Introduction: Inborn errors of metabolism (IEM) are a rare cause of epilepsy in pediatric age group. Prompt diagnosis is essential, as some of these disorders are treatable. Aim: To determine the ...prevalence, clinical, and etiological profile of metabolic epilepsy in children. Methods: A prospective observational study of children with new onset seizures diagnosed as inherited metabolic disorder in a tertiary care hospital, South India. Results: Among 10,778 children with new onset seizures, 63 (0.58%) had metabolic epilepsy. The male female ratio was 1.3:1. Onset of the seizures were in neonatal period in 12 (19%), infancy in 35 (55.6%), and between one and 5 years of age in 16 (25.4%) children. Generalised seizures were seen in 46 (73%), followed by multiple seizure types (31.7%). The associated clinical features included developmental delay in 37 (58.7%), hyperactivity in 7 (11%), microcephaly in 13 (20.6%), optic atrophy in 12 (19%), sparse hair and/or seborrheic dermatitis in 10 (15.9%), movement disorder in 7 (11%), and focal deficit in 27 (42.9%) patients. Magnetic resonance imaging brain was abnormal in 44 (69.8%) and diagnostic in 28 (44.4%) patients. Causative metabolic errors included vitamin responsive errors in 20 (31.7%), disorders of complex molecules in 13 (20.6%), amino acidopathies in 12 (19%), organic acidemias in 10 (16%), disorders of energy metabolism in 6 (9.5%), and peroxisomal disorders in 2 (3.2%) patients. With specific treatment, seizure freedom could be achieved in 45 (71%) children. Five children lost to follow-up and two died. Among the remaining 56 patients, 11 (19.6%) had a good neurological outcome. Conclusion: Vitamin responsive epilepsies were the most frequent cause of metabolic epilepsy. Early diagnosis and prompt treatment is necessary as only one-fifth had a good neurological outcome.
Significance Cyclic electron flow around photosystem I (CEF) is critical for balancing the energy budget of photosynthesis, but its regulation is not well understood. Our results provide evidence ...that hydrogen peroxide, which is produced as a result of imbalances in chloroplast redox state, acts as a signaling agent to activate CEF in higher plants in vivo.
Cyclic electron flow (CEF) around photosystem I is thought to balance the ATP/NADPH energy budget of photosynthesis, requiring that its rate be finely regulated. The mechanisms of this regulation are not well understood. We observed that mutants that exhibited constitutively high rates of CEF also showed elevated production of H ₂O ₂. We thus tested the hypothesis that CEF can be activated by H ₂O ₂ in vivo. CEF was strongly increased by H ₂O ₂ both by infiltration or in situ production by chloroplast-localized glycolate oxidase, implying that H ₂O ₂ can activate CEF either directly by redox modulation of key enzymes, or indirectly by affecting other photosynthetic processes. CEF appeared with a half time of about 20 min after exposure to H ₂O ₂, suggesting activation of previously expressed CEF-related machinery. H ₂O ₂-dependent CEF was not sensitive to antimycin A or loss of PGR5, indicating that increased CEF probably does not involve the PGR5-PGRL1 associated pathway. In contrast, the rise in CEF was not observed in a mutant deficient in the chloroplast NADPH:PQ reductase (NDH), supporting the involvement of this complex in CEF activated by H ₂O ₂. We propose that H ₂O ₂ is a missing link between environmental stress, metabolism, and redox regulation of CEF in higher plants.
