Despite vaccination programs and antivirals, influenza remains a prominent cause of morbidity and mortality. The Xpert Xpress Flu/respiratory syncytial virus (RSV) test is a leading influenza ...point‐of‐care test, but its evaluation has been limited to nasopharyngeal samples. In addition, the clinical impacts of Xpress Flu/RSV have not yet been quantified. We evaluated the performance of Xpress Flu/RSV at three locations in a UK Hospital Trust against an existing laboratory assay. Multiple upper respiratory tract sample types were included. In addition, we calculated time saved by Xpert, and the associations between Xpert use and rates of early patient isolation and antiviral prescription as recorded at the time of the laboratory result being telephoned out. A total of 642 patients were included in the diagnostic performance analysis. There were 177 laboratory‐confirmed cases of influenza A, 7 influenza B and 86 RSV. For influenza A, sensitivity and specificity were 96.6% (95% confidence interval CI: 92.8%–98.8%) and 98.1% (CI: 96.4%–99.1%), respectively. This was sustained across all locations and sample types. The negative predictive value was 98.7% (CI: 97.2%–99.4%). The median amount of time saved was 27.1 h. Xpert use was associated with sixfold higher rates of isolation and threefold higher rates of antiviral prescribing by the time the laboratory result was available. Sensitivity for RSV was lower at 86.0% (95% CI: 76.9%–92.6%). Xpert Xpress Flu/RSV reliably detects influenza A infection and has significant clinical impacts. Cartridge optimization is required to enable accurate multiplexing, including from a range of sample types.
Impaired aqueous humor flow from the eye may lead to elevated intraocular pressure and glaucoma. Drainage of aqueous fluid from the eye occurs through established routes that include conventional ...outflow via the trabecular meshwork, and an unconventional or uveoscleral outflow pathway involving the ciliary body. Based on the assumption that the eye lacks a lymphatic circulation, the possible role of lymphatics in the less well defined uveoscleral pathway has been largely ignored. Advances in lymphatic research have identified specific lymphatic markers such as podoplanin, a transmembrane mucin-type glycoprotein, and lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1). Lymphatic channels were identified in the human ciliary body using immunofluorescence with D2-40 antibody for podoplanin, and LYVE-1 antibody. In keeping with the criteria for lymphatic vessels in conjunctiva used as positive control, D2-40 and LYVE-1-positive lymphatic channels in the ciliary body had a distinct lumen, were negative for blood vessel endothelial cell marker CD34, and were surrounded by either discontinuous or no collagen IV-positive basement membrane. Cryo-immunogold electron microscopy confirmed the presence D2-40-immunoreactivity in lymphatic endothelium in the human ciliary body. Fluorescent nanospheres injected into the anterior chamber of the sheep eye were detected in LYVE-1-positive channels of the ciliary body 15, 30, and 45 min following injection. Four hours following intracameral injection, Iodine-125 radio-labeled human serum albumin injected into the sheep eye (n = 5) was drained preferentially into cervical, retropharyngeal, submandibular and preauricular lymph nodes in the head and neck region compared to reference popliteal lymph nodes (P < 0.05). These findings collectively indicate the presence of distinct lymphatic channels in the human ciliary body, and that fluid and solutes flow at least partially through this system. The discovery of a uveolymphatic pathway in the eye is novel and highly relevant to studies of glaucoma and other eye diseases.
To examine relationships between pituitary tumors and lesion size, invasiveness, resectability, deoxyribonucleic acid ploidy, cell cycle profile, mitotic activity, and immunoreactivity for MIB-1, ...proliferating cell nuclear antigen (PCNA), p27Kip1, and p53.
One hundred fifty-three adenomas of most pathological subtypes, including 20 medically treated and prolactin and growth hormone-containing tumors, as well as 10 premetastatic tumors and 13 pituitary carcinomas, were studied.
