Case of Anorchia in a Mixed-Breed Dog

Anorchia is a rare and often poorly understood disorder of sexual development. In the present case report, we used a multidisciplinary approach to diagnose a case of anorchia in a 30-month old dog. The diagnostic process began with gathering the dog medical history followed by a clinical visit with the patient, which included a general wellness examination as well as an examination of the genital system. As suggested in the relevant literature, the dog underwent an ultrasound and then computed tomography (CT) of the genital system, which confirmed the diagnosis of testicular agenesis. Genetic testing confirmed the male XY karyotype. Hormone testing also supported the diagnosis: testosterone and anti-M€ullerian hormone levels were below their reference ranges, and luteinizing hormone (LH) was above 1 ng/mL. Following the diagnostic procedures suggested in the relevant literature, the present study confirms anorchia in the dog and describes a case of testicular agenesis in the canine species

Efficacy of dupilumab in atopic comorbidities associated with moderate-to-severe adult atopic dermatitis

Background: Dupilumab is an anti-IL-4Rα antibody used in the treatment of patients with moderate-to-severe atopic dermatitis (msAD). This study explored the potential benefit of dupilumab in perennial allergic rhinoconjunctivitis (PAR) and perennial allergic asthma (PAA) caused by indoor allergens in adults with msAD. Methods: This multicentric, prospective, observational, real-life study included adult patients with msAD who had been treated with dupilumab in 16 Italian care centres. Efficacy outcomes regarding AD, PAR and PAA were collected at baseline and 16 weeks. Safety was also assessed. Results: We enrolled 123 patients with msAD. Between baseline and 16 weeks of treatment, the following measurements decreased statistically significantly: Eczema Area and Severity Index, SCOring AD, Patient-Oriented Eczema Measure, pruritus score, sleep score, Dermatology Life Quality Index and IgE. Dupilumab treatment in patients with comorbid PAR (n = 41) was associated with significant improvements in PAR disease control (measured using a Rhinitis Control Scoring System) and in PAR Quality of life (QoL) (measured using the Rhinoconjunctivitis QoL Questionnaire scores). In 32 patients with comorbid PAA, dupilumab significantly improved PAA control (measured using the Asthma Control Test and five-item Asthma Control Questionnaire scores) and disease-related QoL (measured using the Asthma QoL Questionnaire scores). Thirty-five patients (28.5%) developed conjunctivitis during the study period. Conclusion: These results support the benefits of dupilumab for adult patients with PAR and/or PAA associated with msAD

Growth hormone secretagogues exert differential effects on skeletal muscle calcium homeostasis in male rats depending on the peptidyl/non-peptidyl structure

TheorexigenicandanaboliceffectsinducedbyghrelinandthesyntheticGHsecretagogues(GHSs) are thought to positively contribute to therapeutic approaches and the adjunct treatment of a number of diseases associated with muscle wasting such as cachexia and sarcopenia. However, manyquestionsaboutthepotentialutilityandsafetyofGHSsinboththerapyandskeletalmuscle functionremainunanswered.Byusingfura-2cytofluorimetrictechnique,wedeterminedtheacute effectsofghrelin,aswellasofpeptidylandnonpeptidylsyntheticGHSsoncalciumhomeostasis, a critical biomarker of muscle function, in isolated tendon-to-tendon male rat skeletal muscle fibers.ThesyntheticnonpeptidylGHSs,butnotpeptidylghrelinandhexarelin,wereabletosignificantlyincreaserestingcytosoliccalcium[Ca2]i.ThenonpeptidylGHS-induced[Ca2] iincrease was independent of GHS-receptor 1a but was antagonized by both thapsigargin/caffeine and cyclosporineA,indicatingtheinvolvementofthesarcoplasmicreticulumandmitochondria.EvaluationoftheeffectsofapseudopeptidylGHSandanonpeptidylantagonistoftheGHS-receptor 1a together with a drug-modeling study suggest the conclusion that the lipophilic nonpeptidyl structureofthetestedcompoundsisthekeychemicalfeaturecrucialfortheGHS-inducedcalcium alterationsintheskeletalmuscle.Thus,syntheticGHSscanhavedifferenteffectsonskeletalmuscle fibersdependingontheirmolecularstructures.Thecalciumhomeostasisdysregulationspecifically induced by the nonpeptidyl GHSs used in this study could potentially counteract the beneficial effects associated with these drugs in the treatment of muscle wasting of cachexia- or other age-related disorders