ABSTRACT
The occurrence of wooden breast (WB) and white striping (WS) of broiler breast myopathies may be associated with least-cost feed formulations and the inclusion of greater amounts of ...synthetic amino acids. Two experiments were conducted to evaluate the effects of supplemental glutamine (Gln-/+, 0 and 1%) and arginine (Arg-/+, 0 and 0.25%) in a 2 × 2 factorial arrangement. Experiment 1 consisted of 8 replicates using 32 pens and focused on live performance to 44 d of age, carcass yield, and meat quality evaluations at 45 d of age. Live performance parameters including feed intake, BW gain, mortality, and feed conversion were evaluated. Post-harvest carcass yield, breast muscle quality (including WB and WS), proximate analysis, and mineral analysis of breast muscle and tibia bone were also evaluated. Experiment 2 comprised 4 replicates using 8 pens with weekly measurements of blood physiology and muscle myopathy development from 21 to 45 d of age. Broilers fed supplemental Gln and Arg (Gln+/Arg+) produced broilers with greater BW and improved FCR. The WB and WS severity increased with Gln+ diets, while only WB increased using Arg+ diets. Weekly observations revealed the greatest increase in WB myopathies occurred between 28 to 35 d, while WS significantly increased one week later (35 to 42 d). When comparing broilers of similar BW at 45 d, Gln+ diets resulted in greater WS scores and percentage breast muscle fat. Further analysis of WB and WS scores (independent of treatment affect) revealed that increased myopathy scores were associated with increased blood CO2, H2CO3, and reduced O2 with increased meat pH, moisture content, and Ca concentration. These results indicated that increased muscle Ca is associated with increased WB, while increased dietary glutamine and lack of oxygen may have resulted in a reverse flux of the citric acid cycle and reduced electron transport chain activity resulting in increased WS.
The objective of this experiment was to investigate the effects of various dietary concentrations of vitamin D3 (D3) on pullet and laying hen performance, eggshell quality, bone health, and yolk D3 ...content from day of hatch until 68 wk of age. Initially, 440 Hy-line W36-day-old chicks were randomly assigned to 5 dietary treatments: 1,681 (control); 8,348; 18,348; 35,014; 68,348 IU D3/kg. At 17 wk of age, pullets were assigned to experimental diets with 12 replicate groups of 6 birds. At 17 wk of age, pullets fed diets containing 8,348 and 35,014 IU D3/kg had an increased bone mineral density in comparison to the control fed birds (P ≤ 0.01). Body weights of pullets fed the diet with 68,348 IU D3/kg were lower than other treatments (P ≤ 0.01). Hen-housed egg production (HHEP) of hens fed the 35,014 IU D3/kg diet was increased in comparison to control-fed hens (P ≤ 0.01), whereas HHEP of those fed 68,348 IU D3/kg diet was reduced in comparison to all other treatments (P ≤ 0.01). Shell breaking strength of eggs from hens fed 8,348, 35,014 and 68,348 IU D3/kg was increased in comparison to eggs from control-fed birds (P ≤ 0.01). Fat-free tibia ash content of hens fed any of the diets supplemented with D3 (8,348 to 68,348 IU D3/kg) was increased in comparison to control-fed hens (P ≤ 0.05). Yolk D3 content increased linearly with dietary D3 and the D3 transfer efficiency for the control, 8,348 IU, 18,348 IU, 35,014 IU, and 68,348 IU D3 treatments were 8.24, 10.29, 11.27, 12.42, and 12.06%, respectively. These data suggest that supplementation of dietary D3 up to 35,014 IU D3/kg feed maintained if not increased laying hen performance and enhanced pullet and laying hen skeletal quality as well as yolk D3 content and eggshell quality. Feeding pullets at a higher level 68,348 IU of D3 resulted in reduced growth and ultimately decreased performance of laying hens.