Significant (P < 0.05) differences were noted between functional versus nonfunctional adenomas (percent aneuploidy, percent S phase, p27Kip1 labeling indices LI, male sex, tumor size, and frequency of visual disturbance); Cushing's versus silent adrenocorticotropin adenomas (percent hypertetraploidy, p53 LI, tumor size, visual disturbance, and resectability); untreated versus medically treated prolactin cell adenomas (MIB-1 LI, p53 LI, and resectability); untreated versus medically treated growth hormone-containing adenomas (percent diploidy, percent S phase, MIB-1 LI, p53 LI, and p27 LI); untreated prolactin cell adenomas versus premetastatic tumors (percent hypertetraploidy, PCNA LI, p53 LI, invasiveness, and resectability); untreated growth hormone-containing adenomas versus premetastatic tumors (percent diploidy, percent S phase, PCNA LI, p53 LI, invasiveness, and resectability); Cushing's adenomas versus premetastatic tumors (percent diploidy, percent hypertetraploidy, percent S phase, MIB-1 LI, p53 LI, tumor size, invasiveness, visual disturbance, and resectability); Nelson's adenomas versus premetastatic tumors (p53 LI, tumor size, invasiveness, and resectability); silent adenomas as a whole versus nonfunctional adenomas (percent nondiploid, percent S phase, invasiveness, and respectability); silent adrenocorticotropin adenomas I and II versus silent adenoma Subtype III (invasiveness); silent adrenocorticotropin adenoma Subtypes I and II versus premetastatic tumors (MIB-1 LI and invasiveness); silent adenoma Subtype III versus premetastatic tumors (PCNA and p53 LI); and premetastatic tumors versus metastatic pituitary carcinomas (MIB-1 LI).
Only trends toward differences were noted between Cushing's versus Nelson's adenomas and between prolactinomas of reproductive female patients versus those of menopausal female patients and male patients. Too few "atypical adenomas" were encountered to permit their comparison with premetastatic tumors, but our results suggest that most pituitary carcinomas arise by malignant transformation from adenomas.
Permanent ectoparasites live in stable environments; thus, their population dynamics are mostly adapted to changes in the host life cycle. We aimed to investigate how static and dynamic traits of ...red-footed falcons interplay with the dynamics of their louse subpopulations during breeding and how they affect the colonisation of new hosts by lice. We sampled red-footed falcon (
Falco vespertinus
) nestlings (two breeding seasons) and adults (one breeding season) in southern Hungary. The mean abundance of
Colpocephalum subzerafae
and
Degeeriella rufa
lice on the nestlings was modelled with generalized linear mixed models using clutch size and host sex in interaction with wing length. For adults, we used wing length and the number of days after laying the first egg, both in interaction with sex.
D. rufa
abundances increased with the nestlings’ wing length. In one year, this trend was steeper on females. In adult birds, both louse species exhibited higher abundances on females at the beginning, but it decreased subsequently through the breeding season. Contrarily, abundances were constantly low on adult males. Apparently,
D. rufa
postpones transmission until nestlings develop juvenile plumage and choose the more feathered individual among siblings. The sexual difference in the observed abundance could either be caused by the different plumage, or by the females’ preference for less parasitized males. Moreover, females likely have more time to preen during the incubation period, lowering their louse burdens. Thus, sex-biased infestation levels likely arise due to parasite preferences in the nestlings and host behavioural processes in the adult falcons.
Precision agricultural (PrA) technology relies on the utilization of special equipment to access real time observations on plant health status, chlorophyll, nitrogen content, and soil moisture ...content. In this research new PrA technology (i.e., SPAD (Soil Plant Analysis Development), and UAV-based NDVI (Unmanned Aerial Vehicle-based Normalized Difference Vegetation Index) were used to monitor maize yield based on different filed trials in eastern part of Hungary. Our study aimed to examine the utilization of PrA technology specifically SPAD and UAV-based NDVI measurements for monitoring maize GY under irrigated and rainfed experimental setups in Hungary with varied nitrogen treatment for the year 2022. The results showed that the SPAD increased in all treatments (14.7 %; p < 0.05) from V6–V8 in the rainfed treatments, decreased significantly (p < 0.05) by 13.9 % (R1) and 30.6 % (R3). However, implementation of irrigation significantly increased the SPAD values in majority of treatments. Also, results reveal that, under irrigated and rainfed conditions the highest UAV-based NDVI value (0.703, 0.642) was obtained in V12 (A120 treatment) and highest NDVI value (0.728, 0.662) was obtained in Vn (A120 treatment). Remarekedly, irrigation led to significant differences (p < 0.05) of UAV-based NDVI values compared with none irrigated. On the other hand, implementation of 120 kg N ha−1 before sowing led to highest GY, especially under irrigated conditions (8.649 Mg ha−1). The overall mean GY under rainfed treatment was 6.256 Mg ha−1, while under irrigated treatment it increased by 37.2 % and reached 8.581 Mg ha−1 (p < 0.05). In conclusion, PrA technology will support farmers in making informed decisions regarding fertilization strategies and timing, which will in turn maximize yield and minimize risk.
