Microbial transmission in the social microbiome and host health and disease.

Although social interactions are known to drive pathogen transmission, the contributions of socially transmissible host-associated mutualists and commensals to host health and disease remain poorly explored. We use the concept of the social microbiome-the microbial metacommunity of a social network of hosts-to analyze the implications of social microbial transmission for host health and disease. We investigate the contributions of socially transmissible microbes to both eco-evolutionary microbiome community processes (colonization resistance, the evolution of virulence, and reactions to ecological disturbance) and microbial transmission-based processes (transmission of microbes with metabolic and immune effects, inter-specific transmission, transmission of antibiotic-resistant microbes, and transmission of viruses). We consider the implications of social microbial transmission for communicable and non-communicable diseases and evaluate the importance of a socially transmissible component underlying canonically non-communicable diseases. The social transmission of mutualists and commensals may play a significant, under-appreciated role in the social determinants of health and may act as a hidden force in social evolution.

Effect of osteoarthritis on the repeatability of patella tendon angle measurement in dogs.

OBJECTIVE: To evaluate the influence of osteoarthritis on the measurement of patella tendon angle (PTA) and determine intraobserver and interobserver variability. STUDY DESIGN: Retrospective clinical study. SAMPLE POPULATION: Eighty-seven mediolateral radiographs that were obtained prior to tibial tuberosity advancement. METHODS: Radiographic osteoarthritis was scored by 2 observers using guidelines derived from the International Elbow Working Group Protocol. Patella tendon angle was measured by 3 observers on 3 occasions, with at least 7 days between measurements. The data were statistically analyzed via weighted κ and Kruskal-Wallis testing. RESULTS: A fair strength of agreement was found among observers scoring osteoarthritis, with the same grades in 48% of radiographs. The intraobserver average bias between PTA measurements 1 and 3 ranged from -0.38° to -0.94°. Interobserver bias in angle measurement ranged from -0.92° to -2.00°. Observer 1 had the narrowest range of PTA differences (12.1°), and observer 3 had the highest range of PTA differences (23.5°). Observer 2 had the lowest mean bias (-0.38°). The mean bias was lowest between observers 1 and 2 (-0.92°) and highest between observers 1 and 3 (-2.0°). The mean intraobserver standard deviation of the PTA measurement differences was 2.90°, and interobserver standard deviation of the PTA measurement differences was 2.26°. The degree of osteoarthritis did not influence PTA measurements or their variability. CONCLUSION: The current study did not find evidence of an influence of osteoarthritis on PTA or on the repeatability of measurements. CLINICAL SIGNIFICANCE: Our findings suggest that osteoarthritis should not affect the radiographic planning for tibial tuberosity advancement surgery. The high variances in PTA measurement in less experienced observers may influence the clinical outcome of surgery.

Activation of the caspase 8 pathway mediates seizure-induced cell death in cultured hippocampal neurons.

In response to harmful stresses, cells induce programmed cell death (PCD) or apoptosis. Seizures can induce neural damage and activate biochemical pathways associated with PCD. Since seizures trigger intracellular calcium overload, it has been presumed that the intrinsic cell death pathway mediated by mitochondrial dysfunction would modulate cell death following seizures. However, previous work suggests that the extrinsic cell death pathway may initiate the damage program. Here we investigate intrinsic versus extrinsic cell death pathway activation using caspase cleavage as a marker for activation of these pathways in a rat in vitro model of seizures. Hippocampal cells, chronically treated with kynurenic acid, had kynurenic acid withdrawn to induce seizure-like activity for 40 min. Subjecting rat hippocampal cultures to seizures increased cell death and apoptosis-like DNA fragmentation using TUNEL staining. Seizure-induced cell death was blocked by both MK801 (10 microM) and CNQX (40 microM), which suggests multiple glutamate receptors regulate seizure-induced cell death. Cleavage of the initiator caspases, caspase 8 and 12 were increased 4h following seizure, and cleavage of the quintessential executioner caspase, caspase 3 was increased 4h following seizure. In contrast, caspase 9 cleavage only increased 24h following seizure. Using an affinity labeling approach to trap activated caspases in situ, we show that caspase 8 is the apical caspase activated following seizures. Finally, we show that the caspase 8 inhibitor Ac-IETD-CHO was more effective at blocking seizure-induced cell death than the caspase 9 inhibitor Ac-LEHD-CHO. Taken together, our data suggests the extrinsic cell death pathway-associated caspase 8 is activated following seizures in vitro.

