Brachytherapy for high grade prostate cancer induces distinct changes in circulating CD4 and CD8 T cells - Implications for systemic control.

This exploratory study is a follow up to our previous investigation of immune response in the circulation of high-grade Gleason 9 prostate cancer patients treated with EBRT + BT compared to EBRT alone. Notably, EBRT + BT demonstrates the potential to elicit an effect on CD4/CD8 ratio which may have attributed to improved clinical response to therapy. Our findings show promise for leveraging circulating immune cells as predictive biomarkers for radiotherapy response.

Universal structure of dark matter haloes over a mass range of 20 orders of magnitude.

Cosmological models in which dark matter consists of cold elementary particles predict that the dark halo population should extend to masses many orders of magnitude below those at which galaxies can form1-3. Here we report a cosmological simulation of the formation of present-day haloes over the full range of observed halo masses (20 orders of magnitude) when dark matter is assumed to be in the form of weakly interacting massive particles of mass approximately 100 gigaelectronvolts. The simulation has a full dynamic range of 30 orders of magnitude in mass and resolves the internal structure of hundreds of Earth-mass haloes in as much detail as it does for hundreds of rich galaxy clusters. We find that halo density profiles are universal over the entire mass range and are well described by simple two-parameter fitting formulae4,5. Halo mass and concentration are tightly related in a way that depends on cosmology and on the nature of the dark matter. For a fixed mass, the concentration is independent of the local environment for haloes less massive than those of typical galaxies. Haloes over the mass range of 10-3 to 1011 solar masses contribute about equally (per logarithmic interval) to the luminosity produced by dark matter annihilation, which we find to be smaller than all previous estimates by factors ranging up to one thousand3.

Publisher Correction: A dynamically cold disk galaxy in the early Universe.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A dynamically cold disk galaxy in the early Universe.

The extreme astrophysical processes and conditions that characterize the early Universe are expected to result in young galaxies that are dynamically different from those observed today1-5. This is because the strong effects associated with galaxy mergers and supernova explosions would lead to most young star-forming galaxies being dynamically hot, chaotic and strongly unstable1,2. Here we report the presence of a dynamically cold, but highly star-forming, rotating disk in a galaxy at redshift6 z = 4.2, when the Universe was just 1.4 billion years old. Galaxy SPT-S J041839-4751.9 is strongly gravitationally lensed by a foreground galaxy at z = 0.263, and it is a typical dusty starburst, with global star-forming7 and dust properties8 that are in agreement with current numerical simulations9 and observations10. Interferometric imaging at a spatial resolution of about 60 parsecs reveals a ratio of rotational to random motions of 9.7 ± 0.4, which is at least four times larger than that expected from any galaxy evolution model at this epoch1-5 but similar to the ratios of spiral galaxies in the local Universe11. We derive a rotation curve with the typical shape of nearby massive spiral galaxies, which demonstrates that at least some young galaxies are dynamically akin to those observed in the local Universe, and only weakly affected by extreme physical processes.

Laser Capture Microdissection of Feline Streptomyces spp Pyogranulomatous Dermatitis and Cellulitis.

Suspected Streptomyces spp infections were identified in 4 cats at UC Davis Veterinary Medical Teaching Hospital between 1982 and 2011. Three had ulcerated, dark red mycetomas involving the dermis, subcutis, and fascia with fistulous tracts and/or regional lymphadenopathy. One cat had pyogranulomatous mesenteric lymphadenitis. Granulomatous inflammation in all cats contained colonies of Gram-positive, non-acid-fast organisms. All 4 cats failed to respond to aggressive medical and surgical treatment and were euthanized. Laser capture microdissection (LCM) was used to selectively harvest DNA from the affected formalin-fixed, paraffin-embedded (FFPE) tissues. Cloned amplicons from LCM-derived tissue confirmed the presence of Streptomyces spp in the dermatitis cases. Amplicons from the remaining cat with peritoneal involvement aligned with the 16S ribosomal RNA gene for Actinomycetales. Usually considered a contaminant, Streptomyces spp can be associated with refractory pyogranulomatous dermatitis and cellulitis in cats with outdoor access. LCM is useful in the diagnosis of bacterial diseases where contamination may be an issue.

