Locomotor-like rhythms in a genetically distinct cluster of interneurons in the mammalian spinal cord

Electrophysiological and morphological properties of genetically identified spinal interneurons were examined to elucidate their possible contribution to locomotor-like rhythmic activity in 1- to 4-day-old mice. In the transgenic mice used in our study, the HB9 promotor controlled the expression of the reporter gene enhanced green fluorescent protein (eGFP), giving rise to GFP+ motoneurons and ventral interneurons. However, only motoneurons and a small group of bipolar, GFP+ interneurons expressed the HB9 protein. The HB9(+)/GFP+ interneurons were clustered close to the medial surface in lamina VIII along segments L1-L3. The correlation between activity pattern in these visually identified interneurons and motoneuron output was examined using simultaneous whole cell and ventral root recordings. Neurochemically induced rhythmic membrane depolarizations in HB9/GFP interneurons were synchronous with ventral root rhythms, indicating that the interneurons received synaptic inputs from rhythm-generating networks. The frequency of excitatory postsynaptic currents significantly increased during ventral root bursts, but there was no change in the frequency of inhibitory postsynaptic currents during the cycle period. These data implied that HB9/GFP interneurons received primarily excitatory inputs from rhythmogenic interneurons. Neurobiotin-filled axon terminals were in close apposition to other neurons in the cluster and to motoneuron dendrites, raising the possibility that HB9/GFP interneurons formed synaptic connections with each other and with motoneurons. The expression of the vesicular glutamate transporter 2 in axon terminals of HB9/GFP interneurons indicated that these were glutamatergic interneurons. Our findings suggest that the visually identified HB9/GFP interneurons are premotor excitatory interneurons and putative constituents of networks generating locomotor rhythms in the mammalian spinal cord.     

How to find a mutation behind an inherited disease

The search for the mutations causing human diseases is reaching new gene areas with increasing speed with new cloned genes or polymorphic gene areas, being reported every week. The almost 300 cloned genes and over 1000 RFLP-loci of the human genome can be used as tools to approach most human gene defects. Once the linkage between the disease and the RFLP has been found, chromosomal "jumping" or pulsed field electrophoresis can be used to separate the DNA areas in the neighbourhood of the first found RFLP locus for more detailed studies and finally for the location of the defective gene. Once found, the detailed analysis of gene mutations still requires the use of several, technically very demanding approaches of molecular biology. New techniques, such as the multiplication of the required gene area in a test tube as well as RNase protection assays have been used successfully to pick out about 80-90% of the mutations which occur in one gene area and cause the disease of this gene area. The increased specificity and sensitivity of these modern approaches do not, however, necessarily lead to the rapid diagnosis of all inherited diseases. Even once a linkage has been established between RFLP locus and a disease the path is still a long one: as demonstrated in Duchenne's muscular dystrophy and Huntington's disease, we have diagnostic RFLP-linkages but the search for the gene defect continues. Further, the increased sensitivity of the mutation assays will eventually reveal all the variations in an individual.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ghrelin and Glucagon-Like Peptide-1: A Gut-Brain Axis Battle for Food Reward

Eating behaviors are influenced by the reinforcing properties of foods that can favor decisions driven by reward incentives over metabolic needs. These food reward-motivated behaviors are modulated by gut-derived peptides such as ghrelin and glucagon-like peptide-1 (GLP-1) that are well-established to promote or reduce energy intake, respectively. In this review we highlight the antagonizing actions of ghrelin and GLP-1 on various behavioral constructs related to food reward/reinforcement, including reactivity to food cues, conditioned meal anticipation, effort-based food-motivated behaviors, and flavor-nutrient preference and aversion learning. We integrate physiological and behavioral neuroscience studies conducted in both rodents and human to illustrate translational findings of interest for the treatment of obesity or metabolic impairments. Collectively, the literature discussed herein highlights a model where ghrelin and GLP-1 regulate food reward-motivated behaviors via both competing and independent neurobiological and behavioral mechanisms.     