A total of 960 male Cobb 500 broilers were used in a growth performance study to explore the effect of coccidial vaccination and/or coccidial challenge on blood biochemistry and veterinary postmortem ...metrics. Day-old chicks were randomly divided into one of the 4 experimental treatments. Treatments were arranged in a 2 × 2 factorial arrangement, with the factors being without or with vaccination (administered on day 1) or coccidial challenge (oral gavage on day 7). Growth performance was monitored on a weekly basis. Blood sample collection, as well as full veterinary necropsies, were carried out on days 6, 8, 13, 20, 27, and 34. Birds that did not receive the vaccination but were challenged with coccidiosis had higher feed conversion ratio, lower body weights, and higher mortality than the other experimental groups, and this effect was particularly evident from day 13 to day 20. Birds challenged with coccidiosis had lower plasma sodium and total carotenoid concentrations and higher potassium and globulin concentrations than nonchallenged birds. Significant interactions between age and experimental treatment for these blood parameters were observed, particularly on day 13. The necropsy results confirmed the effectiveness of the challenge and vaccination treatments, wherein birds that were challenged had higher coccidiosis scores on day 13 and day 27 than birds that were not challenged. These results demonstrate the potential for plasma sodium, potassium, total protein, total carbon dioxide, globulin, and carotenoid analysis for early diagnosis of coccidiosis in growing broiler chickens. Further work is necessary to establish whether the changes in blood biochemistry observed in the present study are transferable to alternative flocks of chicken and whether early diagnosis and intervention may mitigate performance losses associated with this disease.
Abstract At the Electron Ion Collider, quasi-real photoproduction measurements involve tracking scattered electrons at small angles relative to the beamline. These electrons act as effective beams of ...tagged almost-real photons, with a high flux compared to larger Q 2 interactions. However, the proximity of the detector to the electron beam results in a very high flux of electrons from the bremsstrahlung process (about 10 electrons per 12 ns electron/ion bunch crossing over an area of approximately 100 cm 2 ). Consequently, the tracking detector systems experience high occupancy. To address this, we propose using machine learning algorithms, specifically object condensation methods, which excel at track building in the quasi-real photon tagger. These algorithms achieve track finding efficiency of 95% or higher and purity of 90% or higher, even in the presence of noise and hit detection inefficiencies.
Broiler dietary potassium (K) and available phosphorous (AvP) have decreased in recent years but both ions are intimately involved in the elimination of hydrogen ions that are produced during rapid ...growth. It was hypothesized that the decrease of these dietary electrolytes was related to the development of myopathies, and thus increased dietary K and/or AvP would reduce the occurrence of breast myopathies. A total of 320 Ross male broiler chicks were placed into 16 pens and fed 2 diet series containing either decreasing AvP levels of 0.45, 0.40, and 0.35% in the starter, grower, and finisher diets, respectively (Decline), or a fixed AvP of 0.45% in all dietary phases (Fixed). To complete a 2 × 2 design either normal basal dietary K (K-) (0.86, 0.77, 0.68%) or added dietary K (K+) (1.01, 0.93, 0.88%) were also applied to starter, grower, and finisher diets, respectively. Blood physiology was measured at 29 and 42 d. Carcass data, wooden breast and white striping scores were measured at 35 and 43 d. The K+ diets improved feed conversion ratio at 35 d (1.52 vs 1.57 g: g), reduced body weight at 42 d (3524 vs 3584 g), reduced hemoglobin (6.83 vs 7.58 g/dL), and packed cell volume (20.1 vs 22.3%) at 29 d, reduced ionized blood calcium (1.42 vs 1.47 mmol/L) at 42 d, and reduced partial pressure of blood CO2 (49.1 vs 54.7 mm/Hg) at 42 d relative to broilers fed basal K- diets (P < 0.05). Fixed AvP diets improved feed conversion ratio at 28 and 42 d, increased percentage breast meat (28.85 vs 27.58%) and carcass water pickup (2.72 vs 1.42%) at 35 d, and reduced wooden breast (2.88 vs 3.69) at 43 d (P < 0.05).
The estrogen receptor (ER) regulates the survival and growth of breast cancer cells, but it is less clear how components of the tissue microenvironment affect ER-mediated responses. We set out to ...test how human mammary fibroblasts (HMFs) modulate ER signaling and downstream cellular responses. We exposed an organotypic mammary model consisting of a collagen-embedded duct structure lined with MCF7 cells to 17-β estradiol (E2), with and without HMFs in the surrounding matrix. MCF7 cells grown as ductal structures were polarized and proliferated at rates comparable to in vivo breast tissue. In both culture platforms, exposure to E2 increased ER transactivation, increased proliferation, and induced ductal hyperplasia. When the surrounding matrix contained HMFs, the onset and severity of E2-induced ductal hyperplasia was increased due to decreased apoptosis. The reduced apoptosis may be due to fibroblasts modulating ER signaling in MCF7 cells, as suggested by the increased ER transactivation and reduced ER protein in MCF7 cells grown in co-culture. These findings demonstrate the utility of organotypic platforms when studying stromal:epithelial interactions, and add to existing literature that implicate the mammary microenvironment in ER + breast cancer progression.
