BRAF and RET polymorphism association with thyroid cancer risk, a preliminary study from Khyber Pakhtunkhwa population.

BACKGROUND: Thyroid cancer, originating in the neck's thyroid gland, encompasses various types. Genetic mutations, particularly in BRAF and RET genes are crucial in its development. This study investigates the association between BRAF (rs113488022) and RET (rs77709286) polymorphisms and thyroid cancer risk in the Khyber Pakhtunkhwa (KP) population. METHODS: Blood samples from 100 thyroid cancer patients and 100 healthy controls were genotyped using ARMS-PCR followed by gel electrophoresis and statistical analysis. RESULTS: Analysis revealed a significant association between the minor allele T of BRAF (rs113488022) and thyroid cancer risk (P = 0.0001). Both genotypes of BRAF (rs113488022) showed significant associations with thyroid cancer risk (AT; P = 0.0012 and TT; P = 0.045). Conversely, the minor allele G of RET (rs77709286) exhibited a non-significant association with thyroid cancer risk (P = 0.2614), and neither genotype showed significant associations (CG; P = 0.317, GG; P = 0.651). Demographic and clinical parameters analysis using SPSS showed a non-significant association between BRAF and RET variants and age group (P = 0.878 and P = 0.536), gender (P = 0.587 and P = 0.21), tumor size (P = 0.796 and P = 0.765), or tumor localization (P = 0.689 and P = 0.727). CONCLUSION: In conclusion, this study emphasizes the significant association between BRAF polymorphism and thyroid cancer risk, while RET polymorphism showed a less pronounced impact. Further validation using larger and specific datasets is essential to establish conclusive results.

Mathematical study of polycystic ovarian syndrome disease including medication treatment mechanism for infertility in women.

Among women of reproductive age, PCOS (polycystic ovarian syndrome) is one of the most prevalent endocrine illnesses. In addition to decreasing female fertility, this condition raises the risk of cardiovascular disease, diabetes, dyslipidemia, obesity, psychiatric disorders and other illnesses. In this paper, we constructed a fractional order model for polycystic ovarian syndrome by using a novel approach with the memory effect of a fractional operator. The study population was divided into four groups for this reason: Women who are at risk for infertility, PCOS sufferers, infertile women receiving therapy (gonadotropin and clomiphene citrate), and improved infertile women. We derived the basic reproductive number, and by utilizing the Jacobian matrix and the Routh-Hurwitz stability criterion, it can be shown that the free and endemic equilibrium points are both locally stable. Using a two-step Lagrange polynomial, solutions were generated in the generalized form of the power law kernel in order to explore the influence of the fractional operator with numerical simulations, which shows the impact of the sickness on women due to the effect of different parameters involved.

Analysis and dynamical structure of glucose insulin glucagon system with Mittage-Leffler kernel for type I diabetes mellitus.

In this paper, we propose a fractional-order mathematical model to explain the role of glucagon in maintaining the glucose level in the human body by using a generalised form of a fractal fractional operator. The existence, boundedness, and positivity of the results are constructed by fixed point theory and the Lipschitz condition for the biological feasibility of the system. Also, global stability analysis with Lyapunov's first derivative functions is treated. Numerical simulations for fractional-order systems are derived with the help of Lagrange interpolation under the Mittage-Leffler kernel. Results are derived for normal and type 1 diabetes at different initial conditions, which support the theoretical observations. These results play an important role in the glucose-insulin-glucagon system in the sense of a closed-loop design, which is helpful for the development of artificial pancreas to control diabetes in society.

Appraisal of contamination, source identification and health risk assessment of selected metals in the agricultural soil of Chakwal, Pakistan.

