T4 Ratio Research Articles

Thermoregulatory dysfunction in post‐weaning congenic corpulent rats

To assess the capacity for cold induced thermoregulation in congenic corpulent rats, groups of normally fed post‐weaning lean and obese LA/Ntul//‐cp rats 6‐9 weeks of age were subjected to a 24°C vs. 4°C environment for < 14 hours. Measures of resting VO2 (RMR) and the thermoregulatory responses to cold exposure, the thermic response to noradrenaline, thyroidal parameters, and measures of core and peripheral body temperatures following cold exposure were obtained. Body weights of obese were greater than in lean rats (p=<0.01), and 14 hours of 4°C exposure demonstrated phenotype effects on both core and rectal temperatures (lean > obese, rectal p=0.0012, core p= 0.0038). The RMR at thermal neutrality and the thermic response to 45 minutes of acute 4°C cold exposure was greater in lean than obese phenotype at all time points measured. The thermic responses to 100 vs 200 µg NE s.c. were greater in lean than in obese rats. Cold exposure induced a significant increase in circulating T3 and the T3:T4 ratios but T4 concentrations were unchanged by cold exposure challenge. Phenotype effects on outer ring T4‐5’ deiodinase activity/mg protein were present in Kidney and Liver (Lean > Obese) while Interscapular brown adipose tissue (IBAT) demonstrated both phenotype and cold induced effects (Obese > Lean). In contrast, T4‐5’deiodinase activity in gastrocnemius muscle tissue was similar in both phenotypes and lacked cold induced effects (p= n.s.). The results of this study indicate that an impaired capacity for thermoregulation occurs early in the lifespan of the corpulent rat, despite a robust increase in total IBAT 5’deiodinase activity and in circulating T3 concentrations following cold exposure in both lean and obese phenotypes. While the physiologic basis for the elevated T3 concentrations following cold exposure remains unclear and are likely secondary to the combined effects of optimizing peripheral T4 to T3 conversion rates in both phenotypes, and possible changes in kinetics of T3 receptor binding and clearance in IBAT and other tissues and which may contribute to a greater caloric efficiency and propensity for weight gain in the obese phenotype.

Impact of Plant Geometry and Zinc on Growth and Yield Attributes of Sweet Corn (Zea mays L.)

During Zaid 2021, a field experiment was undertaken at the Crop Research Farm, Department of Agronomy, SHUATS, Prayagraj (U.P). The experiment was set up using a Randomized Block Design, with nine treatments reproduced three times over the course of a year. The treatments which are T1: 40cm x 20 cm + 15 kg/ha ZnSO4, T2: 40cm x 20 cm + 20 kg/ha ZnSO4, T3: 40cm x 20 cm + 25 kg/ha ZnSO4, T4: 50cm x 20 cm + 15 kg/ha ZnSO4, T5: 50cm x 20 cm + 20 kg/ha ZnSO4, T6: 50cm x 20 cm + 25 kg/ha ZnSO4, T7: 60cm x 20 cm + 15 kg/ha ZnSO4, T8: 60cm x 20 cm + 20 kg/ha ZnSO4, T9: 60cm x 20 cm + 25 kg/ha ZnSO4 used. The results showed that application of 60cm x 20 cm + 25 kg/ha ZnSO4 recorded significantly highest plant height (166.02 cm), Number of leaves/plant (12.25), Dry weight/plant (141.58 g/plant), number of cobs/plant (1.76), length of the cob/plant (16.90 cm), Cob girth (15.46 cm) whereas maximum crop growth rate (48.65 g/m2/day) was recorded with treatment 40cm x 20 cm + 25 kg/ha ZnSO4 whereas, cob yield (6.45 t/ha) and Green fodder yield (20.55 t/ha) recorded maximum in 40cm x 20 cm + 25 kg/ha ZnSO4..The treatment with 40 x 20 cm spacing and application of 25 kg of zinc is advised for recommendation, as it is recorded maximum cob yield, green fodder yield, and benefit cost ratio in treatment T3.

Extended Lymphadenectomy for Proximal Transverse Colon Cancer: Is There a Place for Standardization?

