A survey of the use of ultrasound by small animal veterinary clinicians.

This study aimed to determine the current use of ultrasound amongst small animal veterinarians. A total of 1216 small animal veterinary practitioners responded to an electronic survey that was administered through the Veterinary Information Network to all its members. Descriptive statistics were generated; limited inferential statistics were performed to examine specific relationships. Eighty-four percent of respondents had access to an ultrasound unit, and 86% of respondents reported using their unit multiple times per week. The most common uses were assistance with cystocentesis (93%) and abdominocentesis (71%), pregnancy diagnosis (69%), limited abdominal evaluation (63%), to aid in thoracocentesis (59%), and limited thoracic evaluation (52%). Eighty-nine percent of respondents received some formal training in ultrasound, most commonly from continuing education courses. Most respondents (52%) reported receiving ≤25 h of training. Additionally, 88% of respondents believed it was either extremely or very important for there to be ultrasound training for veterinary students prior to graduation. Based on this survey, most small animal practitioners commonly use ultrasound for limited examinations, being most confident in the sonographic evaluation and centesis of the bladder and for the detection and centesis of effusion in a body cavity. With most respondents having ≤25 h of training in ultrasound, typically obtained in postgraduate courses, an expansion in standardized basic ultrasound training within the veterinary curriculum may be warranted.

Crystal structure of 1-{4-[bis-(4-methyl-phen-yl)amino]-phen-yl}ethene-1,2,2-tricarbo-nitrile.

The title compound, C25H18N4, crystallizes in the centrosymmetric ortho-rhom-bic space group Pbca, with eight mol-ecules in the unit cell. The main feature noticeable in the structure is the impact of the tri-cyano-vinyl (TCV) group in forcing partial planarity of the portion of the mol-ecule carrying the TCV group and directing the mol-ecular packing in the solid state, resulting in the formation of π-stacks of dimers within the unit cell. Short π-π stack closest atom-to-atom distances of 3.444 (15) Šare observed. Such motif patterns are favorable as they are thought to be conducive for better charge transport in organic semiconductors, which results in enhanced device performance. Intra-molecular charge transfer is evident from the shortening in the observed experimental bond lengths. The nitro-gen atoms (of the cyano groups) are involved in extensive short contacts, primarily through C-H⋯NC inter-actions with distances of 2.637 (17) Å.

COP1 controls light-dependent chromatin remodeling.

Light is a crucial environmental factor that impacts various aspects of plant development. Phytochromes, as light sensors, regulate myriads of downstream genes to mediate developmental reprogramming in response to changes in environmental conditions. CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1) is an E3 ligase for a number of substrates in light signaling, acting as a central repressor of photomorphogenesis. The interplay between phytochrome B (phyB) and COP1 forms an antagonistic regulatory module that triggers extensive gene expression reprogramming when exposed to light. Here, we uncover a role of COP1 in light-dependent chromatin remodeling through the regulation of VIL1 (VIN3-LIKE 1)/VERNALIZATION 5, a Polycomb protein. VIL1 directly interacts with phyB and regulates photomorphogenesis through the formation of repressive chromatin loops at downstream growth-promoting genes in response to light. Furthermore, we reveal that COP1 governs light-dependent formation of chromatin loop and limiting a repressive histone modification to fine-tune expressions of growth-promoting genes during photomorphogenesis through VIL1.

Distinct accessory roles of Arabidopsis VEL proteins in Polycomb silencing.

Polycomb repressive complex 2 (PRC2) mediates epigenetic silencing of target genes in animals and plants. In Arabidopsis, PRC2 is required for the cold-induced epigenetic silencing of the FLC floral repressor locus to align flowering with spring. During this process, PRC2 relies on VEL accessory factors, including the constitutively expressed VRN5 and the cold-induced VIN3. The VEL proteins are physically associated with PRC2, but their individual functions remain unclear. Here, we show an intimate association between recombinant VRN5 and multiple components within a reconstituted PRC2, dependent on a compact conformation of VRN5 central domains. Key residues mediating this compact conformation are conserved among VRN5 orthologs across the plant kingdom. In contrast, VIN3 interacts with VAL1, a transcriptional repressor that binds directly to FLC These associations differentially affect their role in H3K27me deposition: Both proteins are required for H3K27me3, but only VRN5 is necessary for H3K27me2. Although originally defined as vernalization regulators, VIN3 and VRN5 coassociate with many targets in the Arabidopsis genome that are modified with H3K27me3. Our work therefore reveals the distinct accessory roles for VEL proteins in conferring cold-induced silencing on FLC, with broad relevance for PRC2 targets generally.

