Comparison of the incidence of intra-operative haemorrhage from ovarian vessels during ovariectomy and ovariohysterectomy of dogs and cats performed by inexperienced surgeons using surgeon's and constrictor knots.

AIMS: To compare the incidence of intra-operative haemorrhage from ovarian vessels during ovariectomy (OV) and ovariohysterectomy (OVH) in dogs and cats performed by inexperienced surgeons using surgeon's and constrictor knots to ligate the ovarian pedicles. METHODS: All client-owned female dogs (n = 51) and cats (n = 102) that presented for OV or OVH at two referral clinics in Belgium and France from January to June 2019 were included. Surgeries were performed by inexperienced surgeons under the supervision of diplomates or residents of the European College of Veterinary Surgeons. During routine and emergency OV or OVH one pedicle of each animal was ligated using a constrictor knot and the other with a surgeon's knot, the side assigned randomly. Time taken to perform each knot and the number of ligatures that resulted in intraoperative haemorrhage from the ovarian vessels were recorded. Body condition score (BCS) was recorded for 33 dogs and 22 cats. RESULTS: The median time taken to perform constrictor knots in dogs (81 seconds), was longer than for surgeon's knots (69 seconds; p = 0.005). In cats, the median time taken to perform constrictor knots (109 seconds) was also longer than for surgeon's knots (90.5 seconds; p = 0.02).The number of dogs that had intra-operative haemorrhages from pedicles ligated with constrictor knots (2/102; 3.9%) was less than those ligated with surgeon's knots (10/102; 19.6%; p = 0.027). The median BCS of dogs that experienced haemorrhage (n = 8; median 5/9, min 3/9, max 7/9) was higher (p = 0.019) than that of dogs that did not experience haemorrhage (n = 25; median 4/9, min 3/9, max 8/9).There was no evidence (p = 1.0) of a difference in the proportion of cats that experienced intra-operative haemorrhage from pedicles ligated with constrictor knots (3/44; 6.8%) and those ligated with surgeon's knots (2/44; 4.5%). Two-thirds of the haemorrhages with constrictor knots were caused by pedicle rupture during tightening. CONCLUSIONS: The rate of intraoperative haemorrhage from the ovarian pedicle was lower when a constrictor knot was used compared to a surgeon's knot in dogs but not in cats. While the constrictor knot was more time consuming to tie this is not likely to have a clinical impact. Use of this knot by inexperienced surgeons in dogs may help to reduce the risk of intraoperative haemorrhage during OVH/OV.

Use of Soft Contact Lens for Esthetic and Functional Rehabilitation.

OBJECTIVE: To report the outcomes and complications of colored soft contact lenses (SCLs) to improve esthetic or eye function in visually impaired (VI) or blind patients. METHODS: This retrospective study enrolled consecutive patients with unilateral or bilateral VI or blindness who had received colored SCLs to improve appearance or ocular function. Data were collected on demographics, complaints, complete ophthalmological examinations, types of SCL, follow-ups, and complications. RESULTS: The study sample was comprised of 109 patients (ages 4-80 years). Eighty-six patients (78.89%) had unilateral blindness, and 14 patients (12.84%) had functional disorder. Most of the patients presenting for improved esthetic had anterior segment pathology (74/67.88%), mainly secondary to trauma (55/50.5%) resulting in leukoma (73/66.97%). Patients with functional VI (19/17.43%) received filtered SCLs for color blindness (7/6.42%), diplopia (7/6.42%), or photophobia (5/4.58%). No serious complications were observed in any cases, and 94.49% of patients were satisfied with the SCLs. CONCLUSION: Colored SCLs can cover ocular surface imperfections in VI or blind eyes of patients who are seeking better cosmesis or improvement functional VI. Soft contact lenses with only one filter can cover imperfections of the ocular surface and improve vision in functional VI. Appropriate follow-up of these patients can reduce complication rates, resulting in good cosmesis and patient satisfaction with a positive impact on the lives of patients suffering from functional VI or blindness.

Gut microbiota and immunity in common variable immunodeficiency: crosstalk with pro-inflammatory cytokines.

In recent years, gut microbiota (GM) has emerged as a key factor in shaping the pathogenesis of a vast array of immune-mediated diseases, as well as in the response to immune-based treatments such as anti PD-1 and anti-CTLA4 therapy or influenza vaccination. In addition, GM has a significant role in the immune system development and is fundamental in developing mucosal immunity. Recent data suggest that GM plays an important role in the immune system of immune deficient patients. GM status has a remarkable impact on the immune system and in immune deficient patients; this can lead to important consequences. Prebiotics are indeed a promising candidate in restoring GM homeostasis and improving immunity. Antibiotics are also capable of altering the microbial equilibrium.