Constitutive activation of the JAK/STAT3 pathway is a major contributor to oncogenesis. In the present study, structure-activity relationship (SAR) studies with five cucurbitacin (Cuc) analogs, A, B, ...E, I, and Q, led to the discovery of Cuc Q, which inhibits the activation of STAT3 but not JAK2; Cuc A which inhibits JAK2 but not STAT3 activation; and Cuc B, E, and I, which inhibit the activation of both. Furthermore, these SAR studies demonstrated that conversion of the C3 carbonyl of the cucurbitacins to a hydroxyl results in loss of anti-JAK2 activity, whereas addition of a hydroxyl group to C11 of the cucurbitacins results in loss of anti-STAT3 activity. Cuc Q inhibits selectively the activation of STAT3 and induces apoptosis without inhibition of JAK2, Src, Akt, Erk, or JNK activation. Furthermore, Cuc Q induces apoptosis more potently in human and murine tumors that contain constitutively activated STAT3 (i.e., A549, MDA-MB-435, and v-Src/NIH 3T3) as compared to those that do not (i.e., H-Ras/NIH 3T3, MDA-MB-453, and NIH 3T3 cells). Finally, in a nude mouse tumor xenograft model, Cuc Q, but not Cuc A, suppresses tumor growth indicating that JAK2 inhibition is not sufficient to inhibit tumor growth and suggesting that the ability of Cuc Q to inhibit tumor growth is related to its anti-STAT3 activity. These studies further validate STAT3 as a drug discovery target and provide evidence that pharmacological agents that can selectively reduce the P-STAT3 levels in human cancer cells result in tumor apoptosis and growth inhibition.
A total of 640 broilers were used to determine the effects of strain, sex, and age on hematology and blood chemistry using rapid detection devices. Day old chicks from two genetic lines of common ...fast-growing and high-yield broiler strains were sexed and allocated to 40 pens (16 birds per pen) containing either male or female and Ross or Cobb strains (n = 10). Venous blood was analyzed weekly using 2 broilers from each pen (n = 20) using the i-STAT® Alinity Handheld Clinical Analyzer, Zoetis Vetscan VS2, and iCheck™ Carotene devices at 14, 21, 28, 35, and 42 d, as well as growth performance. Post-mortem health tracking metrics were also recorded on 42 d. Broilers were deemed healthy based on posting data results and performed in accordance with industry standards with males presenting greater BW and reduced FCR than female broilers. Ross broilers displayed greater BW to 14 d with similar FCR compared with Cobb birds. Day of age had a highly significant impact on blood calcium, phosphorus, potassium, sodium, chloride, carotene, aspartate aminotransferase, creatine kinase, bile acids, uric acid, total protein, albumin, globulin, total carbon dioxide, hematocrit, and malondialdehyde. Male broilers had reduced blood sodium, chloride, carotene, uric acid, albumin, and increased total protein, glucose, and total carbon dioxide. Ross broilers had greater blood potassium, and sodium, as well as reduced uric acid, total protein, globulin, and malondialdehyde, compared with Cobb birds. These results demonstrated the effectiveness of point-of-care devices in measuring blood chemistry and hematology in modern broilers. These data can be utilized to determine normal healthy blood ranges in these types of broilers when accounting for strain, sex, and age.
Broiler, Biomarkers, Blood physiology, Rapid point-of-care detection, Animal breeding, Animal product, Biochemistry, Animal physiology, Veterinary science.