Lack of detectable equine herpesviruses 1 and 2 in paraffin-embedded specimens of equine sarcoidosis.

BACKGROUND: Equine sarcoidosis is a rare, multisystemic, noncaseating, granulomatous and lymphoplasmacytic disease of unknown etiology. A recent report described a horse with granulomatous skin disease displaying histologic, electron microscopic, and polymerase chain reaction (PCR) findings consistent with equine herpesvirus 2 (EHV-2). OBJECTIVE: To investigate the presence of EHV-2 and equine herpesvirus 1 (EHV-1) in 8 horses with sarcoidosis. ANIMALS: Eight horses with sarcoidosis, reported previously. METHODS: Retrospective study. PCR assays of the tissues were performed to detect DNA associated with EHV-1 and EHV-2. For both herpesviruses the target was their respective glycoprotein B gene. Positive controls consisted of DNA from viral cultures of culturettes from naturally occurring respiratory infections of EHV-1 and EHV-2. RESULTS: The PCR analyses for both equine herpesviruses' DNA were negative in all 8 horses. CONCLUSION: The failure to detect DNA from EHV-1 and EHV-2 in paraffin-embedded skin of these 8 horses does not discount EHV-1 or EHV-2 as causing some cases of ES, but lends support to the presumably multifactorial etiologic nature of the disease.

Prospects for detecting supersymmetric dark matter in the Galactic halo.

Dark matter is the dominant form of matter in the Universe, but its nature is unknown. It is plausibly an elementary particle, perhaps the lightest supersymmetric partner of known particle species. In this case, annihilation of dark matter in the halo of the Milky Way should produce gamma-rays at a level that may soon be observable. Previous work has argued that the annihilation signal will be dominated by emission from very small clumps (perhaps smaller even than the Earth), which would be most easily detected where they cluster together in the dark matter haloes of dwarf satellite galaxies. Here we report that such small-scale structure will, in fact, have a negligible impact on dark matter detectability. Rather, the dominant and probably most easily detectable signal will be produced by diffuse dark matter in the main halo of the Milky Way. If the main halo is strongly detected, then small dark matter clumps should also be visible, but may well contain no stars, thereby confirming a key prediction of the cold dark matter model.

Malassezia species isolated from the intermammary and preputial fossa areas of horses.

BACKGROUND: Malassezia-type yeasts previously have been observed on cytologic examination of the intermammary region of mares that presented with tail-head pruritus; topical antiyeast treatment resolved the pruritus. Further, Malassezia dermatitis has been observed in horses in intertriginous areas such as the udder and prepuce; the species of yeast was not confirmed. It is not known whether healthy mares or male horses can be carriers of this yeast in these body areas. HYPOTHESIS: Malassezia spp. are present in the intermammary region in healthy mares and the preputial fossa in healthy geldings. ANIMALS: Eleven healthy horses (5 mares and 6 geldings). METHODS: Samples of surface material were taken digitally from the intermammary area of 5 mares and the preputial fossa region of 6 geldings. The samples were examined cytologically and were cultured on modified Sabouraud's dextrose agar. The DNA from yeast colonies grown on the agar was extracted, and samples were assayed using fungal generic polymerase chain reaction (PCR) analysis. Amplicons with positive PCR results were sequenced and compared with sequences in the BLAST database search program. RESULTS: Of 44 attempts at culture, 5 yielded a species identified as Malassezia equi, and 2 yielded M slooffiae. In contrast, of 44 cytologic examinations, yeasts with the morphology of Malassezia spp. were seen in 40 samples. CONCLUSIONS AND CLINICAL IMPORTANCE: Due to its presence in healthy horses, finding of Malassezia-type yeast on cytologic examination may not incriminate it as a pathogen. Despite difficulty in culturing, cytologic examination was an effective tool to rapidly demonstrate the organism.