Display omitted
•SPAD and UAV- based NDVI proved to be efficient for monitoring maize yield.•R3 maize growth stage had the highest correlation of UAV-NDVI with N-fertilization and GY.•120 kg N ha−1 before sowing is recommended to achieve highest UAV-NDVI and GY, under irrigated conditions.
MGMT promoter hypermethylation of aggressive pituitary adenomas and pituitary carcinomas and low protein expression are implicated in improved response to treatment with temozolomide (TMZ). The aim ...of the present study was to investigate MGMT promoter methylation and immunoexpression in an aggressive subset of pituitary adenomas and carcinomas. Our material consisted of 12 silent subtype 3 (SS3) adenomas, 10 primary carcinomas, and 4 disseminated metastases. Two different tissue samples of 7 of the 12 SS3 adenomas and all carcinomas were analyzed for MGMT promoter methylation and immunohistochemical expression of MGMT. Immunoexpression was assessed semi-quantitatively as a percentage of immunoreactive nuclei. Overall 33% of carcinomas exhibited homogenous MGMT methylation in tumor and metastatic specimens. Low immunohistochemical MGMT expression was noted in 50% of carcinomas. Overall, 42% of the SS3 adenomas exhibited MGMT promoter methylation. MGMT immunostaining was predominantly negative (92%), with homogenous immunostaining results across different samples. Whereas all the methylated SS3 adenomas had low MGMT immunoreactivity, five unmethylated adenomas exhibited absent/low MGMT expression. There was no relationship between methylation status and MGMT immunoexpression was not apparent. MGMT methylation and low immunohistochemical expression seen in a subset of carcinomas and SS3 adenomas, suggesting that a subset of tumors may respond to treatment with TMZ. Heterogeneous MGMT methylation status in SS3 adenomas and the lack of concordance between methylation and immunohistochemical expression of MGMT suggest complex regulatory mechanisms, highlighting the need for improved methods in the research on a correlation between MGMT changes and response to TMZ.
This study aimed to address the need for adaptation of the current model of chronic obstructive pulmonary disease (COPD) care in Switzerland, particularly in regard to acute exacerbations, and how ...far an integrated approach involving advanced nursing practice can meet those needs.
A state analysis guided by the PEPPA framework was initiated by the Pulmonology Clinic of University Hospital Zürich. Literature describing the current provision of COPD care regarding exacerbations in Switzerland and international qualitative studies describing the patient perspective were systematically searched and summarised. The health providers' perspective was investigated in three focus-group interviews.
A lack of systematic and state-of-the-art support for patient self-management in Switzerland was described in literature and confirmed by the health providers interviewed. While care was assessed as being comprehensive and of good quality in each individual sector, such as inpatient, outpatient, rehabilitation and home settings, it was identified as being highly fragmented across sectors. The interview participants described day-to-day examples in which a lack of support in COPD self-management and fragmentation of care negatively affected the patients' disease management.
The necessity of coordinating the transition between healthcare sectors and self-management support and that these organisational boundaries should be addressed by a multi-professional team were identified. Initial evaluation indicates that advanced practice nurses potentially have the skill set to coordinate the team and address patients' self-management needs in complex patient situations. However, the legal foundation and a reimbursement system to ensure long-term implementation is not yet available.
Intrinsic and extrinsic stimuli result in profound pituitary growth changes ranging from hypoplasia to hyperplasia. Pituitary tumor transforming gene (PTTG) abundance correlates with pituitary ...trophic status. Mice with Pttg inactivation exhibit pituitary hypoplasia, whereas targeted pituitary PTTG overexpression driven by α-subunit glycoprotein (αGSU) promoter results in focal pituitary hyperplasia. To test the impact of pituitary hyperplasia on tumor development, we crossbred αGSU.PTTG with Rb+/− mice, which develop pituitary tumors with high penetrance. Pituitary glands of resulting bitransgenic αGSU.PTTGxRb+/− mice were compared with monotransgenic αGSU.PTTG, Rb+/−, and wild-type mice. Confocal microscopy showed that PTTG-overexpressing cells have enlarged nuclei and marked redistribution of chromatin, and electron microscopy of αGSU.PTTG pituitaries showed enlarged gonadotrophs with prominent Golgi complexes and numerous secretory granules. These morphological findings were even more remarkable in αGSU.PTTGxRb+/− pituitaries. Mice from all four genotypes were sequentially imaged by magnetic resonance imaging to evaluate pituitary volume, and glands from αGSU.PTTGxRb+/− mice were the largest as early as 2 months of age (P = 0.0003). Cumulative incidence of pituitary tumors visualized by magnetic resonance imaging did not differ between Rb+/− and αGSU.PTTGxRb+/− mice. However, anterior lobe tumors determined after necropsy were 3.5 times more frequent in αGSU.PTTGxRb+/− than in Rb+/− mice (P = 0.0036), whereas the frequency of intermediate lobe tumors was similar. In summary, αGSU.PTTGxRb+/− pituitary glands exhibit enhanced cellular activity, increased volume, and higher prevalence of anterior pituitary tumors, indicating that changes in pituitary PTTG content directly relate to both pituitary trophic status and tumorigenic potential.