Background and Objectives: Complete mesocolon excision and high vascular ligation have become a standard procedure in the treatment of colon cancer. The transverse colon has certain embryological and anatomical particularities which require special attention in case of oncological surgeries. Proximal transverse colon cancer (TCC) can metastasize to the lymph nodes in the gastrocolic ligament. The aim of this study is to assess the tumor involvement of these lymph nodes and to determine the applicability of gastrocolic ligament lymph nodes dissection as the standard approach for proximal transverse colon cancer. Materials and Methods: this study analyzes the cases of patients admitted to the Surgery Department, diagnosed with proximal transverse colon cancer, with tumor invasion ≥ T2 and for which complete mesocolon excision with high vascular ligation and lymphadenectomy of the gastrocolic ligament (No. 204, 206, 214v) were performed. Results: A total of 43 cases operated during 2015–2020 were included in the study. The median total number of retrieved central lymph nodes was 23 (range, 12–38), that had tumor involvement in 22 cases (51.2%). Gastrocolic ligament tumor involvement was found in 5 cases (11.6%). The median operation time was 180 min, while the median blood loss was 115 mL (range 0–210). The median time of hospitalization was 6 days (range, 5–11). Grade IIIA in the Clavien-Dindo classification was noticed in 3 patients, with no mortality. Upon Kaplan–Meier analysis, tumors > T3 (p < 0.016) and lymph node ratio < 0.05 (p < 0.025) were statistically significant. Conclusions: lymph node dissection of the gastrocolic ligament in patients with advanced proximal transverse colon cancer may improve the oncological outcome in T3/T4 tumors, and therefore standardization could be feasible

Effects of estuarine oyster, Crassostrea cuttackensis as the extractive species at varied densities on productivity and culture environment in brackishwater integrated multi-trophic aquaculture (BIMTA) system

Integrated multi-trophic aquaculture (IMTA) involves incorporation of species from different trophic or nutritional levels in the same system to get better production based on mutual gain to the co-cultured species and improved ecosystem health. However, in brackishwater, very few trials on IMTA have been conducted so far with scarce information on the optimum density of extractive species like oyster and seaweed. Edible estuarine oyster, Crassostrea cuttackensis is abundantly available in the Sundarban. Being a filter-feeder, it can be used as an extractive species for organic matter removal in IMTA. Therefore, an experimental trial was conducted to assess the effect of different stocking densities of C. cuttackensis on performances of milkfish (Chanos chanos) and Pacific white-leg shrimp (Penaeus vannamei), and environmental remediation in an IMTA system. There were three densities of oyster, 0.6 (T1), 1.2 (T2), and 1.8 (T3) kg m−3 distributed to 1000 L FRP circular tanks containing milkfish (4.51 ± 0.05 g) and white-leg shrimp (4.50 ± 0.03 g) at 25 and 50 no. m−3, respectively. Control tanks contained the same number of milkfish and shrimp with no oyster. All the three treatments and control had triplicate tanks. During the 60-day trial period, fish and shrimp were fed with a common diet containing 30% crude protein at 5% of biomass. Results showed that the highest growth of milkfish (24.66 ± 0.31 g) and shrimp (15.20 ± 0.17 g) was obtained in T3 (P < 0.05) compared to that of the control [13.97 ± 0.08 g (milkfish), 11.83 ± 0.13 g (shrimp)]. Apparent feed conversion ratio (AFCR) was the lowest in T3 (0.92 ± 0.01) (P < 0.05). Although, survival of milkfish did not vary, shrimp survival was the highest in T3. The inorganic nutrients (nitrogenous and phosphorus compounds) and particulate organic matter (POM) of water improved in all the IMTA treatments compared to the control. The number of total heterotrophic bacteria and Vibrio counts in tank water was significantly low in T3 (P < 0.05). The benefit-cost ratio in T3 was found to be 1.6 times higher than that of the control. This trial suggested that oyster, C. cuttackensis can act as an effective extractive species in IMTA system when stocked at a density of 1.8 kg m−3. Therefore, treatment T3 IMTA model proved to be more productive and had a successful bio-remediation effect on the environment.

Associations between Oxidative/Nitrosative Stress and Thyroid Hormones in Pregnant Women-Tainan Birth Cohort Study (TBCS).

Oxidative and nitrosative stress have been linked to thyroid function in both animal and human studies. In the present study, the associations between oxidative and nitrosative stress and thyroid hormones were investigated. Measurements were obtained from 97 Taiwanese pregnant women at the first, second, and third trimesters. Levels of five oxidative and nitrosative stress biomarkers (8-hydroxy-2′-deoxyguanosine [8-OHdG], 8-nitroguanine [8-NO2Gua], 4-hydroxy-2-nonenal-mercapturic acid [HNE-MA], 8-isoprostaglandin F2α [8-isoPGF2α], and malondialdehyde [MDA]) were measured using urine samples, and levels of five thyroid hormones (triiodothyronine [T3], thyroxine [T4], free T4, thyroid-stimulating hormone [TSH], and T4-binding globulin [TBG]) were measured in blood samples. Multiple linear regressions and linear mixed-model regressions were conducted to determine the associations between oxidative or nitrosative stress biomarkers and thyroid hormones in pregnant women. We found that TSH was negatively and significantly associated with 8-NO2Gua (−14%, 95% CI [−26.9% to −1.1%]) and HNE-MA (−23%, 95% CI [−35.9% to −10.0%]) levels. However, T4 (3%, 95% CI [0.2%–5.8%]) and free T4 (4.3%, 95% CI [0.8%–7.8%]) levels were positively and significantly associated with 8-NO2Gua. The T4 to TBG and free T4 to TBG ratios were positively and significantly associated with 8-NO2Gua level (T4/TBG: 3.6%, 95% CI [0.5%–6.7%]; free T4/TBG: 5.6%, 95% CI [0.2%–11.1%]). However, the TSH to T4 ratio was negatively and significantly associated with 8-NO2Gua level (−17.3%, 95% CI [−30.4% to −4.3%]). The T3 to TSH ratio was positively and significantly associated with HNE-MA level (25.2%, 95% CI [11.2%–39.2%]). However, the TSH to T4 and TSH to free T4 ratios were negatively and significantly associated with HNE-MA level (TSH/T4: −21.2%, 95% CI [−34.5% to −7.8%] and TSH/free T4: −24.0%, 95% CI [−38.3% to −9.6%]). Our findings suggest that an imbalance of oxidative and nitrosative stress may alter thyroid hormone homeostasis during pregnancy. Disruption of the maternal thyroid homeostasis during pregnancy would affect embryonic and fetal development.