WITHDRAWN: Goat serum product "Aimspro" restores conduction in demyelinated human optic nerve fibres.

Ahead of Print article withdrawn by publisher.

Detection of circulating autoantibodies using living keratinocyte staining on MCA-B1 method in dogs with pemphigus foliaceus.

In this study, we compared the sensitivity and specificity of three immunofluorescence techniques used to detect circulating autoantibodies in dogs with pemphigus foliaceus (PF); living keratinocyte staining on a canine keratinocyte cell line, MCA-B1, indirect immunofluorescence (IIF) on canine lip and IIF on bovine esophagus. Sera from canine PF cases were positive in four out of 27 dogs (14.8%) using living keratinocyte staining on MCA-B1 cells method, and five (18.5%) and eight sera (29.6%) using IIF on canine lip and bovine esophagus methods, respectively. By contrast, none of the 31 sera from dogs with non-pemphigus dermatoses reacted with MCA-B1 cells, whereas two (6.5%) as well as five sera (16.1%) obtained from those dogs showed positive reactivity with IIF on canine lip and bovine esophagus, respectively. Our results suggest that, although it exhibits the least sensitivity, the positive reactivity obtained by living keratinocyte staining on MCA-B1 cells can support the diagnosis of canine PF.

Zinc-responsive dermatosis in dogs: 41 cases and literature review.

Forty-one cases of zinc-responsive dermatosis in the dog are described. The Siberian husky was the predominant breed affected. Periocular crusts were the most common clinical sign and parakeratosis was noted in the skin biopsy specimens of all dogs. Treatment with oral zinc ameliorated the clinical signs in most dogs, but cases necessitating other treatments such as parenteral zinc or retinoids are reported. The authors recommend a starting dose of 2-3 mg kg-1 elemental zinc per day in the treatment of this disorder.

Clinicopathologic findings, sensitivity to house dust mites and efficacy of milbemycin oxime treatment of dogs with Cheyletiella sp. infestation.

Twenty-three dogs with positive skin scrapings for Cheyletiella sp. were treated with milbemycin oxime using a protocol approximating 2 mg kg-1 orally once weekly for three weeks. Nineteen of these dogs belonged to a household of 41 dogs and two dogs were in households with one other dog. All in-contact dogs were treated. Pre-treatment intradermal skin tests showed positive reactions to D. farinae in 13 dogs and to D. pteronyssinus in 12 dogs; these became negative post-treatment in four and seven dogs, respectively. All dogs showed a dramatic reduction in clinical signs one week after the third treatment. Eighteen dogs no longer had mites on skin scrapings, three had dead mites and two had deformed eggs. Recurrence of clinical signs necessitated two additional courses of the protocol in the multiple dog household and for a dog receiving immunosuppressive treatment for pemphigus foliaceus. Possible adverse reactions to the milbemycin (vomiting, lethargy) were noted once in two dogs.

Thiopurine methyltransferase in red blood cells of dogs, cats, and horses.

Our objective was to determine if thiopurine methyltransferase (TPMT), the enzyme important in the metabolism of azathioprine in human beings, is detectable in red blood cell lysates (RBCL) of healthy dogs, cats, and horses. Values for TPMT activity were determined from blood collected from 20 healthy dogs, cats, and horses. The TPMT activity in each animal's RBCL was determined using a radioenzymatic end point involving TPMT-facilitated metabolism of 6-mercaptopurine to 6-methylmercaptopurine (6-MMP). One unit of TPMT activity represents the formation of 1 nmol of 6-MMP per milliliter of packed red blood cells per hour of incubation at 37 degrees C. TPMT activity in RBCL was detectable in all species, with mean RBC values +/- standard deviation of 17.9 +/- 3.79 U/mL in dogs; 2.76 +/- 0.70 U/mL in cats; and 2.185 +/- 0.36 U/mL in horses. Values for TPMT in the 3 species were significantly (P < .05) different from one another. TPMT values for dogs were significantly higher than the other species, and TPMT values for cats were significantly higher than those for horses. We conclude that RBCL TPMT values are measurable in dogs. cats, and horses and that dogs have higher values than cats or horses. These findings are consistent with the lower tolerance for azathioprine in cats as compared with dogs. It remains to be determined whether RBCL TPMT values in these species correlate with TPMT activity in the liver, where most of the metabolization of azathioprine is believed to occur.