Seizure-like activity leads to the release of BAD from 14-3-3 protein and cell death in hippocampal neurons in vitro.

Seizure-induced neuronal death may involve engagement of the BCL-2 family of apoptosis-regulating proteins. In the present study we examined the activation of proapoptotic BAD in cultured hippocampal neurons following seizures induced by removal of chronic glutamatergic transmission blockade. Kynurenic acid withdrawal elicited an increase in seizure-like electrical activity, which was inhibited by blockers of AMPA (CNQX) and NMDA (MK801 and AP5) receptor function. However, only NMDA receptor antagonists inhibited calcium entry as assessed by fura-2, and cell death of hippocampal neurons. Seizures increased proteolysis of caspase-3 and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) of cells. Seizure-like activity induced dephosphorylation of BAD and the disruption of its constitutive interaction with 14-3-3 proteins. In turn, BAD dimerized with antiapoptotic BCL-Xl after seizures. However, the absence of neuroprotective effects of pathway intervention suggests that BAD may perform a reinforcement rather than instigator role in cell death following seizures in vitro.

Coulomb energy differences in t = 1 mirror rotational bands in (50)Fe and (50)Cr.

Gamma rays from the N = Z-2 nucleus (50)Fe have been observed, establishing the rotational ground state band up to the state J(pi) = 11+ at 6.994 MeV excitation energy. The experimental Coulomb energy differences, obtained by comparison with the isobaric analog states in its mirror (50)Cr, confirm the qualitative interpretation of the backbending patterns in terms of successive alignments of proton and neutron pairs. A quantitative agreement with experiment has been achieved by exact shell model calculations, incorporating the differences in radii along the yrast bands, and properly renormalizing the Coulomb matrix elements in the pf model space.

Observation of (46)Cr and testing the isobaric multiplet mass equation at high spin.

The ground state band in (46)Cr and the isospin T = 1 band in (46)V have been delineated up to Ipi = 10(+) (tentatively 12(+)). These observations complete the highest spin T = 1 isospin triplet known. Following the isobaric multiplet mass equation, a combination of level energies in (46)Cr, (46)Ti, and (46)V are taken to highlight the angular momentum dependence of the isovector and isotensor parts of the interaction. The results are compared with full- fp-space shell model calculations. The influence of the one-body and two-body contributions to the isovector energy difference are investigated.

Stress and nutritional quality of broilers.

Broiler chicks were reared in environmental chambers. All birds were started under ideal conditions, i.e., 30.6 C with 35% RH. Beginning at Day 36, half of the chicks were maintained at 24 C and 35% RH. The other half were subjected to a cyclic temperature-RH regime that approximated a typical August day in central Mississippi (heat treatment). Half of each of the described groups received implants of osmotic pumps that released adrenocorticotropin (ACTH) at 8 IU/kg BW/d for 7 d. The remaining birds received placebo pumps. The main effects of ACTH and heat treatments were similar. Both treatments caused reductions in BW, carcass weight (CW), carcass protein (CP), and muscle calorie (C) content. ACTH, but not heat, reduced carcass moisture (M). Carcass fat and ash, however, were not affected. Most changes were not reversed after 1 wk of recovery. Although visible signs of pale, soft, exudative muscle (PSE) were present, "white" areas of muscle were absent. The decreased meat yield and detrimental changes in meat quality suggest that stress, whether induced hormonally or by exposure to over-heating, caused losses that were as severe as those associated with PSE under field conditions.

Extent of ossification at the amputation plane is correlated with the decline of blastema formation and regeneration in Xenopus laevis hindlimbs.