Association of Reduced Free T3 to Free T4 Ratio with Lower Serum Creatinine in Japanese Hemodialysis Patients.

Purpose: Low T3 syndrome is defined by a fall in free triiodothyronine (FT3) in spite of normal serum thyroid-stimulating hormone (TSH) and often normal free thyroxin (FT4). A low FT3/FT4 ratio, a relevant marker for low T3 syndrome, is known as a risk of mortality in hemodialysis (HD) patients, as well as low muscle mass in the general population. Because of the local activation of T4 to FT3 in muscle tissue, we examined the association of FT3/FT4 ratio with serum creatinine, a marker of muscle mass and strength in HD patients to investigate the significance of muscle tissue in the development of low T3 syndrome in HD patients. Methods: This was a cross-sectional study derived from our prospective cohort study, named DREAM, of Japanese HD patients. After the exclusion of patients with treated and untreated thyroid dysfunction, 332 patients were analyzed in the study. Results: The serum FT4 and TSH of HD patients (n = 332) were 0.9 ± 0.1 ng/dL. and 2.0 ± 0.9 μIU/mL, which were within the respective normal range, while serum FT3 was 2.2 ± 0.3 pg/mL. As many as 101 out of 332 (30.4%) HD patients exhibited a serum FT3 less than the normal lower limit of 2.2 pg/mL. The serum FT3/FT4 ratio correlated significantly positively with serum creatinine, and inversely with serum log CRP and total cholesterol, while it exhibited a tendency towards positive correlation with serum albumin. Multiple regression analysis, which included serum creatinine, albumin, and log CRP, simultaneously, in addition to sex, age, diabetic kidney disease or not, log HD duration, body mass index, systolic blood pressure, and Kt/V, as independent variables, revealed an independent and significant positive association of serum creatinine, but not serum albumin or CRP, with the serum FT3/FT4 ratio. Conclusions: The present study demonstrated an independent and positive correlation of serum creatinine with the serum FT3/FT4 ratio in HD patients. The lack of association of the serum FT3/FT4 ratio with serum albumin and CRP suggested the presence of a creatinine-specific mechanism to associate with serum FT3/FT4 ratio. Because of the local activation of T4 to T3 at muscle tissue, a lower muscle mass may be causatively associated with low T3 syndrome.

Assessment of Stirred Probiotic Yogurt fortified with Husk Tomato (Physalis peruviana, L) Juice as a Healthy Dairy Product

Consumers are increasingly aware of the consumption of natural health products. Husk Tomato fruit is a remarkable fruit in a modern survey. Therefore, this study aims to produce novel stirred probiotic yogurt (SPY) fortified with Husk Tomato Juice (HTJ). Chemical, microbiological, toxins, color, and viscosity characteristics for the new product were evaluated. Vitamins A, B1, B2, C, amino acid profile, and the effect of HTJ or SPY on the growth of some pathogens were assessed. Vitamin A and β-carotene for fresh stirred probiotic yogurt were also analyzed. On the other side, the control sample (with no fortification) and four treatments of SPY were produced with different ratios of Husk Tomato Juice T1, T2, T3, and T4 with (20, 30, 40, and 50% V/V) respectively. Apparent viscosity, color parameters, and pH values of fermented beverage samples were estimated. Data revealed that the juice had a considerable vitamin C ratio, representing about 32-38% of the recommended daily use. On the same line, Lysine, Leucine, Valine, Threonine, Tryptophan, and Isoleucine were the main essential amino acids in the juice. Also, the HTJ possessed diverse degrees of inhibition opposite to grow of some pathogenic bacteria and fungi. The counts of starter cultures of yogurt and Lb. casei as the probiotic strain increased during the storage period until 10 days, especially in T1, T2, and T3. The viable counts of pathogenic strains in the contaminated treatments decreased during storage periods compared with control. Furthermore, treatment samples had significantly lower L values and higher a &amp; b values due to the orange color of the high ratio of β-carotene in HTJ compared to control samples. A healthy probiotic fruity beverage had been successfully produced. It has appropriate amounts of important vitamins.