Intonational disambiguation in sentence production and comprehension.

Speakers' prosodic marking of syntactic constituency is often measured in sentence reading tasks that lack realistic situational constraints on speaking. Results from such studies can be criticized because the pragmatic goals of readers differ dramatically from those of speakers in typical conversation. On the other hand, recordings of unscripted speech do not readily yield the carefully controlled contrasts required for many research purposes. Our research employs a cooperative game task, in which two speakers use utterances from a predetermined set to negotiate moves around gameboards. Results from a set of early versus late closure ambiguities suggest that speakers signal this syntactic difference with prosody even when the utterance context fully disambiguates the structure. Phonetic and phonological analyses show reliable prosodic disambiguation in speakers' productions; results of a comprehension task indicate that listeners can successfully use prosodic cues to categorize syntactically ambiguous fragments as portions of early or late closure utterances.

Deciphering "integrated Chinese and Western medicine" in the rural Lijiang basin: state policy and local practice(s) in socialist China.

Based on ethnographic research during an eighteen-month period in 1989-90, this article explores the rural practice of "integrated Chinese and Western medicine" (integrated medicine) in southwest China's Lijiang basin. Integrated medicine is a consciously formulated hybrid medical practice that was introduced by Chairman Mao during the Cultural Revolution as the cornerstone of national health policy. It was originally envisioned as the epistemological handmaiden of the "cooperative health care" system (of "barefoot doctor" fame). The relationship between the respective People's Republic of China (PRC) practices of "Chinese medicine" and "Western medicine" embedded in integrated medicine is explored here on two levels. Integrated medicine is analyzed both as a state policy and as an everyday practice engaged in by village practitioners and lay villagers alike. During the Maoist period, integrated medicine in the rural Lijiang basin was particularly receptive to local interpretation and experimentation by "the masses." This local license in interpreting state policy represented a point of contrast between integrated medicine and other state-sanctioned medical practices. During the ensuing first decade of the post-Mao period, a popular cultural influence on integrated medicine persisted. Integrated medicine is thus examined here both in terms of how state/urban/elite agencies have enacted processes of "syncretism from above" as well as how local/rural/peasant agencies have enacted processes of "syncretism from below" in shaping it as a therapeutic practice. Rural Lijiang basin explanatory models reveal a pattern whereby afflictions are classified according to either "medicine of systematic correspondence" criteria or "stigmatized affliction" criteria. Both types of criteria reflect distinctive interpretations and appropriations of theories rooted in Chinese therapeutic practices and "Western medicine," respectively. The rural basin practice of integrated medicine thus reflects a local appropriation and mediation of state policy, and provides some insight into the nature of a "circularity" that operates between local (or popular) knowledge and state policy in the PRC.

Stability study on specimens mailed to a state laboratory and tested with the Gen-Probe PACE 2 assay for chlamydia.

BACKGROUND: Although specimen collection is acknowledged to be a critical factor in the testing of chlamydia, rarely do studies examine the effects of specimen transport on laboratory results. GOAL: To compare the results on specimens shipped in a controlled environment with duplicate specimens exposed to environmental conditions such as heat or extended time in transit. STUDY DESIGN: Duplicate specimens were collected from 1,017 women tested at South Carolina public health clinics. One specimen from each woman was shipped by courier and the other by U.S. mail. The results, swab collected first, method of transport, and temperature during shipment were compared for each set of specimens. Specimens were tested with the Gen-Probe PACE 2 test. RESULTS AND CONCLUSIONS: Mailed specimens were exposed to longer transport times and elevated temperatures; despite this, 99% of the results using courier specimens agreed with the mailed specimen results. Eighty-eight women tested positive and 891 women tested negative for chlamydia on both specimens. When the 11 specimens with discrepant results were retested by polymerase chain reaction, 10 were positive for chlamydia, with 9 concurring with the mailed specimen results. Results of specimens in this study were not adversely affected by heat and extended transit times when transported by U.S. Mail.

Sebaceous adenitis in dogs and results of treatment with isotretinoin and etretinate: 30 cases (1990-1994).

Medical records of 30 dogs with histologically confirmed sebaceous adenitis that were treated with isotretinoin or etretinate were reviewed. Akitas and Standard Poodles were overrepresented, compared with the general hospital population. Thirteen dogs had concurrent pyoderma. The retinoids were administered for a minimum of 2 months. Dosage for the 13 dogs treated with isotretinoin only ranged from 0.8 to 3.5 mg/kg of body weight/d (mean, 1.4 mg/kg/d). Dosage for the 10 dogs treated with etretinate only ranged from 0.7 to 1.8 mg/kg/d (mean, 1.1 mg/kg/d). Two dogs were first given isotretinoin (mean dosage, 1.5 mg/kg/d) and, when they did not respond, were subsequently given etretinate (mean dosage, 0.85 mg/kg/d). Five dogs were first given etretinate (mean dosage, 1 mg/kg/d) and, when they did not respond, were subsequently given isotretinoin (mean dosage, 1.6 mg/kg/d). For the 20 dogs treated with isotretinoin, 1 was lost to follow-up; 9 of the remaining 19 had a successful outcome (> 50% reduction in severity of scaling and extent of alopecia, compared with pretreatment appearance). For the 17 dogs treated with etretinate, 9 had a successful outcome. Outcome could not be predicted on the basis of clinical signs or histologic findings, and a prognosis could not be determined on the basis of whether sebaceous glands were evident histologically.

Goal setting and control orientation of pregnant / parenting female adolescents in the GRADS program.

PIP: The Graduation, Reality, and Dual-role Skills (GRADS) home economics program helps at-risk pregnant/parenting teens graduate from high school, set life goals, and feel empowered. It was initiated in Ohio in 1980 and started in New Mexico in 1989. The authors investigated whether female GRADS students differed from nonpregnant/nonparenting female teens in terms of the types of goals they perceive to be most important, the tendency to set goals, and control orientation. Comparisons were made between 37 female GRADS students in the program for one year or more, 46 female GRADS students new to the program, and 68 nonpregnant/nonparenting female students from an English class. The data were collected during Fall 1992 from eight sites in New Mexico. Analysis of the data found the existence of significant differences regarding participants' most important goals, but no significant differences in goal orientation or locus of control among the three groups. GRADS students were highly concerned about interpersonal relationships, while the nonpregnant/nonparenting students were highly interested in personal concerns. Pregnant and/or parenting teens were more like their nonpregnant/nonparenting peers than different, with the differences in goals seeming to reflect different priorities.^ieng

Diseases of the nasal planum.

The most common clinical sign for owners to seek veterinary care in reference to the nasal planum is depigmentation in dogs and ulceration in cats. Proliferative (nodular) diseases are less common in dogs than in cats, because cats are more prone to develop squamous cell carcinoma of the nasal planum. Because a wide variety of diseases may present with similar clinical signs, the most helpful diagnostic test (after a thorough history and physical examination) is a skin biopsy. Discoid lupus erythematosus is the most common disease affecting the nasal planum of dogs in the author's practice.