The Effect of \u3cem\u3eLeucaena leucocephala\u3c/em\u3e on Beef Production and Toxicity in the Chaco Region of Argentina

Hedgerows of the fodder tree legume, Leucaena leucocephala (Lam.) de Wit ssp. glabrata (Rose Zárate) (leucaena), planted with companion grass, provide productive, profitable and sustainable tropical pasture (Shelton and Dalzell 2007). Although leucaena can improve beef production from tropical pastures, poor grower adoption has limited development of leucaena in the Chaco Region of Argentina. This can be partly attributed to: (1) unsuccessful establishment; (2) limited understanding of leucaena management as a forage resource; and (3) concerns about mimosine toxicity. These 3 limitations have been overcome in other regions of the world (e.g. northern Australia and the Chaco Region of Paraguay), but little is known about leucaena management and the protection status of ruminants against mimosine toxicosis in Argentina. The objective of this study was to evaluate the effect of leucaena on beef production and toxicity in the west of the Argentinean Chaco Region. We hypothesise that the introduction of leucaena into grass pastures will significantly increase beef productivity if mimosine toxicosis does not appear

Gender differences in V˙O2 and HR kinetics at the onset of moderate and heavy exercise intensity in adolescents

The majority of the studies on (V)over dotO(2) kinetics in pediatric populations investigated gender differences in prepubertal children during submaximal intensity exercise, but studies are lacking in adolescents. The purpose of this study was to test the hypothesis that gender differences exist in the (V)over dotO(2) and heart rate (HR) kinetic responses to moderate (M) and heavy (H) intensity exercise in adolescents. Twenty-one healthy African-American adolescents (9 males, 15.8 +/- 1.1 year; 12 females, 15.7 +/- 1 year) performed constant work load exercise on a cycle ergometer at M and H. The (V)over dotO(2) kinetics of the male group was previously analyzed (Lai et al., Appl. Physiol. Nutr. Metab. 33:107-117, 2008b). For both genders, (V)over dotO(2) and HR kinetics were described with a single exponential at M and a double exponential at H. The fundamental time constant (tau(1)) of (V)over dotO(2) was significantly higher in female than male at M (45 +/- 7 vs. 36 +/- 11 sec, P < 0.01) and H (41 +/- 8 vs. 29 +/- 9 sec, P < 0.01), respectively. The functional gain (G(1)) was not statistically different between gender at M and statistically higher in females than males at H: 9.7 +/- 1.2 versus 10.9 +/- 1.3 mL min(-1) W-1, respectively. The amplitude of the slow component was not significantly different between genders. The HR kinetics were significantly (tau(1), P < 0.01) slower in females than males at M (61 +/- 16 sec vs. 45 +/- 20 sec, P < 0.01) and H (42 +/- 10 sec vs. 30 +/- 8 sec, P = 0.03). The G(1) of HR was higher in females than males at M: 0.53 +/- 0.11 versus 0.98 +/- 0.2 bpm W-1 and H: 0.40 +/- 0.11 versus 0.73 +/- 0.23 bpm W-1, respectively. Gender differences in the (V)over dotO(2) and HR kinetics suggest that oxygen delivery and utilization kinetics of female adolescents differ from those in male adolescents

Industrial application of selected lactic acid bacteria isolated from local semolinas for typical sourdough bread production

Four obligate heterofermentative lactic acid bacteria (LAB) strains (Weissella cibaria PON10030 and PON10032 and Leuconostoc citreum PON 10079 and PON10080) were tested as single strain starters, mono-species dual strain starters, and multiple strain starter for the preparation and propagation of sourdoughs for the production of a typical bread at industrial level. The kinetics of pH and TTA during the daily sourdough refreshments indicated a correct acidification process for all trials. The concentration of lactic and acetic acid increased consistently during fermentation. The resulting molar ratios between these two organic acids in the experimental trials were lower than those observed in the control trial. The microbiological investigation showed levels of approximately 109 CFU/mL in almost all sourdoughs and the comparison of the genetic polymorphisms of the dominating LAB with those of the pure cultures evidenced the persistence of the added strains over time. The resulting breads were evaluated for several quality parameters. The breads with the greatest height were obtained with the quadruple combination of leuconostocs and weissellas. The highest softness was registered for the breads obtained from fermentations performed by W. cibaria PON10032 alone and in combination. The different inocula influenced also the color, the void fraction, the cell density and the mean cell area of the breads. Different levels of acids, alcohols, aldehydes, esters, hydrocarbons, ketones, terpenes, furans and phenol were emitted by the breads. The sensory tests indicated the breads from the sourdoughs fermented with the seven LAB inocula as sweeter and less acidic than control breads and the breads from the trials with the highest complexity of LAB inoculums were those more appreciated by tasters. A multivariate approach found strong differences among the trials. In particular, control breads and the breads obtained with different starter LAB were quite distant and a more strict relation was found among the productions carried out by W. cibaria strains. This study proved the suitability of the selected strains of L. citreum and W. cibaria for industrial-scale level applications in sourdough bread production

