GPONPs/PGE worked in optimum conditions of pH 7.0, temperature 30 °C, at an applied potential of -0.3 V. The biosensor exhibited wide linear response in a concentration range of glycerol (0.01-45 mM) with detection limit 0.0001 µM. The biosensor revealed high sensitivity (7.24 µAmM-1cm-2), low response time (2.5s) and a good agreement with the standard enzymic colorimetric method with a correlation coefficient (R2 = 0.99). The evaluation study of biosensor offered a good analytical recovery of 98.73% when glycerol concentration was added to the sera sample. In addition, within and between batches study of working electrode showed coefficients of variation as 0.105% and 0.14%, respectively. The application of biosensor is performed in the serum of apparently healthy subject and patients affected by cardiogenic shock. There was a 20% loss in initial activity of biosensor after its regular use over a time period of 180 days, while being stored at 4 °C.

An ultrasensitive amperometric determination of lactate by lactate dehydrogenase nanoparticles immobilized onto Au electrode.

The nanoparticles (NPs) of commercial lactate dehydrogenase (LDH) from rabbit muscle were prepared, characterized and immobilized covalently onto Au electrode to construct an improved amperometric lactate biosensor. The biosensor showed optimum response within 2.5 s at an applied potential of 0.10 V, pH 7.0 and 35 °C. The biosensor had a wider working range linear (0.01 µM to 55 mM) with a higher sensitivity (3.45 ±â€¯0.02 µA cm-2 mM-1) and a lower detection limit (0.01 µM) compared to earlier biosensors. The analytical recovery of added lactate in sera was 98.61% and within and between batches coefficients of variations (CVs) were 1.38% and 1.03%, respectively. A good correlation coefficient (R2 = 0.99) was observed between sera lactate values as measured by the standard enzymatic colorimetric method and the present biosensor. The biosensor measured lactic acid in the sera of apparently healthy subjects and persons suffering from cardiogenic shocks. There was a 10% loss in the initial activity of LDHNPs/Au electrode after its regular use over a period of 210 days, while being stored dry at 4 °C.

Fabrication of an amperometric sarcosine biosensor based on sarcosine oxidase/chitosan/CuNPs/c-MWCNT/Au electrode for detection of prostate cancer.

An amperometric sarcosine biosensor was fabricated based on covalent immobilization of sarcosine oxidase (SarOx) onto the nanocomposite of carboxylated multi-walled carbon nanotubes (cMWCNT)/chitosan (CHIT) and copper nanoparticles (CuNPs), electrodeposited on gold (Au) electrode. The SarOx/CHIT/CuNPs/c-MWCNT/Au electrode was characterized by scanning electron microscopy (SEM), electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). The enzyme electrode exhibited optimum current within 2 s at a potential of 0.2 V against Ag/AgCl, pH 7.0 and 35 °C. A linear relationship was obtained between sarcosine concentration in the range, 0.1-100 µM and current (mA) under optimum conditions. The biosensor exhibited a high sensitivity of 277.5 µA/µM/cm2, a low detection limit of 0.1 pM and excellent storage stability (180 days). The analytical recoveries of added sarcosine in sera at 0.5 µM and at 1.0 µM concentration were 95.5% and 97.30 respectively. The precision i.e. within and between-batch coefficients of variation (CVs) were 1.08% and 1.70% respectively. There was a good correlation (R2 = 0.99) between the level of sarcosine in sera as measured by the standard immuno kit method and the present biosensor. The biosensor measured sarcosine level in sera of prostate cancer patients, which was significantly higher than those of apparently healthy persons (p value <0.01).

Quantitative analysis of hydrogen peroxide with special emphasis on biosensors.

Determination of hydrogen peroxide (H2O2) has become essential in pharmaceutical, biological, clinical and environmental studies. The conventional detection methods of H2O2 such as colourimetry, titration, chromatography, spectrophotometry, fluorimetry, chemiluminescence have limited success, due to their poor selectivity and sensitivity, long analysis time and lack of long-term reliability and reproducibility. The biosensors overcome these limitations because of their simplicity, rapidity, selectivity and high sensitivity. This review describes the principle, analytic parameters, merits and demerits of various methods of H2O2 determination with special emphasis on biosensors. The classification of biosensors based on various materials/nanomaterials and electrodes have been described in detail. The recent advances in vivo sensing and bio-sensing of H2O2 by hemoglobin nanoparticles are also presented. The significant challenges and future perspective for highly selective H2O2 detection are discussed.

Biosensing methods for determination of triglycerides: A review.

Triglycerides (TGs) are the major transporters of dietary fats throughout the bloodstream. Besides transporting fat, TGs also act as stored fat in adipose tissue, which is utilized during insufficient carbohydrates supply. TG level is below 150mg/dL in healthy persons. Elevated TGs level in blood over 500mg/dL is a biomarker for cardiovascular diseases, Alzheimer disease, pancreatitis and diabetes. Numerous methods are accessible for recognition of TGs, among them, most are cumbersome, time-consuming, require sample pre-treatment, high cost instrumental set-up and experienced personnel to operate. Biosensing approach overcomes these disadvantages, as these are highly specific, fast, easy, cost effective, and highly sensitive. This review article describes the classification, operating principles, merits and demerits of TG biosensors, specifically nanomaterials based biosensors. TG biosensors work ideally within 2.5-2700s, in pH range, 6.0-11.0, temperature 25-39.5°C and TG concentration range, 0.001-100mM, the detection limits being in the range, 0.1nM to 0.56mM, with working potential - 0.02 to 1.2V. These biosensors measured TG level in fruit juices, beverages, sera and urine samples and reused upto 200 times over a period of 7-240 days, while stored dry at 4°C. Future perspective for further improvement and commercialization of TG biosensors are discussed.