Contamination of metals in agricultural soil is a serious global threat but there are limited reports related to their risks in major agronomic areas. The current study is aimed to assess the distribution of selected macroelements and essential/toxic trace metals (Ca, Mg, Na, K, Sr, Li, Ag, Fe, Zn, Co, Cu, Mn, Cd, Cr, Pb and Ni) in the agricultural soil of Chakwal, Pakistan, in order to appraise their contamination status, source identification and probable human health risks. Quantification of the metals was performed by AAS employing aqua regia digestion method. Among the selected metals, dominant mean concentrations were observed for Ca (48,285 mg/kg) and Fe (30,120 mg/kg), followed by Mg (9171 mg/kg), K (973.3 mg/kg), Mn (399.0 mg/kg) and Na (368.9 mg/kg). The correlation study indicated strong mutual relationships among the metals as well as physicochemical properties. Multivariate analysis (PCA/CA) of the metal levels revealed their diverse anthropogenic sources in the soil. Various pollution indices indicated extremely high contamination/enrichment of Cd, followed by moderate enrichment/contamination of Ag in the soil. The HQ values for most of the metals manifested insignificant non-cancer risks. The average CR value of Cr was exceeding the safe limit (1.0E-06) for both ingestion and inhalation exposure, indicating a considerable lifelong cancer risk for the population. The results of this study will provide a better understanding related to the contamination of agricultural soil and its effects on human health and to promote effective actions to reduce the soil pollution.

Assessment of water quality, trace metal pollution, source apportionment and health risks in the groundwater of Chakwal, Pakistan.

Groundwater quality evaluation is the main concern in the regions like Chakwal where it is major source of water for drinking and irrigation due to low storage capacity of the surface water and lack of proper irrigation system. The aim of the present study was to evaluate various physicochemical parameters (pH, EC, TDS, DO, TA, TH and chlorides) and selected essential/toxic trace metal concentrations (Na, K, Ca, Mg, Sr, Li, Ag, Zn, Fe, Cu, Co, Mn, Cr, Cd, and Pb) in order to explore their distribution, correlation, spatial variations and health risk assessment. Average concentration of some trace metals (Co, Cd and Pb) and physicochemical parameters (EC, TDS, and alkalinity) were found to exceed the national/international standards. Multivariate methods of analysis showed strong associations among Fe-Li-K, Sr-Mg-Ca, Cd-Mn, Cu-Zn, Ag-Co, and Cr-Pb-Na which were significantly contributed by anthropogenic activities. Irrigation water quality index exhibited intermediate suitability of the groundwater for irrigation purpose. Health risk evaluation of the trace metals revealed significant non-carcinogenic risks for Cd, Co and Pb (HQing > 1) especially for children. Similarly, significant carcinogenic risk was found to be associated with Pb and Cr which exceeded the safe limit, suggesting the lifetime carcinogenic risk associated with these metals in the groundwater. The present health risk problems should be considered on top priority and immediate actions should be taken to safeguard the water quality in the study area.

Lipolysis and antioxidant properties of cow and buffalo cheddar cheese in accelerated ripening.

BACKGROUND: Buffalo milk is the second largest source of milk on the globe, it is highly suitable for the preparation of mozzarella cheese, however, it is not suitable for the preparation of cheddar cheese due to high buffering capacity, low acid development, excessive syneresis, lower lipolysis that lead to lower sensory score. Accelerated ripening can enhance lipolysis and improve sensory characteristics of cheddar cheese. Lipolysis and antioxidant capacity of buffalo cheddar cheese in conventional ripening is not previously studied. Optimization of ripening conditions can lead to better utilization of buffalo milk in cheese industry. METHODS: Effect of accelerated ripening on lipolysis and antioxidant properties of cow and buffalo cheddar cheese were investigated. Cheddar cheese prepared from standardized (3.5% fat) cow and buffalo milk was subjected to conventional and accelerated ripening (4 °C and 12 °C) for a period of 120 days. Fatty acid profile, organic acids, free fatty acids, cholesterol, antioxidant activity and sensory characteristics were studied at 0, 40, 80 and 120 days of ripening. RESULTS: Fatty acid profile of cow and buffalo cheddar in conventional (120 days old) and accelerated ripening were different from each other (p < 0.05). Free fatty acids in 120 days old buffalo and control cheddar, in accelerated ripening were 0.55% and 0.62%. After accelerated ripening, cholesterol in buffalo and control cheddars were 16 and 72 mg/100 g. After accelerated ripening, concentrations of formic, pyruvic, lactic, acetic and citric acids in buffalo cheddar cheese were, 922, 136, 19,200, 468 and 2845 ppm. At the end of accelerated ripening (120 days), concentrations of formic, pyruvic, lactic, acetic and citric acids in cow cheddar cheese were 578, 95, 9600, 347 and 1015 ppm. Total antioxidant capacity of control cow and buffalo cheddar in accelerated ripening was 77.26 and 88.30%. Colour, flavour and texture score of rapid ripened 80 and 120 days old buffalo cheddar was not different from cow cheddar. CONCLUSIONS: Results of this investigations showed that flavour profile buffalo cheddar subjected to accelerate ripening was similar to cow cheddar cheese. Accelerated ripening can be used for better utilization of buffalo milk in cheddar cheese industry.