GATA3 immunohistochemistry as a diagnostic adjunct for differentiated vulvar intraepithelial neoplasia: utility and limitations.

Herein, the authors evaluate the diagnostic utility and limitations of GATA3 immunohistochemistry for the distinction of differentiated vulvar intraepithelial neoplasia (dVIN) from its potential mimics. Immunohistochemical studies for GATA3, p53, and p16 were performed on 124 pathologic vulvar tissues, inclusive of dVIN (n = 21), vulvar aberrant maturation (n = 10), high-grade squamous intraepithelial lesion (HSIL) (n = 44), and 49 non-neoplastic vulvar dermatoses of various types. GATA3 expression was scored using a modification of previously proposed criteria: pattern 0 (no significant loss of basal layer staining, >75% staining), pattern 1 (25-75% staining), and pattern 2 (<25% staining). With the exception of lichen sclerosus, 8% of which showed pattern 1 or 2 staining, all other non-neoplastic lesions showed pattern 0 expression. Aberrant GATA3 expression (i.e., patterns 1 or 2) was present in 90% of dVIN cases (2 [9.5%], 3 [14.3%], 16 [76.2%] with patterns 0, 1, and 2 respectively), 90% of vulvar aberrant maturation cases (1 [10%],7 [70%], 2 [20%] with patterns 0, 1, and 2 respectively), and 15.9% of HSIL cases (84.1% pattern 0; 2.3% pattern 1; 13.6% pattern 2). All HSIL cases were p16 positive, including the 7 pattern 1 and 2 cases. All cases of dVIN-like HSIL were pattern 0, and all (n = 2) cases of HSIL-like (basaloid) dVIN were pattern 2 (both of the latter cases displayed complete absence of epidermal staining). Only 1 dVIN case was both pattern 0 and p53-wild-type. We conclude that GATA3 is useful for the distinction of dVIN from non-neoplastic dermatoses and from HSIL, but is best used as part of a panel that includes p53 and p16 to mitigate its limitations.

Extramammary Paget's Disease of the Vulva and Concomitant Premalignant/Malignant Vulvar Lesions: A Potential Challenge in Diagnosis and Treatment.

The aim of the present study was to evaluate the incidence of concomitant vulvar cancers or premalignant lesions in women surgically treated for extramammary Paget's disease of the vulva (EMPDV) through a multicenter case series. The medical records of all women diagnosed with and treated for EMPDV from January 2010 to December 2020 were retrospectively analyzed. Women with EMPDV and synchronous vulvar cancer, vulvar intraepithelial neoplasia (VIN) and/or lichen sclerosus (LS) at the histology report were included in the study. A total of 69 women eligible for the present study were considered. Concomitant vulvar lesions occurred in 22 cases (31.9%). A total of 11 cases of synchronous VIN (50%) and 14 cases (63.6%) of concomitant LS were observed. One patient (4.5%) had synchronous vulvar SCC (FIGO stage 1B). Women with EMPDV and concomitant premalignant/malignant vulvar lesions had a significantly higher rate of invasive EMPDV and wider lesions with an extravulvar involvement. The specific meaning of the association between EMPDV, VIN, SCC and LS remains unclear. The potential overlapping features between different vulvar lesions highlight the importance of dedicated gynecologists and pathologists in referral centers.

Pagetoid Squamous Intraepithelial Neoplasia of the Vulva as a Mimicker of Vulvar Extramammary Paget Disease: Two Cases with Basal Layer Sparing.

Human papillomavirus-associated vulvar intraepithelial neoplasia (high-grade squamous intraepithelial neoplasia [HSIL] or VIN of usual type) is a lesion characterized by atypia extending from the basal layer to the upper epidermis. There are only rare reports of vulvar intraepithelial morphology exhibiting a pagetoid pattern of intraepithelial dissemination. We herein report two cases of vulvar HSIL in which a pagetoid pattern of spread and a largely uninvolved basal layer represented a diagnostic pitfall for extramammary Paget disease. Nuclear atypia reminiscent of HSIL in addition to expression of p16, KRT5/6, and p40 were however in favor of pagetoid HSIL. Although there is morphological and immunohistochemical overlap between these two entities, an accurate diagnosis is important, since an erroneous diagnosis of vulvar extramammary Paget disease may lead to an extensive workup comprising radiological imaging, colonoscopy, and cystoscopy.

The First Human Vulvar Intraepithelial Neoplasia Cell Line with Naturally Infected Episomal HPV18 Genome.