ATP in the tumour microenvironment drives expression of nfP2X7, a key mediator of cancer cell survival.

The ATP-gated receptor P2X7 is expressed in multiple malignant tumours including neuroblastoma, melanoma, prostate, lung and breast. P2X7 has a significant role in mediating diverse cell responses, which upon dysregulation are associated with tumour initiation and development. The rapid, ATP-mediated activation of P2X7 induces a fast-inward cation current in cells. However, prolonged ATP-mediated activation of P2X7 leads to formation of a pore that increases membrane permeability and eventually causes cell death. This presents a potential paradox, as the tumour microenvironment contains extracellular ATP at levels sufficient to activate the P2X7 pore and trigger cell death. However, P2X7 expression is associated with enhanced cancer cell survival, proliferation and metastatic potential. At least one distinct conformational form of P2X7, termed non-pore functional P2X7 (nfP2X7), has been described, which is not able to form a functional pore. We demonstrate for the first time in this study that exposure to a high ATP concentration, equivalent to those measured in the tumour microenvironment, drives nfP2X7 expression and also that nfP2X7 is essential for tumour cell survival. We show that monoclonal antibodies raised against a P2X7 amino acid sequence (200-216), whose conformation is distinct from that of wild-type (WT) P2X7, bind specifically to nfP2X7 expressed on the surface of tumour cells. We also show that nfP2X7 is broadly expressed in patient-derived tumour sections from a wide range of cancers. Therefore, antibodies raised against E200 provide tools that can differentiate between forms of the P2X7 receptor that have a key role in cancer.

Can Volumetric and Morphological Variants of Sphenoid Sinuses Influence Sinuses Opacification?

Improvements in computed tomography and in functional endoscopic sinus surgery have recently increased interest toward paranasal sinus anatomy and anatomic variations that can be observed in patients affected by sinusitis. Isolated sphenoid sinusitis is a relatively rare pathology, often related to nonspecific symptoms, therefore making diagnosis difficult. The correlation between this type of sinusitis and anatomical variants remains unclear.The authors' aim was to retrospectively revise paranasal sinuses computed tomography scans of patients affected by sphenoid sinusitis, compared with a control group, analyzing the types of sphenoid sinus and the presence of aberrant pneumatization, and performing a segmentation of the sphenoid sinuses to calculate the volumes.Sphenoid sinuses of 60 patients affected by sinus opacification, compared with a control group, were segmented. Type of sinus (sellar, presellar, postsellar) and presence of aberrant pneumatization were assessed as well. Possible statistically significant differences in volumes according to sex and group were assessed through 2-way ANOVA test (P < 0.05). Post-hoc test was assessed through Student t test. χ test was applied in order to verify the statistically significance of differences in frequency of different types of sinus pneumatization variants (P < 0.05).Average volume of sphenoid sinuses in males was of 7.672 cm and of 7.751 cm in females within the group of patients; statistically significant differences in volume were found according to sex (P: 0.342), but not between the patients and control group (P: 0.0929). Post-hoc test verified that males affected by sinus opacification showed smaller volumes in comparison with the control males (P < 0.05). In addition, patients by affected sinus opacification showed more frequently the postsellar type and were less affected by pneumatization variants of the sphenoid bone than the control group (P < 0.05).This study first suggests the possible protective role of variants of pneumatization in the development of sphenoid sinus opacification.

Anatomical Uniqueness of Ear Morphology: A Novel Metrical Approach through Three-Dimensional Superimposition.

Uniqueness of ear morphology has been a widely debated issue in cephaloscopy, but past studies used only two-dimensional approaches. In the current investigation, the right and left ears of 10 healthy adults were imaged twice by stereophotogrammetry at the interval of a few seconds. The ear images obtained from the two acquisitions were superimposed both within subject (group of matches) and among subjects (group of mismatches). A point-to-point root mean square distance was calculated between the two three-dimensional models. Differences according to side and group were assessed by two-way analysis of variance. In total, 200 superimpositions were performed. On average, the point-to-point root mean square distance was 0.31 mm in cases of matches and 1.43 mm in cases of mismatches: differences were statistically significant (p < 0.01). Results provided quantitative data for the assessment of uniqueness of ear morphology, highlighting differences based on their three-dimensional morphology.

Application of 3D models of palatal rugae to personal identification: hints at identification from 3D-3D superimposition techniques.