Impact of immediate and delayed chilling of raw milk on chemical changes in lipid fraction of pasteurized milk.

BACKGROUND: In many developing countries, milk chilling facilities are not available on the farm where milk is produced, rather these are located at the distance of 10-12 km. After milking, it takes about 2-3 h to reach milk to the chilling facilities. The milk is then chilled and transported to the milk processing plants for thermal processing and value addition. In developing countries, shelf life of pasteurized milk is only 3 days, as compared to 7-10 days in developed countries. The factors which are responsible for the shorter shelf life of pasteurized milk should be discovered for the improvement of dairy sectors of these countries. The magnitude of chemical changes which takes place in un-chilled milk and their effect on fatty acids profile, antioxidant status and lipid oxidation is not previously studied. METHODS: Raw milk samples of the same farm were either rapidly chilled to 4 °C immediately or held at room temperature (35 ± 2 °C) for 2 h followed by rapid chilling to 4 °C. Immediately and delayed chilled raw milk samples were stored at 4 °C for 72 h. Both milk samples were pasteurized at 65 °C, filled in 250 ml transparent PET bottles and stored at 4 °C for 6 days. Fatty acid profile, selenium, zinc, total antioxidant capacity, total flavonoid content and 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity, free fatty acids, peroxide value and anisidine value were determined at different stages of the experiment. This experiment was repeated with milk of same farm for at least five times. RESULTS: Storing raw milk at ambient temperature (35 ± 2 °C) significantly influenced the pH and lactose content of milk. The loss of short-chain fatty acids in delayed chilled milk was 1.19%, 3.27% and 1.60%, as compared to immediately chilled raw milk. In delayed chilled milk, loss of C18:1 and C18:2 after 3 days of storage period was 6.67% and 01.22. In delayed chilled milk after 6 days of storage, loss of C18:1 and C18:2 was 7.7% and 1.39%, respectively. In immediately chilled milk loss of C18:1 and C18:2 after 3 days of storage was 3.48% and 0.64%. In immediately chilled milk loss of C18:1 and C18:2 after 6 days of storage was 4.57% and 0.9%. Almost 41% vitamin E was lost when raw milk was stored at ambient temperature for 2 hrs. About 21% and 7% vitamin E was lost in delayed and immediately chilled milk, when samples were analyzed immediately after pasteurization. Loss of selenium and zinc contents after 2 h of ambient storage of raw milk were 0.43 and 224 µg/100 g. After 2 h of storage of milk at ambient temperature, free fatty acids increased by 0.03% (p < 0.05). After 6 days of storage, rise of free fatty acids in immediately and delayed chilled milk was 0.06% and 0.14%, respecitively. Rise of 0.13(MeqO2/kg) was recorded, when un-chilled raw milk was stored at ambient temperature for 2 h. After 3 and 6 days of storage, peroxide value of pasteurized milk (delayed chilled) was 0.88 and 1.56 (MeqO2/kg). After 3 and 6 days of storage, peroxide value of pasteurized (immediately chilled) was 0.39 and 0.42(MeqO2/kg). After 2 hrs of ambient storage, 18.41% flavonoids were lost. After 2 hrs of ambient storage of raw milk, loss of total antioxidant capacity and DPPH free radical scavenging activity was 29.31% and 44.53%. After 6 days of pasteurization, loss of total antioxidant capacity and DPPH free radical scavenging activity in delayed chilled raw milk was 72.1% and 89.57%. CONCLUSIONS: The findings of this investigation showed that delayed chilling of raw milk leads to several undesirable chemical changes in lipid fraction of milk.

Impact of vitamin E and selenium on antioxidant capacity and lipid oxidation of cheddar cheese in accelerated ripening.