Persistent infection with high-risk HPV leads to cervical cancers and other anogenital cancers and head and neck carcinomas in both men and women. There is no effective drug fortreating HPV infection and HPV-associated carcinomas, largely due to a lack of models of natural HPV infection and the complexity of the HPV life cycle. There are no available cell lines from vulvar, anal, or penile lesions and cancers in the field. In this study, we established the first human cell line from vulvar intraepithelial neoplasia (VIN) with naturally infected HPV18 by conditional reprogramming (CR) method. Our data demonstrated that VIN cells possessed different biological characteristics and diploid karyotypes from HPV18-positive cancer cells (HeLa). Then, we determined that VIN cells contained episomal HPV18 using approaches including the ratio of HPV E2copy/E7copy, rolling cycle amplification, and sequencing. The VIN cells expressed squamous epithelium-specific markers that are different from HeLa cells, a cervical adenocarcinoma cell line. When cultured under 3D air-liquid interface (ALI) system, we observed the expression of both early and late differentiation markers involucrin and filaggrin. Most importantly, we were able to detect the expression of viral late gene L1 in the cornified layer of ALI 3D culture derived from VIN cells, suggesting quite different HPV genomic status from cancer cells. We also observed progeny viral particles under transmission electron microscopy (TEM) in ALI 3D cultures, confirming the episomal HPV18 genome and active viral life cycle in the new cell line. To our knowledge, this is the first human VIN cell line with naturally infected HPV18 genome and provides a valuable model for HPV biology studies, HPV-associated cancer initiation and progression, and drug-screening platforms.

Vulval Intraepithelial Neoplasia 3: A Clinico-Pathological Review in a Tertiary Care Centre Over 10 Years.

Objectives: Vulval Intraepithelial Neoplasia 3 (VIN) is a chronic, premalignant condition affecting the vulval skin. The age standardised incidence is approximately one per 100,000 women, with a peak at 30-49 years of age, and has risen over recent decades. This study would analyse the pattern of presentation, diagnosis, treatment and follow up of patients diagnosed with VIN 3 over a period of ten years at a tertiary care centre in India. Materials and Methods: This was a retrospective study conducted on all patients diagnosed to have VIN 3 between 1 January 2010 to 30 November 2019 in the Department of Gynaecologic Oncology, Christian Medical College, Vellore were included in this study. The outpatient records of the patients were obtained from an electronic registry. Results: A total of 18 patients were diagnosed of VIN 3 during this time period. Sixteen patients were older than 50 years. Abnormal PAP was noted in 10 patients (HSIL-7, LSIL-2, ASC-H-1). Four patients had coexisting VAIN 3. About 16 patients underwent primary simple vulvectomy or wide local excision. Two patients were managed conservatively. Nine patients had recurrence with mean disease free interval of 12.5 months (4-36 months). Cryotherapy was used in 2 patients. Imiquimod was used in 3 patients. Surgical margins was achieved in 7 patients out of which 5 patients had recurrence. About 50% of patients with involved margins on biopsy had recurrence. Mean duration of follow up was 17 months (4-105 months). About 8 patients developed squamous cell carcinoma of genital tract on follow up. Conclusion: VIN 3 has a high rate of progression to invasive SCC. Regression of VIN is rare. Proper follow up and treatment of VIN 3 goes a long way in preventing the morbidity associated with vulval cancer.

Combination of surgery and laser for the treatment of extensive VIN3 and vulval condyloma: A case report.

Introduction and importance: Vulval intraepithelial neoplastic lesions (VINs) are rare lesions that appear with limited signs of pre-malignancy restricted to the vulvar epithelium. One of the principal causes of VINs is the human papillomavirus (HPV) infection, especially in people with weakened immune systems and young women. Case presentation: A 35-year-old woman presented with VIN3 who had severe immunosuppression and was under corticosteroid treatment. Her lesions were treated with a laser and surgical excision. Clinical discussion: Pathological findings indicated full thickness dysplasia and HPV infection. Follow-up after 5 years showed complete recovery and no recurrence, with a restoration of the vulva esthetics. Conclusion: Due to the increasing prevalence of VIN malignancy in young women and the importance of maintaining normal anatomy and function of the genitalia, a combination of surgery and laser can be used instead of extensive surgery only.

Diversity of soil fungi in the vineyards of Changli region in China.