Investigation of Radiation-Induced Toxicity in Head and Neck Cancer Patients through Radiomics and Machine Learning: A Systematic Review

Background. Radiation-induced toxicity represents a crucial concern in oncological treatments of patients affected by head and neck neoplasms, due to its impact on survivors' quality of life. Published reports suggested the potential of radiomics combined with machine learning methods in the prediction and assessment of radiation-induced toxicities, supporting a tailored radiation treatment management. In this paper, we present an update of the current knowledge concerning these modern approaches. Materials and Methods. A systematic review according to PICO-PRISMA methodology was conducted in MEDLINE/PubMed and EMBASE databases until June 2019. Studies assessing the use of radiomics combined with machine learning in predicting radiation-induced toxicity in head and neck cancer patients were specifically included. Four authors (two independently and two in concordance) assessed the methodological quality of the included studies using the Radiomic Quality Score (RQS). The overall score for each analyzed study was obtained by the sum of the single RQS items; the average and standard deviation values of the authors' RQS were calculated and reported. Results. Eight included papers, presenting data on parotid glands, cochlea, masticatory muscles, and white brain matter, were specifically analyzed in this review. Only one study had an average RQS was ≤ 30% (50%), while 3 studies obtained a RQS almost ≤ 25%. Potential variability in the interpretations of specific RQS items could have influenced the inter-rater agreement in specific cases. Conclusions. Published radiomic studies provide encouraging but still limited and preliminary data that require further validation to improve the decision-making processes in preventing and managing radiation-induced toxicities

Multiproxy investigation of the last 2,000 years BP marine paleoenvironmental record along the western Spitsbergen margin

A reconstruction of the last 2,000 years BP of environmental and oceanographic changes on the western margin of Spitsbergen was performed using a multidisciplinary approach including the fossil assemblages of diatoms, planktic and benthic foraminifera and calcareous nannofossils and the use of geochemistry (X-ray fluorescence spectroscopy, X-ray diffraction). We identified two warm periods (2,000–1,600 years BP and 1,300–700 years BP) that were associated with the Roman Warm Period and the Medieval Warm Period that alternate with colder oceanic conditions and sea ice coverage occurred during the Dark Ages (1,600–1,300 years BP) and the beginning of the Little Ice Age. During the Medieval Warm Period the occurrence of ice-rafted debris and Aulocoseira spp., a specific diatom genus commonly associated with continental freshwater, suggests significant runoff of meltwaters from local glaciers

Ultrastructural changes in enterocytes in subjects with Hashimoto's thyroiditis

We have recently described1 mucosal ultrastructural impairments, such as height and thickness of microvilli, space between microvilli, and thickness of tight junctions, in non-coeliac type 1 diabetic patients after a preliminary report of an alteration in intestinal mucosal permeability (IP) evaluated by the lactulose/mannitol (LA/MA) test.2,3 Therefore, in the “aetiological” classification of autoimmunity based on initiating factors,4 the category of diet induced diseases could be expanded to include type 1 diabetes and, perhaps, other endocrine autoimmune diseases. Thyroiditis is the most frequently associated autoimmune endocrine disease with type 1 diabetes. Moreover, type 1 diabetes and Hashimoto thyroiditis present similar pathogenetic mechanisms of cellular damage, a cell mediated autoimmunity induced by Th1 cytokines. However, mucosal intestinal morphology and function have not yet been studied in autoimmune thyroiditis patients. Hence we investigated intestinal mucosal ultrastructural morphology and IP in a group of patients with autoimmune thyroiditis. The study was approved by the local ethics committee. Fourteen patients (12 females and 2 males; mean age 33.2 (SD 10.2) years) and 23 controls (12 females and 11 males; mean age 27.9 (SD 8.01) years) were enrolled into the study after giving written informed consent. The diagnosis of autoimmune thyroiditis was based on the following criteria: plasma autoantibody TPO positive at high titre and a typical thyroiditis ultrasound pattern. All patients were in euthyroidism (normal FT3, FT4, and TSH plasma levels without hormonal therapy). Mean duration of known disease was 5.2 (2.5) years. All patients were negative for the presence of antigliadin antibodies IgA and IgG, antiendomysium antibodies IgA, as well as antihuman transglutaminase IgA following a gluten rich Mediterranean diet. Type 1 diabetes mellitus was excluded according to the 1997 American Diabetes Association criteria, and none of the participants had a family history of diabetes mellitus. Other intestinal and endocrine diseases were excluded through clinical and, when indicated, laboratory evaluation. Food or other allergies were excluded. None of the subjects reported gastrointestinal signs or symptoms, or was a habitual smoker, abuser of alcohol, or regularly took non-steroidal anti-inflammatory drugs