Sugammadex Reduces PACU Recovery Time after Abdominal Surgery Compared with Neostigmine

This study blindly evaluated sugammadex compared with neostigmine on length of stay in the postanesthesia care unit (PACU). Fifty patients undergoing elective laparoscopic cholecystectomy or abdominal wall hernia repair consented to receive either sugammadex (2 mg/kg) or neostigmine (0.07 mg/kg) for the reversal of rocuronium neuromuscular blockade. Reversal agents were administered during surgical closing, and the train of four was measured until a twitch ratio of T4:T1 ≥ 0.9 was obtained to signify a robust reversal. Postreversal outcomes also were measured during PACU stay. Aldrete scores, pain visual analog scale score, and nausea were measured during the PACU stay. Patients receiving sugammadex experienced a shorter PACU stay at the time of discharge than patients receiving neostigmine, by an average of 12 minutes (P < 0.05). Sugammadex patients had a significantly shorter PACU stay.

Correlation between inflammatory parameters and pituitary-thyroid axis in patients with COVID-19.

PurposeInflammation plays a critical role in the progression of COVID-19. Nonthyroidal illness syndrome (NTIS) has been increasingly recognized in affected patients. We aim to evaluate the correlation of thyroid hormones with markers of inflammation and association with disease outcome in hospitalized patients with COVID-19, and in two profiles of NTIS (low T3-normal/low FT4 vs. low T3-high FT4).Methodsconsecutive patients admitted to a nonintensive care unit for COVID-19 were recruited. Infection was mild in 22%, moderate in 27.1% and severe in 50.8%; 7.41% died. T4, T3, FT4, FT3, and their ratios (T3/T4, FT3/FT4) were correlated with albumin, ferritin, fibrinogen, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), lactate dehydrogenase (LDH), and D-dimer.ResultsFifty five patients (50.9% men, median age 56 years) were included. Albumin correlated positively with T3 and hormones ratios, but negatively with FT4. T3, FT3, T3/T4, and FT3/FT4 correlated inversely with ferritin, fibrinogen, ESR, CRP, LDH, and D-dimer. FT4 showed direct correlation with fibrinogen and ESR. T3/T4 was lower in severe compared to mild/moderate disease [7.5 (4.5–15.5) vs. 9.2 (5.8–18.1); p = 0.04], and lower in patients who died than in those discharged [5 (4.53–5.6) vs. 8.1 (4.7–18.1); p = 0.03]. A low T3/high FT4 profile was associated with lower albumin, higher ferritin, and severity.ConclusionIn this cohort, thyroid hormones correlated with inflammation and outcome. T3 and T3/T4 correlated inversely with inflammatory markers; a low T3/T4 ratio was associated with severity and poor prognosis. Patients with low T3 but high FT4 had higher ferritin, lower albumin, and more severe disease at presentation.

Age-related changes in thyroid hormones, some serum oxidative biomarkers and trace elements and their relationships in healthy Saanen goat kids during the first three month of age.

Early-life diseases in dairy animals are main causes of economic loss in livestock production. Oxidative stress (OS) and thyroid hormones are important inter-related components in the normal physiology of this critical period of life. However, limited information regarding their physiology in goat kids is available. This study was conducted to investigate the age-related changes of thyroid hormones, some serum oxidative biomarkers and trace elements in healthy Saanen goat kids. Nineteen newborn healthy Saanen goat kids (14 females and five males) were studied longitudinally from birth until three months of age. Blood sampling was performed 24-48h after birth and was repeated on 10±2, 28±2, 56±2 and 84±2days of age. The serum levels of thyroid hormones, malondialdehyde (MDA), reduced glutathione (GSH), total antioxidant capacity (TAC), selenium (Se), manganese (Mn) and molybdenum (Mo) were measured. Age-related changes were observed for all measured variables except for MDA (p<0.05). A decreasing trend was detected throughout the study in thyroid hormones, T3: T4 ratio and Mn (p<0.01). Some factors decreased from birth to day 10 (Se) or day 28 (TAC and GSH) and followed by an increasing trend that extended to day 84 (p<0.01). There were significant correlations between thyroid hormones and TAC, as well as Mn levels (p<0.05). These results imply that specific age-related reference values are essential for proper interpretation of the serum level of thyroid hormones and Mn in Saanen goat kids during the first three months of life. In addition, given the high level of thyroid hormones particularly during the first days of life, and their relationship with oxidative biomarkers and trace elements, improving the antioxidant system in this critical period is essential.