This study aimed to elucidate the fungal diversity of Changli vineyard soil in China. High-throughput sequencing technology was used to investigate the diversity and composition of soil fungi in five vineyards from different geographical locations in Changli. Although the five vineyards had similar fungal communities, the diversity, composition, and distribution of the high-abundance species differed. Ascomycota, Basidiomycota, and Mortierellomycota were dominant phyla. Among the 14 high-abundance genera of fungi, Odiodendron, Pleotrichocladium, and Plectosephalella have rarely been reported in other vineyards and are unique to the Changli region. In addition, Solicoccozyma aeria and Solicoccozyma terrea were the dominant species in the five vineyards and have rarely been reported in domestic vineyards. Additionally, Rhizophagus, Wardomyces, Mortierella, Volutella, and Cryptococcus were significantly different among the five vineyard soils. Among these species, Mortierella was highly abundant in each vineyard, but its contents were significantly different across vineyards. These findings enrich the information on the composition and diversity of soil fungi in the vineyard of the Changli region, which helps to explore the regional or distinctive sensorial attributes of wine from the perspective of microbial biogeography.

[Vulvar intraepithelial neoplasias]. / Les néoplasies intraépithéliales vulvaires.

Vulvar squamous cell carcinoma arises from precursor lesions: vulvar intraepithelial neoplasias (VIN). Most of them are caused by the human papillomavirus (HPV), and the precursor lesion for this group is VIN usual type/high grade squamous intraepithelial lesion (uVIN/HSIL) of variable clinical presentation and having a light invasive potential. Some VIN are HPV-independent and arise in older women against the background of chronic dermatoses, mostly lichen sclerosus. Their histological diagnosis is more subtle. They have a higher invasive potential. A third precursor, leading to well-differentiated, or even verrucous, carcinomas, is still ill-defined to this day. We detail these lesions' clinics, histology, and biomarkers (immunohistochemical and molecular).

[Advocacy for food and wine in palliative care]. / Plaidoyer pour la nourriture et le vin en soins palliatifs.

In the palliative care unit, the care and treatment provided are aimed at optimizing the quality of life and not the quantity of life. Food is adjusted to the patient's condition and is primarily oriented towards pleasure food.

COVISHIELD (AZD1222) VaccINe effectiveness among healthcare and frontline Workers of INdian Armed Forces: Interim results of VIN-WIN cohort study.

BACKGROUND: On 16 Jan 2021, India launched its immunization program against COVID-19. Among the first recipients were 1.59 million Health Care Workers (HCWs) and Frontline Workers (FLWs) of the Indian Armed Forces, who were administered COVISHIELD (Astra Zeneca). We present an interim analysis of vaccine effectiveness (VE) estimates till 30 May 2021. METHODS: The VIN-WIN cohort study was carried out on anonymized data of HCWs and FLWs of Indian Armed Forces. The existing surveillance system, enhanced for COVID-19 monitoring, was sourced for data. The cohort transitioned from Unvaccinated (UV) to Partially Vaccinated (PV) to Fully Vaccinated (FV), serving as its own internal comparison. Outcomes studied in the three groups were breakthrough infections and COVID related deaths. Incidence Rate Ratio (IRR) was used to compare outcomes among the three groups to estimate VE. RESULTS: Data of 1,595,630 individuals (mean age 27.6 years; 99% male) over 135 days was analysed. Till 30 May 21, 95.4% and 82.2% were partially and fully vaccinated. The UV, PV and FV compartments comprised 106.6, 46.7 and 58.7 million person-days respectively. The number of breakthrough cases in the UV, PV and FV groups were 10061, 1159 and 2512; while the deaths were 37, 16 and 7 respectively. Corrected VE was 91.8-94.9% against infections. CONCLUSION: Interim results of the VIN-WIN cohort study of 1.59 million HCWs and FLWs of Indian Armed Forces showed a ∼93% reduction in COVID-19 breakthrough infections with COVISHIELD vaccination.

Localized amyloidosis in usual-type vulvar intraepithelial neoplasia: High-risk HPV association and potential clinical significance. A series of 45 cases.

Localized cutaneous amyloidosis was reported recently in association with vulvar squamous intraepithelial neoplasia (VIN). High-risk human papillomavirus (hrHPV) type 16 is the most commonly reported subtype found in usual-type VIN. However, it is unknown whether any hrHPV subtype(s) is/are prevalent in simultaneous squamous intraepithelial lesions and localized amyloidosis in the same individual - the subject matter of this report. To observe the potential clinical significance, study cases were followed and compared to usual-type VINs without amyloid deposition. Of 45 patients of usual-type VINs associated with amyloidosis, 33 had detectable hrHPV, and 12 were negative. HPV 16 alone or in combination with HPV 31 accounted for 72%, HPV 51 alone accounted for 2% of the cases, and 26% were negative for hrHPV. Lack of demonstrable hrHPV in a significant proportion of cases (26%) raises the possibility of a novel or presently undetected hrHPV subtype. Five of the total 22 (23%) patients with amyloid had either Squamous cell carcinoma or high-grade VIN on follow-up. In contrast, 14 of 18 (78%) patients exhibiting lesions without amyloid had disease on follow-up. These findings may indicate that amyloid deposition may represent a feature of regression or a potential favorable prognostic indicator.