An amperometric H2O2 biosensor based on hemoglobin nanoparticles immobilized on to a gold electrode.

The nanoparticles (NPs) of hemoglobin (Hb) were prepared by desolvation method and characterized by transmission electron microscopy (TEM), UV spectroscopy and Fourier-transform IR (FTIR) spectroscopy. An amperometric H2O2 biosensor was constructed by immobilizing HbNPs covalently on to a polycrystalline Au electrode (AuE). HbNPs/AuE were characterized by scanning electron microscopy (SEM), cyclic voltammetry (CV) and electrochemical impedance spectra (EIS) before and after immobilization of HbNPs. The HbNPs/AuE showed optimum response within 2.5 s at pH 6.5 in 0.1 M sodium phosphate buffer (PB) containing 100 µM H2O2 at 30°C, when operated at -0.2 V against Ag/AgCl. The HbNPs/AuE exhibited Vmax of 5.161 ± 0.1 µA cm-2 with apparent Michaelis-Menten constant (Km) of 0.1 ± 0.01 mM. The biosensor showed lower detection limit (1.0 µM), high sensitivity (129 ± 0.25 µA cm-2 mM-1) and wider linear range (1.0-1200 µM) for H2O2 as compared with earlier biosensors. The analytical recoveries of added H2O2 in serum (0.5 and 1.0 µM) were 97.77 and 98.01% respectively, within and between batch coefficients of variation (CV) were 3.16 and 3.36% respectively. There was a good correlation between sera H2O2 values obtained by standard enzymic colorimetric method and the present biosensor (correlation coefficient, R2 =0.99). The biosensor measured H2O2 level in sera of apparently healthy subjects and persons suffering from diabetes type II. The HbNPs/AuE lost 10% of its initial activity after 90 days of regular use, when stored dry at 4°C.

An improved amperometric triglyceride biosensor based on co-immobilization of nanoparticles of lipase, glycerol kinase and glycerol 3-phosphate oxidase onto pencil graphite electrode.

Nanoparticles (NPs) of commercial lipase from Candida rugosa, of glycerol kinase (GK) from Cellulomonas species, of glycerol-3- phosphate oxidase (GPO) from Aerococcus viridans were prepared, characterized and co-immobilized onto a pencil graphite (PG) electrode. The morphological and electrochemical characterization of PG electrode was performed by scanning electron microscopy (SEM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) before and after co-immobilization of enzyme nanoparticles (ENPs). An improved amperometric triglyceride (TG) biosensor was fabricated using Lipase NPs/GKNPs/GPONPs/PG electrode as the working electrode, Ag/AgCl as the standard electrode and Pt wire as auxiliary electrode. The biosensor showed optimum response within 2.5s at a pH 7.0 and temperature of 35°C. The biosensor measured current due to electrons generated at 0.1V against Ag/AgCl, from H2O2, which is produced from triolein by co-immobilized ENPs. A linear relationship was obtained over between a wide triolein concentration range (0.1mM-45mM) and current (mA) under optimal conditions. The Lipase NPs/GKNPs/GPONPs/PG electrode showed high sensitivity (1241±20mAcm-2mM-1); a lower detection limit (0.1nM) and good correlation coeficient (R2=0.99) with a standard enzymic colorimetric method. Analytical recovery of added triolein in serum was 98.01%, within and between batch coefficients of variation (CV) were 0.05% and 0.06% respectively. The biosensor was evaluated and employed for determination of TG in the serum of apparently healthy subject and persons suffering from hypertriglyceridemia. The biosensor lost 20% of its initial activity after its continued uses over a period of 240days, while being stored at 4°C.

Determination of lactic acid with special emphasis on biosensing methods: A review.

Lactic acid (2-Hydroxypropanoic acid) is generated from pyruvic acid under anaerobic condition in skeletal muscles, brain, red blood cells, and kidney. Lactate in normal human subjects get cleared very quickly at a rate of 320mmol/L/hr, mostly by liver metabolism and re-conversion of lactate back to pyruvate. Measurement of lactate level in serum is required for the differential diagnosis and medical management of hyperlactatemia, cardiac arrest and resuscitation, sepsis, reduced renal excretion, hypoxia induced cancer, decreased extra hepatic metabolism, intestinal infarction and lactic acidosis. Determination of lactate is also important in dairy products and beverages to access their quality. Among the various methods available for detection of lactate, most are complicated, nonspecific, less sensitive and require time-consuming sample pretreatment, expensive instrumental set-up and trained persons to operate, specifically for chromatographic methods. Biosensing methods overcome these drawbacks, as these are simple, fast, specific and highly sensitive. Lactate biosensors reported so far, work optimally within 3-180s, between pH, 5.5-8.5 and temperature 22°C to 37°C and lactate concentration ranging from 10 to 2000µM. These biosensors have been employed to measure lactate level in embryonic cell culture, beverages, urine, and serum samples and reused upto 200-times within a period of 7-216 days. This review presents the principles, merits and demerits of various analytical methods for lactate determination with special emphasis on lactate biosensors. The future perspective for improvement of analytic performance of lactate biosensors are discussed.