Clinical analysis of ocular adnexal mucosa-associated lymphoid tissue lymphoma with IgG4-related ophthalmic disease

ABSTRACT Purpose To analyse the incidence and characteristics of ocular adnexal mucosa-associated lymphoid tissue lymphoma (OAML) with immunoglobulin G4 (IgG4)-related ophthalmic disease (IgG4-ROD), and to compare with IgG4-negative OAML. Methods We enrolled 130 patients with pathology-confirmed OAML at a single tertiary medical centre. Patients were divided into IgG4-positive and IgG4-negative groups based on the pathologic criteria for IgG4-ROD. The data were reviewed and compared between the groups. Results IgG4-positive OAML was identified in 5.4% (7/130) of OAML and 13.5% (7/52) of non-conjunctival OAML. IgG4-positive group had a higher incidence of involvement of the lacrimal gland (7/7 vs. 18/123, p = .001), extraocular muscles (3/7 vs. 10/123, p = .022) and infraorbital nerve (2/7 vs. 0/123, p < .001), and had a lower incidence of involvement of the conjunctiva (0/7 vs. 84/123; p < .001) than IgG4-negative group. IgG4-positive group had higher T and N categories of the American Joint Committee on Cancer classification (T1:T2:T3:T4 ratio of 0:6:0:1 vs. 78:32:8:5, p < .001; and ≥N1 ratio of 2/7 vs. 7/123, p = .021). There were no differences in the response rate to initial treatment (5/6 vs. 39/41, p = .343) or the relapse rate (1/6 vs. 5/41, p = 1.000) between the groups. Conclusion IgG4-positive OAML showed clinical features similar to IgG4-ROD, such as predominant disease involvement of the lacrimal gland, extraocular muscles, infraorbital nerve and lymph nodes, but not the conjunctiva. However, treatment outcomes were favourable with or without background IgG4-ROD. Physicians should be aware that IgG4-ROD might undergo a malignant transformation and that thorough treatment and surveillance of IgG4-ROD are important.

Gestational acrylamide exposure and biomarkers of fetal growth: Probing the mechanism underlying the association between acrylamide and reduced fetal growth

IntroductionFour epidemiological studies have shown a negative association between prenatal acrylamide exposure and birth size. In order to shed light on the possible underlying mechanism(s), we analysed associations between acrylamide biomarkers and biomarkers related to fetal growth. MethodsIn newborns of the ENVIRONAGE birth cohort (n ranges from 215 to 434), we investigated the association between prenatal acrylamide exposure (acrylamide and glycidamide hemoglobin adduct levels in cord blood) and thyroid hormones (TSH, T3, T4 and the ratio of T4 to T3 in cord plasma), insulin-related factors (cord plasma insulin and IGF1, and placental IGF2), neurotrophins (cord plasma BDNF, and placental NGF, NT3 and NT4), and cord plasma homocysteine and progesterone, using multiple linear regression analysis. In addition, we investigated whether the biomarkers mediated the associations between prenatal acrylamide exposure and birth outcomes. ResultsWe observed lower cord plasma TSH (−10.2% [95% CI: −15.0, −4.3]) and higher placental NGF levels (10.0% [95% CI 3.7, 17.4]) for a twofold increase of acrylamide adducts, a decrease in the ratio of cord plasma free T4 and free T3 with higher acrylamide and glycidamide adducts of −2.9% (95% CI: −5.7, −0.1) and −3.9% (95% CI: −6.2, −1.6) for a twofold increase in acrylamide and glycidamide adduct levels, respectively, and higher cord plasma free T3 with increases in both acrylamide and glycidamide adducts of 2.8% (95% CI: 0.2, 5.6) and 3.6% (95% CI: 0.8, 6.6) for a twofold increase in acrylamide and glycidamide adduct levels, respectively. Additionally, a twofold increase in glycidamide adducts was associated with lower cord plasma insulin levels, particularly among newborns of non-smoking mothers (−11.2% [95% CI: −19.5, −0.1]).Cord plasma insulin seemed to mediate the association between glycidamide adducts and birth weight. ConclusionsA decrease in cord plasma insulin levels may be (a marker of) a mechanism by which gestational acrylamide exposure is associated with decreased fetal growth. The possible health consequences of the associations between gestational acrylamide exposure and thyroid hormones and neurotrophins warrant future study.

A prolonged hiatus in postmenopausal HRT, does not nullify the therapy's positive impact on ageing related sarcopenia.