Toxicity after moderately hypofractionated versus conventionally fractionated prostate radiotherapy: A systematic review and meta-analysis of the current literature

Background: Moderately hypofractionated radiotherapy (RT) currently represents the standard RT approach for all prostate cancer (PCa) risk categories. We performed a systematic review and meta-analysis of available literature, focusing on acute and late genitourinary (GU) and gastrointestinal (GI) adverse events (AEs) of moderate hypofractionation for localized PCa. Materials and methods: Literature search was performed and two independent reviewers selected the records according to the following Population (P) Intervention (I) Comparator (C) and Outcomes (O) (PICO) question: “In patients affected by localized PCa (P), moderately hypofractionated RT (defined as a treatment schedule providing a single dose per fraction of 3–4.5 Gy) (I) can be considered equivalent to conventionally fractionated RT (C) in terms of G > 2 GI and GU acute and late adverse events (O)?”. Bias assessment was performed using Cochrane Cochrane Collaboration's Tool for Assessing Risk of Bias. Results: Thirteen records were identified and a meta-analysis was performed. Risk of acute GI and GU > 2 adverse events in the moderately hypofractionated arm was increased by 9.8 % (95 %CI 4.8 %–14.7 %; I2 = 57 %) and 1.5 % (95 % CI -1.5 %-4.4 %; I2 = 0%), respectively. Discussion: Overall, majority of trials included in our meta-analysis suggested that moderately hypofractionated RT is equivalent, in terms of GI and GU adverse events, to conventional fractionation. Pooled analysis showed a trend to increased GI toxicity after hypofractionated treatment, but this might be related to dose escalation rather than hypofractionation

Determination of a possible relationship between a single nucleotide polymorphism (SNP) in the promoter region of the <i>SIRT1</i> gene and production and reproduction traits in the Agerolese cattle breed

Sirtuins (sir2-like proteins) belong to the family of class III NAD+-dependent histone deacetylases. Among them, SIRT1 is the most studied sirtuin. It plays a key role in many biological processes in the liver, adipose tissue, muscle, pancreas, testis, ovary and mammary gland. It has an important function in endocrine signaling, with a specific role in glucose and fat metabolism. To date, in bovine species, only few SIRT1 single nucleotide polymorphisms (SNPs) have been reported in the literature. Thus, the aims of the present study were to estimate the allele and genotype frequencies at the g.-274C&thinsp;&gt;&thinsp;G locus in the promoter region of the SIRT1 gene and to investigate, for the first time, the relationship among different genotypes and milk production and some reproduction traits in a sample of cows belonging to the Agerolese breed. All the animals were genotyped at the abovementioned locus using the PCR-RFLP technique. The investigated population was found to be polymorphic at the investigated locus. Concerning milk production performances, significant differences between genotypes were found in daily milk yield (DMY), fat percentage (FC), lactation length (LL), peak daily milk yield (PY) and 305-day milk yield (305MY). Moreover, the effect of the g.-274C&thinsp;&gt;&thinsp;G genotype on age at first calving and calving period was significant. In conclusion, our findings are promising and should encourage scientists to further investigate the effect of genetic polymorphism of sirtuins on milk performance and reproductive traits.</p