Putative precancerous lesions of vulvar squamous cell carcinoma.

Precursor lesions of vulvar squamous cell carcinoma (VSCC) can be divided into two major biologic and prognostic groups: HPV-associated and HPV-independent VSCC. These two pathways are categorized as usual vulvar intraepithelial neoplasia (uVIN) with progression to basaloid or warty VSCC and differentiated vulvar intraepithelial neoplasia (dVIN) with progression to the more common keratinizing VSCC. While the HPV-dependent pathway to squamous cell carcinoma is well-understood, the development of squamous cell carcinoma from HPV-independent lesions is less clear. The majority of HPV-independent lesions fall into the dVIN category, and mutations in TP53 have been implicated as the driver behind their development. Other less common HPV-independent precursor lesions, termed differentiated exophytic vulvar intraepithelial lesion (DEVIL) and vulvar acanthosis with altered differentiation (VAAD), have also been characterized as precursors to keratinizing and verrucous VSCC. Inflammatory conditions of the vulva such as lichen sclerosus and lichen simplex chronicus also put patients at risk for developing VSCC. We herein evaluate the available evidence and biologic basis for these VSCC precursor lesions, among other speculated entities, and discuss their clinical, diagnostic, and prognostic features.

Identification of the Volatile Compounds and Sensory Attributes of Long-Term Aging Vin Santo Wine from Malvasia di Candia Aromatic Grapes.

In an effort to offer a contribution to fill the gap of knowledge about the relationship between the sensory properties and aromatic profile of Malvasia grapes, the present work was aimed at evaluating volatile compounds, aroma, and sensory attributes of long-term aging (15 years) Vin Santo wine obtained from Malvasia di Candia aromatica grapes. In this article, the aromatic profile are studied using gas chromatography-mass spectrometry (GC-MS), gas chromatography with flame ionization detection (GC-FID), and sensory analysis by involving a panel of trained assessors to explore the sensory profile resulting after long-term aging (up to 15 years). The GC-MS and GC-FID analyses of wines allowed the identification and semi-quantification of twenty-seven volatiles belonging to 12 conventional groups of compounds. From a sensory perspective, the Vin Santo wines analyzed in this study presented a very complex sensory profile characterized by 19 sensory descriptors of which 14 related to olfactory terms. The relationship between sensory and GC-FID data deduced from three samples representing nearly three years in the past 15 years was investigated by means of Partial Least Square (PLS) modeling, showing that specific volatile compounds could predict a specific orthonasal and/or retronasal odor perceived by the trained panel of assessors, clearly differentiating the Vin Santo vintages. Identifying the main volatiles and aromas of long-term Vin Santo wine may be helpful to winemakers, since wine aging sensory properties are often associated with a prestigious image and contribute to defining wine quality.

The peptidyl-prolyl isomerases FKBP15-1 and FKBP15-2 negatively affect lateral root development by repressing the vacuolar invertase VIN2 in Arabidopsis.

MAIN CONCLUSION: The peptidyl-prolyl isomerases FKBP15-1 and FKBP15-2 negatively modulate lateral root development by repressing vacuolar invertase VIN2 activity. Lateral root (LR) architecture greatly affects the efficiency of nutrient absorption and the anchorage of plants. Although the internal phytohormone regulatory mechanisms that control LR development are well known, how external nutrients influence lateral root development remains elusive. Here, we characterized the function of two FK506-binding proteins, namely, FKBP15-1 and FKBP15-2, in Arabidopsis. FKBP15-1/15-2 genes were expressed prominently in the vascular bundles of the root basal meristem region, and the FKBP15-1/15-2 proteins were localized to the endoplasmic reticulum of the cells. Using IP-MS, Co-IP, and BiFC assays, we demonstrated that FKBP15-1 and FKBP15-2 interacted with vacuolar invertase 2 (VIN2). Compared to Col-0 and the single mutants, the fkbp15-1fkbp15-2 double mutant had more LRs, and presented higher sucrose catalytic activity. Moreover, genetic analysis showed genetic epistasis of VIN2 over FKBP15-1/FKBP15-2 in controlling LR development. Our results indicate that FKBP15-1 and FKBP15-2 participate in the control of LR number by inhibiting the catalytic activity of VIN2. Owing to the conserved peptidylprolyl cis-trans isomerase activity of FKBP family proteins, our results provide a clue for further analysis of the interplay between lateral root development and protein modification by FKBPs.