Palatal rugae are known in literature as individualizing anatomical structures with a strong potential for personal identification. However, a 3D assessment of their uniqueness has not yet been performed. The present study aims at verifying the uniqueness of 3D models of the palate. Twenty-six subjects were recruited among the orthodontic patients of a private dental office; from every patient, at least two dental casts were taken in different time periods, for a total of 62 casts. Dental casts were digitized by a 3D laser scanner (iSeries, Dental Wings©, Montreal, Canada). The palatal area was identified, and a series of 250 superimpositions was then performed automatically through VAM©software in order to reach the minimum point-to point distance between two models. In 36 matches the models belonged to the same individual, whereas in 214 mismatches they came from different subjects. The RMS (root mean square) of point-to-point distances was then calculated by 3D software. Possible statistically significant differences were assessed through Mann-Whitney test (p < 0.05). Results showed a statistically significant difference in RMS mean point-to-point distance between matches (mean 0.26 mm; SD 0.12) and mismatches (mean 1.30; SD 0.44) (p < 0.0001).All matches reached an RMS value below 0.50 mm. This study first provided an assessment of uniqueness of palatal rugae, based on their anatomical 3D conformations, with consequent applications to personal identification.

Vertebral Tortuosity Index in Patients with Non-Connective Tissue Disorder-Related Aneurysm Disease.

OBJECTIVE: The vertebral tortuosity index (VTI) predicts increased risk of acute aortic events in patients with known genetic aortopathies. This study describes the VTI in a cohort of patients with non-connective tissue disorder-related large aneurysms. METHODS: Hospital imaging records from July 2012 to March 2016 were interrogated to identify patients with aneurysmal disease who had undergone computed tomographic angiography that included imaging of vertebral arteries. A control group of consecutive patients undergoing carotid and vertebral imaging was also assessed. VTI was calculated using the formula: [(centre-line distance) / (straight-line distance)-1] ×100 for all patients, and statistical analysis undertaken to determine whether measured VTI was statistically different in patients of younger age, with larger aneurysms, or an acute presentation. Comparison was made with patients who had no aneurysm disease. RESULTS: Sixty-five patients were identified with adequate imaging to assess the entire aorta, including vertebral arteries. The majority of patients were male (71%, 46/65) and mean age at the time of the CT scan was 71 years (SD 11.1 years). There were 11 patients under the age of 60 years in this cohort. The mean VTI was 33.17 (SD 20.43). There was no statistically significant difference between different territories of presentation (proximal vs. distal aneurysm, p=.94), age of patient (>60 years vs. <60 years, p=.2), or size of aneurysm (>6 cm vs. <6 cm, p=.09). Acuity of presentation was not predicted by a higher VTI (p=.69). The VTI in patients with aneurysms was higher than in patients without aneurysm disease (VTI = 16.1, p<.005) CONCLUSIONS: An elevated VTI is consistently present in patients with degenerative aneurysms and has potential as a universally available predictive measurement. However, the increased VTI in the older cohort without connective tissue disease may not carry the same predictive value for acute presentations as has been demonstrated in younger patients with a known genetic basis for their aortopathy.

Extracellular purines, purinergic receptors and tumor growth.

Virtually, all tumor cells as well as all immune cells express plasma membrane receptors for extracellular nucleosides (adenosine) and nucleotides (ATP, ADP, UTP, UDP and sugar UDP). The tumor microenvironment is characterized by an unusually high concentration of ATP and adenosine. Adenosine is a major determinant of the immunosuppressive tumor milieu. Sequential hydrolysis of extracellular ATP catalyzed by CD39 and CD73 is the main pathway for the generation of adenosine in the tumor interstitium. Extracellular ATP and adenosine mold both host and tumor responses. Depending on the specific receptor activated, extracellular purines mediate immunosuppression or immunostimulation on the host side, and growth stimulation or cytotoxicity on the tumor side. Recent progress in this field is providing the key to decode this complex scenario and to lay the basis to harness the potential benefits for therapy. Preclinical data show that targeting the adenosine-generating pathway (that is, CD73) or adenosinergic receptors (that is, A2A) relieves immunosuppresion and potently inhibits tumor growth. On the other hand, growth of experimental tumors is strongly inhibited by targeting the P2X7 ATP-selective receptor of cancer and immune cells. This review summarizes the recent data on the role played by extracellular purines (purinergic signaling) in host-tumor interaction and highlights novel therapeutic options stemming from recent advances in this field.

Chitosan-pectin hybrid nanoparticles prepared by coating and blending techniques.