Machine Learning Algorithms to Predict Mortality and Allocate Palliative Care for Older Patients With Hip Fracture

ObjectivesTo evaluate a machine learning model designed to predict mortality for Medicare beneficiaries aged >65 years treated for hip fracture in Inpatient Rehabilitation Facilities (IRFs).DesignRetrospective design/cohort analysis of Centers for Medicare & Medicaid Services Inpatient Rehabilitation Facility–Patient Assessment Instrument data.Setting and ParticipantsA total of 17,140 persons admitted to Medicare-certified IRFs in 2015 following hospitalization for hip fracture.MeasuresPatient characteristics include sociodemographic (age, gender, race, and social support) and clinical factors (functional status at admission, chronic conditions) and IRF length of stay. Outcomes were 30-day and 1-year all-cause mortality. We trained and evaluated 2 classification models, logistic regression and a multilayer perceptron (MLP), to predict the probability of 30-day and 1-year mortality and evaluated the calibration, discrimination, and precision of the models.ResultsFor 30-day mortality, MLP performed well [acc = 0.74, area under the receiver operating characteristic curve (AUROC) = 0.76, avg prec = 0.10, slope = 1.14] as did logistic regression (acc = 0.78, AUROC = 0.76, avg prec = 0.09, slope = 1.20). For 1-year mortality, the performances were similar for both MLP (acc = 0.68, AUROC = 0.75, avg prec = 0.32, slope = 0.96) and logistic regression (acc = 0.68, AUROC = 0.75, avg prec = 0.32, slope = 0.95).Conclusion and ImplicationsA scoring system based on logistic regression may be more feasible to run in current electronic medical records. But MLP models may reduce cognitive burden and increase ability to calibrate to local data, yielding clinical specificity in mortality prediction so that palliative care resources may be allocated more effectively.     

Impact of COVID-19 Among Immigrant and Communities of Color Living with HIV in Oregon, 2020: Two Pandemics Rooted in Racism

Journal of Immigrant and Minority Health - Over 8100 people living with HIV (PLWH) in Oregon are at risk of acquiring COVID-19, and communities of color are disproportionately impacted by both...     

Growth control of human mammary cancer cells (MCF-7 cells) in culture: effect of estradiol and growth factors in serum-containing medium

The growth control of estrogen-dependent mammary cancer is very complex and only partly understood. The present study was undertaken in order to establish conditions for growth control of MCF-7 cells in monolayer culture with focus on the effect of estradiol-17 beta, fetal calf serum, and growth factors. The effect of charcoal-stripped fetal calf serum (CSFCS) on cell growth was dependent upon the presence of hormones or growth factors in the medium. In the presence of insulin (or insulin-like growth factor 1) and in the absence of estradiol-17 beta, increasing concentrations of CSFCS, 0.625-20%, produced a bell-shaped growth response curve. Serum concentrations greater than 2.5% inhibited cell growth in the absence of estradiol-17 beta, whereas CSFCS in a dose-dependent way up to 10% stimulated growth in the presence of estradiol-17 beta (5 x 10(-10) mol/liter). The growth inhibitory effect of CSFCS could not be demonstrated in the absence of insulin (or insulin-like growth factor 1) and estradiol-17 beta. CSFCS stimulated growth in a dose-dependent way in the presence of estradiol-17 beta and also in the absence of insulin. Both the putative growth inhibitor and stimulator were found to be heat stable and not dialyzable. Epidermal growth factor stimulated growth but was unable to eliminate the growth inhibitory effect of 5-10% CSFCS. Interleukin-1 alpha inhibited MCF-7 cell growth in a dose-dependent way and produced a 75% reduction in cell number at a concentration of 5 x 10(-10) mol/liter. This inhibition was almost totally overcome by estradiol-17 beta. It is concluded that serum appears to contain factors with both stimulatory and inhibitory effects on the growth of MCF-7 cells. The inhibitory effect can be eliminated by estradiol (5 x 10(-10) mol/liter). In the presence of estradiol cell growth is stimulated by CSFCS in a dose-related way up to 5-10%. Taken together these data seem to indicate that estradiol stimulates cell growth in two principal ways: partly by eliminating the effect of an inhibitor, in support of a "negative hypothesis," and partly by an effect whereby estradiol permits a growth stimulator in CSFCS to be expressed, in support of the "indirect positive hypothesis."     