Mitochondrial leukoencephalopathy and complex II deficiency associated with a recessive SDHB mutation with reduced penetrance

Mitochondrial disease involving complex II is rare among respiratory chain deficiencies and its genetic cause remains often unknown. Two main clinical presentations are associated with this biochemical defect: mitochondrial encephalomyopathy and susceptibility to tumors. Only one homozygous SDHBmutation has been described in a patient with mitochondrial disorder. We report here two sisters, who presented highly different phenotypes (neurological impairmentwith leukoencephalopathy vs. asymptomatic status) and harbored the same homozygous SDHB mutation, suggesting reduced penetrance

Functionally pathogenic EARS2 variants in vitro may not manifest a phenotype in vivo

OBJECTIVE: To investigate the genetic etiology of a patient diagnosed with leukoencephalopathy, brain calcifications, and cysts (LCC). METHODS: Whole-exome sequencing was performed on a patient with LCC and his unaffected family members. The variants were subject to in silico and in vitro functional testing to determine pathogenicity. RESULTS: Whole-exome sequencing uncovered compound heterozygous mutations in EARS2, c.328G>A (p.G110S), and c.1045G>A (p.E349K). This gene has previously been implicated in the autosomal recessive leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL). The p.G110S mutation has been found in multiple patients with LTBL. In silico analysis supported pathogenicity in the second variant. In vitro functional testing showed a significant mitochondrial dysfunction demonstrated by an ∼11% decrease in the oxygen consumption rate and ∼43% decrease in the maximum respiratory rate in the patient's skin fibroblasts compared with the control. EARS2 protein levels were reduced to 30% of normal controls in the patient's fibroblasts. These deficiencies were corrected by the expression of the wild-type EARS2 protein. However, a further unrelated genetic investigation of our patient revealed the presence of biallelic variants in a small nucleolar RNA (SNORD118) responsible for LCC. CONCLUSIONS: Here, we report seemingly pathogenic EARS2 mutations in a single patient with LCC with no biochemical or neuroimaging presentations of LTBL. This patient illustrates that variants with demonstrated impact on protein function should not necessarily be considered clinically relevant.Funding provided by the Baylor Scott & White Healthcare Foundation

Survey of overnight academic hospitalist supervision of trainees

In 2003, Accreditation Council for Graduate Medical Education (ACGME) announced the first in a series of guidelines related to the residency training. The most recent recommendations include explicit recommendations regarding the provision of on‐site clinical supervision for trainees of internal medicine. To meet these standards, many internal medicine residency programs turned to hospitalist programs to fill that need. However, much is unknown about the current relationships between hospitalist and residency programs, specifically with regard to supervisory roles and supervision policies. We aimed to describe how academic hospitalists currently supervise housestaff during the on‐call, or overnight, period and hospitalist program leader their perceptions of how these new policies would impact trainee‐hospitalist interactions. Journal of Hospital Medicine 2012; © 2012 Society of Hospital MedicinePeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93713/1/1961_ftp.pd

Not only dominant, not only optic atrophy: expanding the clinical spectrum associated with OPA1 mutations

Background: Heterozygous mutations in OPA1 are a common cause of autosomal dominant optic atrophy, sometimes associated with extra-ocular manifestations. Few cases harboring compound heterozygous OPA1 mutations have been described manifesting complex neurodegenerative disorders in addition to optic atrophy. Results: We report here three patients: one boy showing an early-onset mitochondrial disorder with hypotonia, ataxia and neuropathy that was severely progressive, leading to early death because of multiorgan failure; two unrelated sporadic girls manifesting a spastic ataxic syndrome associated with peripheral neuropathy and, only in one, optic atrophy. Using a targeted resequencing of 132 genes associated with mitochondrial disorders, in two probands we found compound heterozygous mutations in OPA1: in the first a 5 nucleotide deletion, causing a frameshift and insertion of a premature stop codon (p.Ser64Asnfs*7), and a missense change (p.Ile437Met), which has recently been reported to have clinical impact; in the second, a novel missense change (p.Val988Phe) co-occurred with the p.Ile437Met substitution. In the third patient a homozygous mutation, c.1180G > A (p.Ala394Thr) in OPA1 was detected by a trio-based whole exome sequencing approach. One of the patients presented also variants in mitochondrial DNA that may have contributed to the peculiar phenotype. The deleterious effect of the identified missense changes was experimentally validated in yeast model. OPA1 level was reduced in available patients\u2019 biological samples, and a clearly fragmented mitochondrial network was observed in patients\u2019 fibroblasts. Conclusions: This report provides evidence that bi-allelic OPA1 mutations may lead to complex and severe multi-system recessive mitochondrial disorders, where optic atrophy might not represent the main feature

Clinical-genetic features and peculiar muscle histopathology in infantile DNM1L-related mitochondrial epileptic encephalopathy

Mitochondria are highly dynamic organelles, undergoing continuous fission and fusion. The DNM1L gene encodes for the DRP1 protein, an evolutionary conserved member of the dynamin family, responsible for fission of mitochondria, and having a role in the division of peroxisomes, as well. DRP1 impairment is implicated in several neurological disorders and associated with either de novo dominant or compound heterozygous mutations. In five patients presenting with severe epileptic encephalopathy we identified 5 de novo dominant DNM1L variants, the pathogenicity of which was validated in a yeast model. Fluorescence microscopy revealed abnormally elongated mitochondria and aberrant peroxisomes in mutant fibroblasts, indicating impaired fission of these organelles. Moreover, a very peculiar finding in our cohort of patients was the presence, in muscle biopsy, of core like areas with oxidative enzyme alterations, suggesting an abnormal distribution of mitochondria in the muscle tissue

ATPase Domain AFG3L2 Mutations Alter OPA1 Processing and Cause Optic Neuropathy

Objective: Dominant optic atrophy (DOA) is the most common inherited optic neuropathy, with a prevalence of 1:12,000 to 1:25,000. OPA1 mutations are found in 70% of DOA patients, with a significant number remaining undiagnosed. Methods: We screened 286 index cases presenting optic atrophy, negative for OPA1 mutations, by targeted next generation sequencing or whole exome sequencing. Pathogenicity and molecular mechanisms of the identified variants were studied in yeast and patient-derived fibroblasts. Results: Twelve cases (4%) were found to carry novel variants in AFG3L2, a gene that has been associated with autosomal dominant spinocerebellar ataxia 28 (SCA28). Half of cases were familial with a dominant inheritance, whereas the others were sporadic, including de novo mutations. Biallelic mutations were found in 3 probands with severe syndromic optic neuropathy, acting as recessive or phenotype-modifier variants. All the DOA-associated AFG3L2 mutations were clustered in the ATPase domain, whereas SCA28-associated mutations mostly affect the proteolytic domain. The pathogenic role of DOA-associated AFG3L2 mutations was confirmed in yeast, unraveling a mechanism distinct from that of SCA28-associated AFG3L2 mutations. Patients' fibroblasts showed abnormal OPA1 processing, with accumulation of the fission-inducing short forms leading to mitochondrial network fragmentation, not observed in SCA28 patients' cells. Interpretation: This study demonstrates that mutations in AFG3L2 are a relevant cause of optic neuropathy, broadening the spectrum of clinical manifestations and genetic mechanisms associated with AFG3L2 mutations, and underscores the pivotal role of OPA1 and its processing in the pathogenesis of DOA. ANN NEUROL 2020