BackgroundPrevious work suggest a positive skeletal muscle effect of hormone replacement therapy (HRT) on skeletal muscle characteristics This study aimed to quantify any continued positive effect of HRT even after a sustained hiatus in treatment, controlling for two key muscle modulation hormones: Estradiol (E2) and Tri-iodo-thyronine (T3).Method and findingsIn 61 untrained women (18-78yrs) stratified as pre-menopausal, post-menopausal without (No_HRT) and post-menopausal with (Used_HRT) HRT history, body composition, physical activity, serum E2 and T3 were assessed by dual energy x-ray absorptiometry, Baecke questionnaire and ELISA. Gastrocnemius medialis (GM) and tibialis anterior (TA) electromyographic profiles (mean power frequency (mPowerF)), isometric plantar-flexion (PF) and dorsi-flexion (DF) maximum voluntary contraction (MVC), rate of torque development (RTD), isokinetic MVC and muscle volume, were assessed using surface electromyography, dynamometry and ultrasonography. Muscle quality was quantified as MVC per unit muscle size. E2 and E2:T3 ratio were significantly lower in postmenopausal participants, and were positively correlated with RTD even after controlling for adiposity and/or age. Pre-menopausal females had greater MVC in 8/8 PF and 2/5 DF (23.7–98.1%; P<0.001–0.049) strength measures compared to No_HRT, but only 6/8 PF (17.4–42.3%; P<0.001–0.046) strength measures compared to Used_HRT. Notably, Used_HRT had significant higher MVC in 7 PF MVC (30.0%-37.7%; P = 0.006–0.031) measures than No_HRT, while premenopausal and Used_HRT had similar uncorrected muscle size or quality. In addition, this cross-sectional data suggest an annual reduction in GM muscle volume corrected for intra-muscular fat by 1.3% in No_HRT and only 0.5% in Used_HRT.ConclusionEven years after cessation of the therapy, a history of HRT is positively associated with negating the expected post-menopausal drop in muscle quantity and quality. Whilst mPowerF did not differ between groups, our work highlights positive associations between RTD against E2 and E2:T3. Notwithstanding our study limitation of single time point for blood sampling, our work is the first to illustrate an HRT attenuation of ageing-related decline in RTD. We infer from these data that high E2, even in the absence of high T3, may help maintain muscle contractile speed and quality. Thus our work is the first to points to markedly larger physiological reserves in women with a past history of HRT.

Reverse T3 Level and T3 to Reverse T3 Ratio in Dried Blood Spot Samples at Birth May Facilitate Early Diagnosis of MCT8 Deficiency

Background: Monocarboxylate transporter 8 (MCT8) deficiency is an X- chromosome-linked neurodevelopmental disorder resulting from impaired thyroid hormone transporter across cell membrane. The diagnosis of MCT8 deficiency is typically delayed owing to the late appearance of signs and symptoms as well as inability of standard biomarkers of neonatal screening to make an early diagnosis. Here, we report for the first time the ability to identify MCT8 deficiency at birth using dried blood spot (DBS) samples. Methods: We measured T3, T4, and reverse T3 (rT3) levels in DBS samples obtained at birth in healthy neonates (n = 42) and neonates with genetically confirmed diagnosis of MCT8 deficiency (n = 6). T3, rT3 and T4 levels were measured in 8 mm diameter DBS samples using liquid chromatography-tandem mass spectrometry. Results: Mean ± SD level of T3 tended to be higher in the MCT8 group than that in healthy neonates (0.941 ± 0.183 ng/mL vs. 0.742 ± 0.195 ng/mL, p = 0.0525). More importantly rT3 level in the MCT8 group was significantly lower than that in healthy neonates (0.317 ± 0.065 ng/mL vs. 0.768 ± 0.196 ng/mL, p < 0.0001) and the T3/rT3 ratio in the MCT8 group was significantly higher (3.04 ± 0.67 vs. 1.01 ± 0.34, p < 0.0001) with no overlap of values. T4 was lower in the MCT8 group than in healthy babies (93.4 ± 22.4 ng/mL vs. 156.7 ± 35.9 ng/mL, p < 0.0005) and the T3/T4 ratio of the MCT8 deficient group was higher (0.0105 ± 0.0029 vs. 0.0051 ± 0.0010, p< 0.0001). Conclusion: rT3 and T3/rT3 ratio measured in the DBS obtained from neonates can serve as biomarkers for diagnosis of MCT8 deficiency at birth.

High-Dose Levothyroxine for Bipolar Disorder; the Potential Role of Thyroid Function and Genetic Tests. Report from Twenty Cases.

Rationale: Rapid Cycling Bipolar Disorder (RCBPD) is a malignant course of bipolar disorder (BPD). The condition is associated with several co-morbidities and is difficult to treat. Supra- physiologic doses of levothyroxine (average 482 µg/day) (High-Dose Levothyroxine, HDL) have proven effective for treatment resistant BPD. It is unclear exactly how HDL benefits patients with BPD. Objectives: In this paper, we present the retrospective analysis of clinical notes of 20 patients in remission from RCBPD for at least six months, who received HDL (150-1000 µg; median 472 µg/day). We examine the role of Thyroid function tests (TFTs) and genetic testing. We aim to demonstrate the utility of these tests for patient selection and response prediction for HDL. Findings: All patients recovered with minimal side effects with no treatment discontinuations. One patient required a dose reduction because of palpitations and sweating. Seventeen patients had concomitant Repetitive Transcranial Magnetic Stimulation (rTMS). Ten patients (50%) required one psychotropic in the acute phase, two patients (10%) required two and eight patients (40%) required only HDL. Following remission, 11 patients (55%) were on HDL only. The average pre-treatment ratio of free T4 (thyroxine, fT4): free T3 (triiodothyronine, fT3) was 4:1, with fT4 increasing post-treatment to 5:1 while fT3 remained largely normal. Nineteen patients had single nucleotide polymorphism (SNPs) of DIO1, DIO2 , or both. One subject requiring 400 µg had a SNP in the SLCO1C1 thyroid carrier. A high fT4:fT3 noted as early as day 10 during treatment supports a role for DIO polymorphisms. Conclusions: This preliminary report demonstrates the usefulness of a high fT4/fT3 ratio in the second week as a predictive test for patient selection and response prediction for HDL. Recently we have developed a treatment protocol combining HDL and rTMS.

Growth hormone replacement may influence the biological action of thyroid hormone on liver and bone tissue

ObjectiveGrowth hormone (GH) replacement alters the peripheral interconversion of thyroxine (T4) and triiodothyronine (T3). However, little is known about the clinical impact of these alterations. We aimed to compare changes observed in the serum T3:T4 ratio with known biological markers of thyroid hormone action derived from different peripheral tissues. DesignWe prospectively studied twenty GH deficient men before and after GH replacement in a tertiary referral endocrine center. Serum biochemical measurements included insulin like growth factor-1 (IGF-1), thyroid hormones (free & total T3, free & total T4 and reverse T3) and TSH. Changes in thyroid hormone concentration were compared to alterations in hepatic and bone biomarkers of thyroid hormone action. ResultsGH replacement provoked a decline in serum free T4 concentration (−1.09 ± 1.99 pmol/L; p = 0.02) and an increase in free T3 (+0.34 ± 0.15 pmol/L; p = 0.03); therefore, the free T3:free T4 ratio increased from 0.40 ± 0.02 to 0.47 ± 0.02 (p = 0.002). Sex hormone binding globulin (SHBG) level was unchanged. However, a decline in serum ferritin (−26.6 ± 8.5 ng/mL; p = 0.005) correlated with a fall in freeT4. Alterations in lipid profile, including a rise in large HDL sub-fractions and Lp (a) (+2.1 ± 21.1 nmol/L; p = 0.002) did not correlate with thyroid hormone levels. Significant increases were recorded in serum bone turnover markers - procollagen type 1 amino-terminal propeptide +57.4%; p = 0.0009, osteocalcin +48.6%; p = 0.0007; c-terminal telopeptides of type 1 collagen +73.7%; p = 0.002. Changes in bone formation markers occurred in parallel with fluctuations in thyroid hormone. ConclusionGH-induced alterations in the thyroid axis are associated with complex, tissue specific effects on thyroid hormone action. Modulation of bone turnover markers suggests that GH may improve the biological action of thyroid hormone on bone.

Genomics Analysis of Bacillus megaterium 1259 as a Probiotic and Its Effects on Performance in Lactating Dairy Cows.

Simple SummaryProbiotics play a vital role in animal production. Bacillus megaterium 1259, as a novel bacterium, has been used as a probiotic in poultry feed. In this study, we analyzed the genome sequence and genetic characteristics of Bacillus megaterium 1259 in order to have a deep understanding of its genomics information. Moreover, the effects of Bacillus megaterium 1259 as a probiotic on lactating dairy cow performance were determined due to the different digestive systems of dairy cows from poultry. The results suggest that Bacillus megaterium 1259 can increase milk production and will not bring any side effects on blood metabolites in dairy cows.In this study, we isolated a novel bacterium, Bacillus megaterium 1259 (BM1259), from chicken manure. Whole-genome sequencing analysis showed that the BM1259 complete genome is composed of a 5,043,095 bp circular chromosome and three circular plasmids, and it encodes 5379 coding genes and 182 RNA genes. Among these genes, a series of nitrate assimilation-related genes and pathways were identified, implying a potential role of BM1259 in nitrate metabolism. In addition, 24 lactating Holstein dairy cows were randomly assigned to four groups that were fed a total mixed ration (TMR) diet only (C), a TMR diet supplemented with 5 g/day of BM1259 (T1), a TMR diet supplemented with 10 g/day of BM1259 (T2), or a TMR diet supplemented with 15 g/day of BM1259 (T3). The results showed that supplementing dairy cows with 15 g/day of BM1259 increased 4% fat-corrected milk production. The molar proportion of propionate (C3) was significantly higher in T2 than in C. The C2:C3 ratio of T3 was higher than those of C and T2. No negative effect of BM1259 on blood indicators was detected. This study demonstrates BM1259 can be applied as a potential probiotic to improve nitrogen utilization and milk production in lactating dairy cows.

Misbalance of thyroid hormones after two weeks of exposure to artificial light at night in Eurasian perch Perca fluviatilis.

Artificial light at night (ALAN) can affect the physiology and behavior of animals because it alters the natural rhythm of light and darkness. Thyroid hormones (TH) are partially regulated by the light information of photoperiod and are involved in metabolic adjustments to daily and seasonal changes in the environment, such as larval and juvenile development, somatic growth and reproduction. ALAN can change photoperiodic information and might thereby lead to changes in thyroid metabolism, but so far research on this topic is scarce. Therefore, we tested in two different experiments the effects of nocturnal illumination at a wide range of light intensities on TH in plasma of Eurasian perch (Perca fluviatilis). Total 3,3',5-triiodo-L-thyronine (T3) was significantly affected by ALAN and reduced at the highest tested intensity of 100lx after only two weeks of exposure. Although total L-thyroxine (T4) was not significantly affected, the ratio of T3 to T4 tended to slightly decrease at 100lx. In a second low-light experiment ALAN did not have clear effects on T3, T4 or the ratio of T3 to T4 at intensities between 0.01lx and 1lx. The results show first signs of endocrine disruption in thyroid metabolism after a relatively short ALAN exposure of two weeks under high-intensity streetlight conditions. Misbalanced thyroidal status can have serious implications for metabolic rates as well as developmental and reproductive processes.

Thyroid function in patients with selenium deficiency exhibits high free T4 to T3 ratio.

.Selenium, one of the essential trace minerals, is present in vivo in form of selenoproteins. Iodothyronine deiodinase, a selenoprotein, is involved in the activation and inactivation of thyroid hormone. Therefore, patients with selenium deficiency may present changes in thyroid hormone levels due to inhibition of T4 to T3 conversion; however, this assumption is still under debate. In the present study, we retrospectively investigated the thyroid function in 22 patients with selenium deficiency. Thyroid stimulating hormone (TSH) and free T4 (FT4) levels were increased in 3 (14%) and 5 (23%) patients, respectively, and free T3 (FT3) levels were decreased in 6 (27%) patients. The FT4/FT3 ratio was significantly higher in patients with selenium deficiency than that in the control group. There appeared to be a positive correlation between the decreased rate of selenium levels and FT4/FT3 ratio, thereby indicating that patients with severe selenium deficiency also exhibited abnormal thyroid hormone levels. Furthermore, when selenium was supplemented in seven patients with abnormal thyroid hormone levels, the TSH, FT4, and FT4/FT3 ratio were significantly decreased and FT3 levels were increased. Collectively, patients with selenium deficiency could present the characteristics of not only low FT3 but also high FT4 and FT4/FT3 ratio.

T3:T4 Ratio Can Distinguish Between Adaptive Changes and True Subclinical Hypothyroidism in Older Adults

Because of heterogeneity in hormonal aging,1 we believe isolated elevated TSH is insufficient to drive clinical decision making for thyroid hormone replacement in older adults. We performed a cross-sectional study involving 63 older adult participants of the BLSA in order to assess the diagnostic value of individual hormone levels or free T3: free T4 ratio for differentiating thyroid-aging phenotypes. We defined two phenotypic groups, central adaptation and primary hypothyroidism, both with a rising TSH and with a rising or falling FT4 respectively. Fifty-four percent of study participants were male, the average age was 78.8 years, and 66.7% had the primary hypothyroidism phenotype. The unadjusted odds ratio of having the central adaptation phenotype is 23.40 (95% CI 3.66-149.73) for every unit increase in the FT3:FT4 ratio. The ROC curve had a C-statistic of 0.815. Similarly, FT4 alone distinguished the phenotypes with a C-statistic of 0.864. In contrast, TSH and FT3 were not predictive (C-statistic of 0.617, and 0.479 respectively). When the analysis is limited to the 24 individuals with elevated TSH, the ratio remains predictive (0.839). Both the higher FT4 and the lower ratio found in individuals with adaptive changes are consistent with a physiology similar to the adaptations seen in acute illness. This supports the hypothesis that elevated TSH can represent a response to stressors with aging and doesn’t always warrant treatment with thyroid hormone. Our findings suggest that full thyroid function panel can be used to make better diagnostic decisions in older adults.