Poor survival of cementless Biomet total hip: a report on 1,047 hips from the Finnish Arthroplasty Register

In Finland, almost 50% of all hip replacements done after 1989 have been inserted without cement. Biomet components have been the most commonly used implants in cementless arthroplasties. Between 1985 and 1997, 4,300 prostheses were implanted because of primary osteoarthrosis. 4 different acetabular component designs have been identified as Biomet implants (Mallory-Head, Romanus, T-TAP, Universal) and were used in 1,047 hips. The 9-year survival of all arthroplasties using Biomet cups was only 65 (95% CI 61-69)% while that of arthroplasties using T-TAP-cups was only 58 (52-65)%. In contrast, the 7.5-year survival of arthroplasties using Romanus cups was 85 (79-91)%. The 98 (96-99)% 5-year survival of arthroplasties with Mallory-Head cups should be interpreted cautiously, since similar results of arthroplasties using the Universal cup with the same type of liner decline sharply to 93 (88-98)% only 1 year later. The poor survival of Biomet cementless prostheses in our series seems to be related to the poor survival of the cup. This finding was common to all metal shell designs using Hexloc liners. We recommend that Biomet cups with Hexloc liners should not be used and patients who have had them inserted should undergo regular clinical and radiographic follow-ups.     

Local lymph node assay responses to paraphenylenediamine: intra- and inter-laboratory evaluations.

The murine local lymph node assay (LLNA) is a method for the prospective identification of skin sensitizing chemicals. Proliferative responses induced in lymph nodes draining the site of topical application of the test chemical are measured and those chemicals that induce a stimulation index of three or more compared with concurrent vehicle-treated controls are considered to have the potential to cause skin sensitization. Dose-response data from the LLNA may be used to derive an estimate of relative skin sensitizing potency, based upon derivation of the concentration of chemical required to cause a stimulation index of 3 (EC3 value) as calculated by linear interpolation. The purpose of the present investigations was to examine the stability of LLNA responses and the consistency of derived EC3 values induced by the contact allergen paraphenylenediamine (PPD). Analyses were conducted once a month over a 4-month period in each of two independent laboratories. In all assays, and in both laboratories, PPD elicited a positive response. Although some minor differences in responses between and within laboratories were observed, the derived EC3 values were generally very consistent. In Laboratory 1, EC3 values varied between 0.06 and 0.09% PPD, whereas in Laboratory 2 the range was 0.09-0.20%. These EC3 values are consistent with clinical experience of this material insofar as it is a common and relatively potent cause of allergic contact dermatitis in humans. Taken together, these data confirm the stability of LLNA responses both with time and between laboratories and provide additional support for the use of derived EC3 values in the assessment of relative skin sensitizing potency.     

Effects of eating an uncooked vegetable diet for 1 week

Biochemical and metabolic indicators were monitored in a group of volunteers suffering from a variety of chronic illnesses participating in a week's course on a special uncooked vegetable diet, known as "living food". Unmatched healthy controls ate the same diet cooked for 2 min in a microwave oven. After 1 week on the regimen, serum protein and urea contents decreased and alanine aminotransferase (ALAT) activity increased in both groups, although all within the normal range. Blood glucose increased in both groups to slightly above normal limits but total serum cholesterol dropped about 1 mmol/l from normal starting levels. Serum tocopherol and retinol increased only in the group eating the uncooked diet. In both groups urinary sodium dropped drastically without a significant change in potassium. Serum and urinary phenol and p-cresol diminished also significantly. It is concluded that this vegetable diet may be of some benefit in the short term but any longer-term use requires evaluation.