OBJECTIVES:We hypothesized that resveratrol administration would reverse sepsis-dependent downregulation of peroxisome proliferator activated receptor-γ coactivator 1α, preserve mitochondrial ...integrity, and rescue animals from sepsis-induced myocardial failure.
SETTING:Teaching hospital research laboratory.
INTERVENTIONS:Cecal ligation and puncture in mice was performed to induce sepsis. Mice that underwent cecal ligation and puncture were randomly assigned to receive resveratrol (30 mg/kg or 60 mg/kg) or vehicle 1 mL sodium chloride 0.9% subcutaneously in the scruff of the neck directly after surgery and at 16, 24, and 40 hrs, respectively.
MEASUREMENTS AND RESULTS:Forty-eight hrs after cecal ligation and puncture, cardiac performance was established using echocardiography. Mitochondrial integrity was evaluated with electron microscopy, and changes in gene expression were evaluated with microarray analysis. Survival at 48 hrs was just under 50% and comparable between groups. Myocardial contractile function significantly improved after resveratrol treatment. Resveratrol-treated mice developed focal areas of edema, whereas vehicle-treated mice developed significant, diffuse myocardial edema. Electron microscopy revealed widespread swollen mitochondria with ruptured outer membranes, autophagosomes, and vacuolation of the internal compartment, which were significantly attenuated in resveratrol-treated animals. Resveratrol treatment significantly increased cardiac expression of peroxisome proliferator–activated receptor-γ coactivator 1a. Microarray analysis revealed that resveratrol treatment resulted in upregulation of the peroxisome proliferator–activated receptor-γ coactivator gene set containing genes known to be regulated by this transcriptional coactivator. Our data strongly suggest that administration of resveratrol modulates bioenergy metabolism, substrate utilization, oxidative stress, and detoxification pathways associated with both mitochondrial and cardiac pathological conditions, but does not alter mortality from sepsis.
CONCLUSIONS:The salutary effects of resveratrol on cecal ligation and puncture-induced myocardial dysfunction are associated with increased peroxisome proliferator–activated receptor-γ coactivator 1a abundance and function. Preservation of myocardial energy production capacity, prevention of secondary injury, mitigation of inflammation, and reversal of sepsis-induced myocardial remodeling are likely to underlie its beneficial effects. This however, does not result in improved survival.
To describe the case of a patient with an unusual plurihormonal pituitary adenoma with immunoreactivity for thyroid-stimulating hormone (TSH), growth hormone, follicle-stimulating hormone, prolactin, ...and α-subunit.
We report the clinical, laboratory, imaging, and pathology findings of a patient symptomatic from a plurihormonal pituitary adenoma and describe her outcome after surgical treatment.
A 60-year-old woman presented to the emergency department with headaches, blurry vision, fatigue, palpitations, sweaty hands, and weight loss. Her medical history was notable for hyperthyroidism, treated intermittently with methimazole. Magnetic resonance imaging disclosed a pituitary macroadenoma (2.3 by 2.2 by 2.0 cm), and preoperative blood studies revealed elevated levels of TSH at 6.11 mIU/L, free thyroxine at 3.6 ng/dL, and free triiodothyronine at 6.0 pg/mL. She underwent an uncomplicated transsphenoidal resection of the pituitary adenoma. Immunostaining of tumor tissue demonstrated positivity for not only TSH but also growth hormone, follicle-stimulating hormone, prolactin, and α-subunit. The Ki-67 index of the tumor was estimated at 2% to 5%, and DNA repair enzyme O6-methylguanine-DNA methyltransferase immunostaining was mostly negative. Electron microscopy showed the ultrastructural phenotype of a glycoprotein-producing adenoma. Postoperatively, her symptoms and hyperthyroidism resolved.
Thyrotropin-secreting pituitary adenomas are rare. Furthermore, recent reports suggest that 31% to 36% of adenomas may show evidence of secretion of multiple pituitary hormones. This case emphasizes the importance of considering pituitary causes of thyrotoxicosis and summarizes the clinical and pathology findings in a patient with a plurihormonal pituitary adenoma.