BACKGROUND: Ripening of cheddar cheese is a time taking process, duration of the ripening may be as long as one year. Long ripening time is a big hindrance in the popularity of cheese in developing countries. Further, energy resources in these countries are either insufficient or very expensive. Therefore, those methods of cheese ripening should be discovered which can significantly reduce the ripening time without compromising the quality characteristics of cheddar cheese. In accelerated ripening, cheese is usually ripened at higher temperature than traditional ripening temperatures. Ripening of cheddar cheese at high temperature with the addition of vitamin E and selenium is not previously studied. This investigation aimed to study the antioxidant activity of selenium and vitamin E in accelerated ripening using cheddar cheese as an oxidation substrate. METHODS: The ripening of cheddar cheese was performed at 18 °C and to prevent lipid oxidation, vitamin E and selenium were used alone and in combination. The treatments were as: cheddar cheese without any addition of vitamin E and selenium (T1), cheddar cheese added with 100 mg/kg vitamin E (T2), 200 mg/kg vitamin E (T3), 800 µg/kg selenium (T4), 1200 µg/kg selenium (T5), vitamin E 100 mg/kg + 800 µg/kg selenium (T6) and vitamin E 200 mg/kg + 1200 µg/kg selenium (T7). Traditional cheddar cheese ripne ripened at 4-6 °C for 9 months was used as positive control. Cheese samples were ripened at 18 °C for a period of 12 weeks and analyzed for chemical and oxidative stability characteristics at 0, 6 and 12 weeks of storage. All these treatments were compared with a cheddar cheese without vitamin E, selenium and ripened at 4 °C or 12 weeks. Vacuum packaged cheddar cheese was ripened 18 °C for a period of 12 weeks and analyzed for chemical and oxidative stability characteristics at 0, 4 and 8 weeks of storage period. RESULTS: Addition of Vitamin E and selenium did not have any effect on moisture, fat and protein content of cheddar cheese. After 6 weeks of ripening, total antioxidant capacity of T1, T2, T3, T4, T5, T6, T7 and standard cheese were 29.61%, 44.7%, 53.6%, 42.5%, 41.4%, 64.1%, 85.1% and 25.4%. After 6 weeks of ripening, reducing power of T1, T2, T3, T4, T5, T6, T7 and SC cheese were 14.7%, 18.1%, 26.3%, 19.2%, 25.3%, 33.4%, 40.3% and 11.6%. After 6 weeks of ripening, 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity of T6 and T7 were 54.2% and 66.9%. While, DPPH free radical scavenging activity of T1 and standard cheese after 6 weeks of ripening were, 19.1 and 18.5%, respectively. Free fatty acids of vitamin E and selenium supplemented, non-supplemented and standard cheese were not significantly influenced from each other in 0, 6 and 12 weeks old cheddar cheese. Peroxide values of T1, T2, T3, T4, T5, T6, T7 and standard cheese after 6 weeks of accelerated ripening were 1.19, 1.05, 0.88, 1.25, 0.29, 0.25, 0.24 and 0.28 (MeqO2/kg). After 6 weeks of ripening, anisidine value of T6 and T7 were 6.55 and 6.14. Conjugated dienes of T1, T2, T3, T4, T5, T6, T7 and standard cheese, after 6 weeks of accelerated ripening were 0.61, 0.55, 0.42, 0.77, 0.65, 0.17, 0.15 and 0.19. After 6 weeks of accelerated ripening, concentrations unsaturated fatty acids in T1, T2, T3, T4, T5, T6, T7 and standard cheese decreased by18.19%, 17.45%, 16.82%, 16.19%, 12.71%, 8.48%, 6.92% and 14.71%. After 12 weeks of accelerated ripening, concentration of unsaturated fatty acids in T1, T2, T3, T4, T5, T6 and T7 and standard cheese decreased by 26.2%, 21.2%, 18.7%, 14.2%, 10.4%, 4.84%, 1.03% and 6.78%. Cheddar cheese samples added with vitamin E, selenium and their combinations produced more organic acids during the ripening period of 12 weeks. After 6 and 12 weeks of ripening, flavor score of T6 and T7 was better than standard ripened cheddar cheese. CONCLUSIONS: After 6 weeks of accelerated ripening, sensory characteristics of T6 and T7 were similar to cheddar cheese that was ripened at 4 °C for 9 months. Ripening time of cheddar cheese may be reduced to 6 weeks by elevated temperature (18 °C) using vitamin E and selenium as antioxidants at T6 and T7 levels.