The preparation of chitosan nanoparticles in combination with pectins, as additional mucoadhesive biopolymers, was investigated. Pectins from apple and from citrus fruit were considered; polygalacturonic acid was taken as a reference. Tripolyphosphate was used as an anionic cross-linker. Two different techniques were compared, namely the coating and the blending. Coated nanoparticles (NPs) in the ratio pectin:NPs from 2:1 to 5:1 evidenced that the size of NPs increased as the amount of pectin (both from apple and citrus fruit) was increased. In particular, for NPs coated with pectin from citrus fruit the size ranges from 200 to 260nm; while for NPs coated with pectin from apple the size ranges from 330 to 450nm. A minimum value of Z-potential around -35mV was obtained for the ratio pectin:NPs 4:1, while further addition of pectin did not decrease the Z-potential. Also blended NPs showed a dependence of the size on the ratio of the components: for a given ratio pectin:tripolyphosphate the size increases as the fraction of chitosan increases; for a low ratio chitosan:pectin a high amount of tripolyphosphate was needed to obtain a compact structure. The effect of the additional presence of loaded proteins in chitosan-pectin nanoparticles was also investigated, since proteins contribute to alter the electrostatic interactions among charged species. FT-IR and DSC characterization are presented to confirm the interactions between biopolymers. Finally, the biocompatibility of the used materials was assessed by the chorioallantoic membrane assay, confirming the safety of the materials.

Age-related and sex-related changes in the normal soft tissue profile of native Northern Sudanese subjects: a cross-sectional study.

Information about age-related and sex-related normative measurements of the nasolabial region in native Northern Sudanese subjects is scanty. We have therefore used a hand-held laser scanner to measure nasolabial angles and distances, and collected the 3-dimensional coordinates of seven landmarks on the facial soft tissues from 654 healthy native Northern Sudanese subjects (327 male and 327 female, aged 4-30 years). From these we calculated five angles and two linear distances and took the mean (SD) for age and sex, and compared them using factorial analysis of variance. All measurements analysed were significantly modified by age in both sexes (p < 0.01) except for the distance from the lower lip to Ricketts' E-line. Sex had a significant effect on the mentolabial and maxillary prominence angles and both distances (p < 0.005). Nasal convexity and the interlabial angle became more obtuse with growth, while the nasolabial and mentolabial angles reduced progressively with female subjects having significantly more obtuse mentolabial angles (p < 0.001). The maxillary prominence angle progressively decreased during childhood, and increased after adolescence, with larger values in male subjects. The upper and lower lip distances from Ricketts' E-line were also significantly larger in male subjects (p < 0.003), but the difference reduced with age. Overall, there were several differences when we compared our data with published data for African and white subjects, which points to the need for ethnic-specific data. Measurements collected in the current study could be used for the quantitative description of facial morphology in native Northern Sudanese children, adolescents, and young adults.

Comparison of soft-tissue orbital morphometry in attractive and normal Italian subjects.

OBJECTIVE: To identify esthetic characteristics of the orbital soft tissues of attractive Italian adult women and men. MATERIALS AND METHODS: Three-dimensional computerized digitizers were used to collect the coordinates of facial landmarks in 199 healthy, normal subjects aged 18 to 30 years (71 women, 128 men; mean age, 22 years) and in 126 coetaneous attractive subjects (92 women, 34 men; mean age, 20 years) selected during beauty competitions. From the landmarks, six linear distances, two ratios, six angles, and two areas were calculated. Attractive subjects were compared with normal ones by computing z-scores. RESULTS: Intercanthal width was reduced while eye fissure lengths were increased in both genders. Orbital heights (os-or) were increased only in attractive women, with a significant gender-related difference. The inclinations of the eye fissure were increased in attractive subjects, while the inclinations of the orbit were reduced. For several of the analyzed measurements, similar patterns of z-scores were observed for attractive men and women (r  =  .883). CONCLUSION: Attractive women and men had several specific esthetic characteristics in their orbital soft tissues; esthetic reference values can be used to determine optimal goals in surgical treatment.

Iron bioavailability of common beans (Phaseolus vulgaris L.) intrinsically labeled with (59)Fe.

A radiobioassay was performed in rats with or without iron depletion to evaluate the iron bioavailability of diets enriched with common beans and with "multimixture", a nutritional supplement based on parts of foods that are not usually eaten. The full-body (59)Fe level was determined after 5h, the absorbed (59)Fe level was determined after 48 h, and the amount of (59)Fe retained was determined after 7 days. Iron bioavailability was assessed by the full-body radioactivity of the animals, determined using a solid scintillation detector. The iron bioavailability of common beans was higher in the iron-depleted animals (55.7%) than in the non-depleted animals (25.12%) because of the higher absorption rate in the iron-depleted animals. The multimixture did not influence dietary iron bioavailability. In addition, the iron bioavailability of common beans was similar to that observed in the standard source of iron for Wistar rats. Hence, common beans may be considered an adequate dietary iron source because of its high bioavailability.