Xenopus laevis larvae gradually lose the ability to regenerate lost hindlimb structures as they progress through metamorphosis. Previous studies have suggested that this loss of regenerative capacity occurs in a proximal-to-distal fashion. We assessed the quality of overall regeneration and early bud blastema formation in order to evaluate previous explanations for this loss of regenerative ability in Xenopus. We further examined the extent to which epidermis, basement membrane, dermis, cartilage, bone, periosteum, and accumulated mesenchyme within the blastema are involved in the decline of regenerative abilities during mid-metamorphic stages of development. Each tissue was scored based on its contributions to the regeneration blastema, in accordance with previously reported blastemal descriptions. Tadpoles amputated at the ankle and tarsal-metatarsal joints scored objectively higher within the overall regeneration and blastema quality rating systems. Both joint sites met more criteria associated with regeneration-capable blastemas than tadpoles amputated through the middle of the tarsus, especially at later stages of metamorphosis. The three amputation sites studied began to vary in their ability to regenerate skeletal elements and to generate productive blastemas during the same stages at which we initially observed ossification of the tarsus. These results suggest that the decline of Xenopus hindlimb regeneration does not occur in a strictly proximal-to-distal fashion but rather is dependent at later stages on the state of ossification of the structure through which amputation occurs. Our morphological and cellular observations reveal specific times and places during Xenopus hindlimb development at which further investigations into tissue-specific molecular events during early regeneration should be focused.

Physiological responses associated with sustained delivery of T, DHT, and AED in male rats.

The factors responsible for the marked gender difference in the risk of coronary heart disease and remain controversial. Several clinicians and basic scientists support the hypothesis that a protective effect of endogenous estrogen is the key, however epidemiological data failed to prove this trend. The role of endogenous androgens or sex steroid hormones on the development of atherosclerosis has received little attention over the years. The specific objectives of this study are: 1) to deliver testosterone (T), dihydrotestosterone (DHT), or androstenedione (AED) at sustained levels by tricalcium phosphate lysine (TCPL) ceramic delivery devices, and 2) to quantify major biochemical markers levels such as lactate dehydrogenase activity (LDH), total cholesterol, thiobarbituric reactive species associated with sustained delivery of androgens and 3) to evaluate the histopathological changes in vital and reproductive organs associated with excess androgens delivery in adult intact male rats. A total of sixteen male rats were randomly divided into four equal groups. Rats in group I served as intact controls, and animals in groups II-IV were implanted with a single TCPL delivery device contained T (40 mg), DHT (40 mg), or AED (40 mg), respectively. Animals in all groups were weighed and blood was drawn biweekly for cholesterol, LDH and TBAR analysis. At the end of ninety days post implantation, the animals were sacrificed and the organs removed, processed embedded, sectioned and screened for morphological changes. The results of this study suggest that: 1) sustained deliver of androgens caused a statistically significant increase (p < 0.05) in the prostate and the seminal vesicle weights, while the epididymis weights remained similar to control intact animals, 2) decreases in adrenal gland weight was detected in animals treated with androgens compared to control animals, 3) kidney weights increased in all androgen groups compared to control, 4) no differences were observed in heart, spleen, or body weights between the groups, 5) TBAR analysis, as well as LDH activity were not different between androgen treated animals and control animals, and 6) total cholesterol was significantly reduced in T and DHT treated groups compared with control and AED treated animals. The decrease in total cholesterol and reduction in adrenal gland weight may suggest impairment of cholesterol synthesis. In conclusion, this study provides information on the effects of sustained release of DHT, T and AED on the reproductive organs, vital organs, as well as physiological parameters such as TBARS (cellular damage) and total cholesterol.

Inhibition of nitric oxide synthesis potentiates hypertension during chronic glucose infusion in rats.

Endothelial dysfunction has been proposed to contribute to impaired blood flow control or hypertension in many conditions characterized by hyperinsulinemia or hyperglycemia. However, most studies have focused on whether endothelial dysfunction is present in the established phases of these various hypertensive states, and there is little known concerning the role of the endothelium in the initial stages. This study tested whether nitric oxide production, before endothelial dysfunction develops, plays an important role in counteracting the hypertensive response to chronic glucose infusion. Glucose was infused (18.6 mg/kg per minute IV) for 7 days in 8 normal rats (G) and in 9 rats with a long-term background intravenous infusion of N(G)-nitro-L-arginine methyl ester (L-NAME) at 10 microg/kg per minute (G+L). Mean arterial pressure (MAP), measured 24 hours per day, increased an average of approximately 11 mm Hg in the G rats. L-NAME treatment increased MAP an average of 28+/-2 mm Hg in the G+L rats, and glucose infusion raised MAP >30 mm Hg above that, averaging 155+/-8 mm Hg by day 6. In addition, heart rate increased from an average of 389+/-8 bpm to 441+/-16 bpm by day 6, whereas there was no significant change in the G rats. Glomerular filtration rate decreased significantly with L-NAME treatment and decreased in both groups by day 3 of glucose infusion, reaching lower levels in the G+L rats. These results show that NO is required to minimize the increase in MAP during glucose infusion and suggest that renal and neural mechanisms may be important in mediating that effect.

Tendinosis and tears of gluteus medius and minimus muscles as a cause of hip pain: MR imaging findings.

OBJECTIVE: This study was conducted to determine the prevalence of tendinosis and tears of gluteus medius and minimus muscles in patients presenting with buttock, lateral hip, or groin pain; describe the MR imaging findings; and discuss their probable relationship to the greater trochanteric pain syndrome. SUBJECTS AND METHODS: Two hundred fifty MR imaging examinations of the hip were performed for the evaluation of buttock, lateral hip, or groin pain. The findings were reviewed for changes in the morphology or signal intensity of gluteus medius and minimus muscles and tendons and for any peritendinous abnormality including distention of regional bursae. RESULTS: Thirty-five studies met our criterion of showing either tendinosis or tears of gluteus medius and minimus muscles as the primary positive finding. Eight patients had complete retracted tears of the gluteus medius, and 14 patients had partial tears; in 13 patients, MR findings were consistent with tendinosis. The gluteus minimus muscle was also involved in 10 patients. MR imaging findings were the same as those described for tears and tendinosis of other regions of the body. Surgical proof of a tendon tear was obtained in six patients. CONCLUSION: Tendinopathy of the hip abductors and gluteus medius and minimus muscles was a common finding on MR imaging in our patients with buttock, lateral hip, or groin pain. Tendinopathy is probably a frequent cause of the greater trochanteric pain syndrome, a common regional pain syndrome that can mimic other important conditions causing hip pain including avascular necrosis and stress fracture. Moreover, it is likely that trochanteric bursitis is associated with tendinopathy.

Inhibition of calcium ATPase by phencyclidine in rat brain.

Phencyclidine (PCP) is a potent psychotomimetic drug of abuse and has profound effect on the functioning of the central nervous system (CNS). Many of the CNS functions are known to be mediated by calcium (Ca2+). In the present study we have investigated the effects of PCP on Ca2+ ATPase activity in rat brain both in vitro and in vivo. For in vitro studies, synaptic membrane fractions prepared from normal rat brain were incubated with PCP at different concentrations (25-100 microM) before the addition of substrate. For in vivo studies, rats were treated with a single moderate dose of PCP (10 mg/kg, i.p.) and animals were sacrificed at 1,2, 6 and 12 h after treatment. Ca2+ ATPase activity in synaptic membrane fractions was assayed by estimation of inorganic phosphate. PCP inhibited the Ca2+ ATPase in vitro in a concentration dependent manner with significant effect at 50 and 100 microM. A significant time-dependent reduction of the Ca2+ ATPase activity was evident in vivo. As early as 2 h after the treatment of rats with PCP the ATPase activity was significantly reduced. The reduction of Ca2+ ATPase observed even at 12 h after treatment suggesting a prolonged presence of the drug in the brain tissue. Further, kinetic studies in vitro indicated PCP to be a competitive inhibitor of Ca2+ ATPase with respect to the substrate, ATP. The present findings indicate that PCP inhibits synaptic membrane Ca2+ ATPase thus altering cellular Ca2+ homeostasis in CNS which may partially explain the pharmacological effects of the drug and/or its neurotoxicity.

Presurgical evaluation of the motor hand area with functional MR imaging in patients with tumors and dysplastic lesions.

PURPOSE: To test an optimized functional magnetic resonance (MR) imaging procedure to depict the motor hand representation area (HRA) in patients with epilepsy lesions near the central sulcus. MATERIALS AND METHODS: Fast low-angle shot MR imaging was performed with an oblique single-section imaging technique in eight control subjects (10 hemispheres) and six patients (12 hemispheres). Three series of five activation images (obtained while subjects performed repetitive finger-to-thumb opposition movements) and five rest images were acquired. Each hemisphere was studied in three adjacent sections. Difference maps (obtained with simple subtraction between activation and rest images) were compared with t-test maps. RESULTS: In control subjects, the HRA was visible in 27 of 30 sections. Qualitatively, activation was seen better on t-test maps in 14 and on difference maps in four of these sections. In all patients, motor activation could be seen in the hemisphere that contained the lesion. This activation was considered normal in four patients. In two patients, the HRA was deformed. Functional MR imaging activation in the motor area was confirmed with Penfield stimulation in five patients. CONCLUSION: Functional MR imaging findings in the preoperative assessment of dysplastic lesions around the central sulcus are the same as for tumors. t-test maps are superior to difference maps in the treatment of motor functional MR imaging data.

Phencyclidine block of Ca2+ ATPase in rat heart sarcoplasmic reticulum.

Phencyclidine hydrochloride (PCP) also known as Angel Dust is a very potent psychotomimetic drug of abuse. Besides its central nervous system (CNS) effects PCP produces a number of adverse effects in a variety of tissues including the cardiovascular system. Since PCP is known to alter the cellular calcium homeostasis the present studies were initiated to determine the changes in cardiac Ca2+ ATPase activity in rats treated with PCP. For in vitro studies the cardiac sarcoplasmic reticulum (SR) fractions prepared from normal rats were incubated with 25, 50 and 100 microM PCP and the enzyme activities were estimated. Whereas, for in vivo studies the cardiac SR fractions prepared from rats treated with PCP (10 mg/kg body wt. single dose, intra-peritoneally (i.p.)) and sacrificed at different time intervals were used. PCP reduced the Ca2+ ATPase activity significantly both in vitro and in vivo. A 50% inhibition of the enzyme activity was obtained with 100 microM PCP in vitro. A significant reduction of SR Ca2+ ATPase was also evident as early as 1 h after treatment of rats with PCP. The reduction of Ca2+ ATPase activity in SR was irreversible even at 12 h after treatment. The in vitro kinetic studies revealed that PCP was found to be a competitive inhibitor of Ca2+ ATPase with respect to the substrate, ATP, and non-competitive with respect to Ca2+ activation. These results indicate that PCP alters the myocardial Ca2+ homeostasis by inhibiting the Ca2+ ATPase in cardiac SR in rats. Inhibition of SR Ca2+ ATPase may result in the impairment of contraction and relaxation coupling processes in the myocardium.

Endophthalmitis cluster from contaminated donor corneas following penetrating keratoplasty.

OBJECTIVE: To attempt to identify common events or factors in four cases of endophthalmitis that developed after penetrating keratoplasty performed within a 1-week interval. DESIGN: Case series. SETTING: Tertiary care eye hospital in Riyadh, Saudi Arabia. PATIENTS: Four patients in whom endophthalmitis developed after penetrating keratoplasty performed in May 1993. OUTCOME MEASURES: Source of donor tissue, transportation of corneas, handling of corneas at the eye hospital, and causative organism and sensitivity profile. RESULTS: The donor tissue in all four cases originated from the same eye bank. Organisms were cultured from 10 of the 11 donor rims from eye bank A tissue used during the week in question. The causative organisms were Enterococcus faecalis in three patients and Torulopsis glabrata in one patient. In each case the same organism was cultured from the recipient eye and the corresponding donor rim. Two of the four patients had a favourable outcome. CONCLUSIONS: Donor rim culture is essential if the cause of endophthalmitis after penetrating keratoplasty is to be determined. Close communication between eye bank personnel, the microbiology laboratory and the operating surgeon is important as it may influence early detection, choice of treatment and outcome of endophthalmitis after penetrating keratoplasty. Epidemiologic studies from both the source eye bank and the recipient facility are required to fully investigate the cause of a cluster of endophthalmitis cases from contaminated donor tissue following penetrating keratoplasty.

Recurrence of climatic droplet keratopathy. Two case reports.

Climatic droplet keratopathy (CDK) is characterized by a band-shaped pattern of subepithelial opacities and golden-yellow spherules. Recurrence of this disease in corneal grafts has not been reported. We report two cases that developed recurrence of this disease in corneal grafts done for CDK, 3 1/2 years following lamellar penetrating keratoplasty and 6 years following penetrating keratoplasty. This illustrates the possibility of this degenerative disease to recur in a few years if aetiological factors are persistently present.