ATP/P2X7 axis modulates myeloid-derived suppressor cell functions in neuroblastoma microenvironment.

Tumor microenvironment of solid tumors is characterized by a strikingly high concentration of adenosine and ATP. Physiological significance of this biochemical feature is unknown, but it has been suggested that it may affect infiltrating immune cell responses and tumor progression. There is increasing awareness that many of the effects of extracellular ATP on tumor and inflammatory cells are mediated by the P2X7 receptor (P2X7R). Aim of this study was to investigate whether: (i) extracellular ATP is a component of neuroblastoma (NB) microenvironment, (ii) myeloid-derived suppressor cells (MDSCs) express functional P2X7R and (iii) the ATP/P2X7R axis modulates MDSC functions. Our results show that extracellular ATP was detected in NB microenvironment in amounts that increased in parallel with tumor progression. The percentage of CD11b(+)/Gr-1(+) cells was higher in NB-bearing mice compared with healthy animals. Within the CD11b/Gr-1(+) population, monocytic MDSCs (M-MDSCs) produced higher levels of reactive oxygen species (ROS), arginase-1 (ARG-1), transforming growth factor-ß1 (TGF-ß1) and stimulated more potently in vivo tumor growth, as compared with granulocytic MDSCs (G-MDSCs). P2X7R of M-MDSCs was localized at the plasma membrane, coupled to increased functionality, upregulation of ARG-1, TGF-ß1 and ROS. Quite surprisingly, the P2X7R in primary MDSCs as well as in the MSC-1 and MSC-2 lines was uncoupled from cytotoxicity. This study describes a novel scenario in which MDSC immunosuppressive functions are modulated by the ATP-enriched tumor microenvironment.

Facial soft-tissue volumes in adult Northern Sudanese individuals with Down syndrome.

OBJECTIVE: To investigate dimensions and ratios of soft-tissue facial volumes of adult Northern Sudanese subjects with Down syndrome by using computerized anthropometric measurements. DESIGN, SETTING, AND PATIENTS: The 3D coordinates of soft-tissue facial landmarks were obtained by a computerized digitizer in 26 Northern Sudanese adult subjects with Down syndrome (18 men, 8 women, aged 17-34 years), and in 99 healthy Northern Sudanese controls (48 women, 51 men) of the same age range. From the landmarks, several facial volumes and volume ratios were calculated. Data were compared to those collected in healthy individuals by computing z-scores. RESULTS: In subjects with Down syndrome, facial volumes were significantly smaller than in control subjects (Student's t, p < 0.05). The patterns of deviation from the norm were similar in men and women. When compared to controls, subjects with Down syndrome had no differences in nose volume as a fraction of total facial volume and a larger total lip volume as a fraction of total facial volume; within the facial middle third, they had relatively larger upper lip volumes and relatively smaller nose volumes. CONCLUSIONS: The facial soft-tissue structures of subjects with Down syndrome differed from those of normal controls of the same age, sex and ethnic group: a reduced facial size was coupled with specific variations in the nasal and labial regions.

The labial aging process: a surface analysis-based three-dimensional evaluation.

BACKGROUND: With increasing age, the smile becomes elongated and less appealing. Currently, several methods are proposed for analysis of lip morphology including lateral cephalograms, profile and frontal photographs, video images, and three-dimensional systems. Despite several descriptions of morphologic and histologic age-related changes in the literature, no scientific well-supported model of the labial aging process is reported. METHODS: For this study, 33 healthy volunteers were selected and divided into two groups according to age: a youthful group (ages 21-34 years) and an aged group (ages 45-65 years). Their dental and labial stone casts were obtained, digitized, and virtually reproduced using a computerized electromechanical digitizer and applying nonuniform rational B-spline geometry. To obtain a synthetic parameter describing local surface deformation, average curvature and curvature variability indexes were computed and compared. RESULTS: No significant age- or sex-related differences in the average curvature were detected. In contrast, the curvature variability was significantly greater in the young than in the aged subjects. CONCLUSIONS: The labial arch surface remains macroscopically constant between the third and the sixth decades of life, but with local modifications that influence the standard deviation of its curvature. A high standard deviation described the protruding labial appearance of the young subjects, whereas a reduced one described the flat lips of the aged subjects. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .