Study on Anatomical Structures of the Dromedary Udder.

The objectives of the present study were to describe specific anatomical structures of the dromedary udder. Eighty-six dromedary udders were examined, taking morphological measurements and producing injection casts using resin, gelatin, and paraffin. The udder of the dromedaries consists of four quarters. The shape of the udders and teats varies considerably between animals and is influenced by age, breeding, and lactation status. The most frequently found udder form was the globular udder (48.8%) and the most common teat form in this study was the funnel teat (44.2%). The most common teat tip shape was a smooth or a slightly rough ring teat (61.6%). Injection casts showed a complete separation of the teat canals. There is also no communication between tributary mammary complexes. Resin injections of the glandular tissue adjacent to the teat cistern showed an extensive branching into large, medium, and small milk ducts. Frozen sections of the udder revealed complete separation of the right and left mammary complex through the Sulcus intermammarius. The teat sections showed longitudinal folds from the tip of the teat to the base of the teat. A ring fold at the transition from the Ductus papillaris to the teat cistern was present. The results of this study increase the knowledge of the anatomical structures of the dromedary udder, which may be useful for breeding a selection of dairy dromedaries.

Aging Associates with Cilium Elongation and Dysfunction in Kidney and Pancreas.

Cilia are best known and most studied for their manifold functions enabling proper embryonic development. Loss of cilia or dysfunction thereof results in a great variety of congenital malformations and syndromes. However, there are also cilia-driven conditions, which manifest only later in life, such as polycystic kidney disease. Even degenerative diseases in the central nervous system have recently been linked to alterations in cilia biology. Surprisingly though, there is very little knowledge regarding cilia in normally aged organisms absent any disease. Here, it is provided evidence that cilia in naturally aged mice are considerably elongated in the kidney and pancreas, respectively. Moreover, such altered cilia appear to have become dysfunctional as indicated by changes in cellular signaling.

Role of microRNAs in type 2 diseases and allergen-specific immunotherapy.

MicroRNAs (miRs) have gained scientific attention due to their importance in the pathophysiology of allergic diseases as well as their potential as biomarkers in allergen-specific treatment options. Their function as post-transcriptional regulators, controlling various cellular processes, is of high importance since any single miR can target multiple mRNAs, often within the same signalling pathway. MiRs can alter dysregulated expression of certain cellular responses and contribute to or cause, but in some cases prevent or repress, the development of various diseases. In this review article, we describe current research on the role of specific miRs in regulating immune responses in epithelial cells and specialized immune cells in response to various stimuli, in allergic diseases, and regulation in the therapeutic approach of allergen-specific immunotherapy (AIT). Despite the fact that AIT has been used successfully as a causative treatment option since more than a century, very little is known about the mechanisms of regulation and its connections with microRNAs. In order to fill this gap, this review aims to provide an overview of the current knowledge.

T-cell prolymphocytic leukemia is associated with deregulation of oncogenic microRNAs on transcriptional and epigenetic level.

Deregulation of micro(mi)-RNAs is a common mechanism in tumorigenesis. We investigated the expression of 2083 miRNAs in T-cell prolymphocytic leukemia (T-PLL). Compared to physiologic CD4+ and CD8+ T-cell subsets, 111 miRNAs were differentially expressed in T-PLL. Of these, 33 belonged to miRNA gene clusters linked to cancer. Genomic variants affecting miRNAs were infrequent with the notable exception of copy number aberrations. Remarkably, we found strong upregulation of the miR-200c/-141 cluster in T-PLL to be associated with DNA hypomethylation and active promoter marks. Our findings suggest that copy number aberrations and epigenetic changes could contribute to miRNA deregulation in T-PLL.

Pressure Drives Rapid Burst-Like Coordinated Cellular Motion from 3D Cancer Aggregates.

A key behavior observed during morphogenesis, wound healing, and cancer invasion is that of collective and coordinated cellular motion. Hence, understanding the different aspects of such coordinated migration is fundamental for describing and treating cancer and other pathological defects. In general, individual cells exert forces on their environment in order to move, and collective motion is coordinated by cell-cell adhesion-based forces. However, this notion ignores other mechanisms that encourage cellular movement, such as pressure differences. Here, using model tumors, it is found that increased pressure drove coordinated cellular motion independent of cell-cell adhesion by triggering cell swelling in a soft extracellular matrix (ECM). In the resulting phenotype, a rapid burst-like stream of cervical cancer cells emerged from 3D aggregates embedded in soft collagen matrices (0.5 mg mL-1 ). This fluid-like pushing mechanism, recorded within 8 h after embedding, shows high cell velocities and super-diffusive motion. Because the swelling in this model system critically depends on integrin-mediated cell-ECM adhesions and cellular contractility, the swelling is likely triggered by unsustained mechanotransduction, providing new evidence that pressure-driven effects must be considered to more completely understand the mechanical forces involved in cell and tissue movement as well as invasion.

A retrospective comparison of clinical and radiological outcomes using palmar or dorsal plating to treat complex intraarticular distal radius fractures (AO 2R3 C3).

INTRODUCTION: Complex intraarticular distal radius fractures are common, and treatment with open reduction and internal fixation (ORIF) can be done through either the palmar or dorsal approach. There is scant evidence, however, indicating which approach is more suitable. We compared clinical and radiological outcomes of patients with AO 2R3 C3 fractures surgically treated with one of these approaches. MATERIALS AND METHODS: From January 2015 to November 2018, 72 surgically treated patients with AO 2R3 C3 fractures were radiologically (12 months) and clinically (mean 26 months) evaluated. Forty-one patients underwent ORIF using the palmar approach (Group 1), and the dorsal approach was used in 31 patients (Group 2). Radiological parameters were measured using the AO scoring system immediately following surgery and 12 months later. Clinical assessments included the range of motion, PRWE and DASH scores. RESULTS: At the immediate postoperative assessment, the median AO score was 5.5 (IQR 2-9.5, range 0-30.5) for Group 1 and 8 (IQR 5-15, range 0-27) for Group 2, and 12-month follow-up results were 4.5 (IQR 1.5-10, range 0-41) and 6.5 (IQR 5-11, range 0-29.5), respectively. Group 1 had more favorable results for the flexion, extension, radial abduction, PRWE and DASH parameters. The plate removal and reoperation rates were higher in Group 2. DISCUSSION: When treating complex intraarticular distal radius fractures, we found the palmar approach was more advantageous for this fracture pattern. Nevertheless, a dorsal approach may still be suitable for intraarticular comminuted distal radius fractures with dorsally displaced joint fragments.

Evaluation of vecabrutinib as a model for noncovalent BTK/ITK inhibition for treatment of chronic lymphocytic leukemia.

Covalent Bruton tyrosine kinase (BTK) inhibitors, such as ibrutinib, have proven to be highly beneficial in the treatment of chronic lymphocytic leukemia (CLL). Interestingly, the off-target inhibition of IL-2-inducible T-cell kinase (ITK) by ibrutinib may also play a role in modulating the tumor microenvironment, potentially enhancing the treatment benefit. However, resistance to covalently binding BTK inhibitors can develop as the result of a mutation in cysteine 481 of BTK (C481S), which prevents irreversible binding of the drugs. In the present study we performed preclinical characterization of vecabrutinib, a next-generation noncovalent BTK inhibitor that has ITK-inhibitory properties similar to those of ibrutinib. Unlike ibrutinib and other covalent BTK inhibitors, vecabrutinib showed retention of the inhibitory effect on C481S BTK mutants in vitro, similar to that of wild-type BTK. In the murine Eµ-TCL1 adoptive transfer model, vecabrutinib reduced tumor burden and significantly improved survival. Vecabrutinib treatment led to a decrease in CD8+ effector and memory T-cell populations, whereas the naive populations were increased. Of importance, vecabrutinib treatment significantly reduced the frequency of regulatory CD4+ T cells in vivo. Unlike ibrutinib, vecabrutinib treatment showed minimal adverse impact on the activation and proliferation of isolated T cells. Lastly, combination treatment with vecabrutinib and venetoclax augmented treatment efficacy, significantly improved survival, and led to favorable reprogramming of the microenvironment in the murine Eµ-TCL1 model. Thus, noncovalent BTK/ITK inhibitors, such as vecabrutinib, may be efficacious in C481S BTK mutant CLL while preserving the T-cell immunomodulatory function of ibrutinib.

Using mini-arthrotomy for dorsal plating to treat intraarticular distal radius fractures: can it improve radiological and clinical outcomes?

PURPOSE: Using palmar plating to treat complex intraarticular distal radius fractures is standard of care. However, fracture fragments can also be managed using a dorsal approach with arthrotomy, which is useful when treating fractures involving the dorsal joint aspect. We compared radiological and clinical outcomes after dorsal plating with or without an intraoperative arthrotomy. METHODS: 31 of the 359 patients with a distal radius fracture had an AO Type 2R3 C3 fracture surgically treated using a dorsal approach (01/2015-10/2018). Fractures other than C3 were excluded from this analysis. Group 1 (n = 14) had no arthrotomy, Group 2 (n = 17) underwent intraoperative dorsal mini-arthrotomy. Clinical results were measured by range of motion (ROM), Patient-rated wrist evaluation (PRWE) and Disabilities of arm, shoulder and hand (DASH) scores. Radiological results were evaluated using the AO scoring system. RESULTS: ROM, DASH and PRWE did not differ significantly between groups. Joint surface restoration was insufficient in five patients in Group 1 (p = 0.05). A trend towards better radiological results, although not statistically significant, was noted in Group 2 (p = 0.06). Plate removal was performed in 12 patients due to limited ROM (6 patients in each group). One patient (Group 2) with chronic pain and step off in the joint line underwent corrective osteotomy. CONCLUSIONS: We did not detect a difference in patient outcomes using the dorsal longitudinal mini-arthrotomy; however, it may prevent incongruent joint reconstruction since all cases occurred in Group 1. In the absence of intraoperative CT scan, longitudinal mini-arthrotomy may be used to enhance visualization and achieve joint surface reconstruction.

Evaluation of the clinical efficacy of a water soluble formulation of tylvalosin in the control of enzootic pneumonia associated with Mycoplasma hyopneumoniae and Pasteurella multocida in pigs.

BACKGROUND: The efficacy of a water soluble formulation of tylvalosin (Aivlosin® 625 mg/g granules) was evaluated in the treatment and metaphylaxis of Enzootic Pneumonia (EP) in pigs. In all four trials, pigs in the tylvalosin group were administered 10 mg tylvalosin/kg bodyweight in drinking water daily for 5 consecutive days (TVN). In a single-challenge study, pigs were inoculated with lung homogenate containing Mycoplasma hyopneumoniae. In a dual challenge study, pigs were sequentially inoculated with pure culture of M. hyopneumoniae and Pasteurella multocida. Efficacy was evaluated based on reduction of lung lesions compared to unmedicated control pigs (CTL). In two field studies at European commercial farms with confirmed outbreaks of EP, treatment efficacy in clinically affected fatteners was evaluated based on improved clinical conditions compared to pigs treated with tylosin at 10 mg/kg by injection for 3 consecutive days (TYL). In these field trials, healthy in contact pigs were enrolled for metaphylaxis efficacy evaluation based on reduction in incidence of new clinical cases of respiratory disease compared to unmedicated pigs (CTL). RESULTS: In the M. hyopneumoniae-only challenge study, pigs in TVN group had lower lung lesion scores than CTL (6.52 vs. 14.97; p <  0.001). In the dual challenge study with M. hyopneumoniae and P. multocida, pigs in TVN group had lower lung lesion scores than CTL (3.32 vs. 8.37; p <  0.01) and the recovery of both challenge bacteria from the lungs was lower in TVN compared with CTL group (p <  0.01). In field outbreaks of EP, multicentre analysis showed that 13 days after the start of medication, treatment success for TVN pigs was significantly better than for TYL pigs (80.0% vs 48.7% p = 0.03) and metaphylactic administration of TVN significantly reduced the incidence of new clinical cases (2.1% vs. 7.8%; p <  0.01) compared with unmedicated controls. CONCLUSIONS: Tylvalosin at 10 mg/kg daily for 5 days in drinking water was safe and effective in the treatment and metaphylaxis of EP in pigs associated with infections of M. hyopneumoniae either alone or in combination with P. multocida under both experimental challenge and field natural infection conditions.

Primary bone lymphoma: Clinical presentation and therapeutic considerations.

BACKGROUND: Primary lymphoma of bone (PBL) is a rare entity. Due to unspecific clinical signs and equivocal radiographs diagnosis may be delayed. This retrospective report of 109 PBL cases demonstrates typical aspects of the lesion. Treatment and prognostic factors are evaluated. METHODS: Retrospectively patient records were reviewed. All patients were followed for evidence of local or distant recurrence. Overall survival (OS) was used as clinical outcome. RESULTS: The median age of the 109 patients was 62.8 years. The most common symptoms were pain (76%), swelling (29%), neurologic symptoms and pathological fracture (16% each). Mean duration of symptoms was 8 months (0-197 months).19% of patients had indolent NHL subtypes, 72% aggressive NHL subtypes and 7% cases Hodgkin disease. Cyclophosphamid, doxorubicin, vincristine and prednisone (CHOP) or CHOP plus rituximab (RCHOP) were given in 88 (81%) of patients. Radiotherapy was delivered in 67 (61%) of cases. 51 (47%) patients received both. Surgical interventions were restricted to cases with complications as fractures.The 5-year OS was 66%. The 5-year OS was 66%. In the subgroup of 78 patients with aggressive NHL subtype there was a highly significant benefit for chemotherapy or chemotherapy and radiation in comparison to no treatment or radiation alone. Raised LDH, age, IPI and ECOG performance were prognostic factors. In multivariate analysis, age and raised LDH levels only kept significance. CONCLUSIONS: In our series of primary bone lymphoma, chemotherapy resulted in a better outcome than Radiotherapy alone. Long-term survival is based on the stage of the disease, favoring younger (<60 years) patients with solitary bone lesions, low level of LDH and favourable ECOG performance status and IPI scores.

[Resection of soft tissue tumours : Pitfalls, typical complications and prevention strategies]. / Weichteiltumorresektionen : Fallstricke, typische Komplikationen und Vermeidungsstrategien.

Benign soft tissue lesions are 300 times as common as soft tissue sarcomas; hence, the likelihood of confusion is high. Lesions that are larger than 5 cm, deep, show infiltrative growth, or recur despite benign histology are suspicious for soft tissue sarcoma. The biopsy incision must be carefully chosen; in large lipomas, atypical lipomatous tumor should be considered in the differential diagnosis. Lymphomas can be misdiagnosed and treated as undifferentiated soft tissue sarcoma. Vascular tumors and epithelioid lesions require more attention in histopathologic diagnostics and staging. Inflammatory lesions and aggressive fibromatosis (desmoid tumor) should also be borne in mind. In general, staging should be adapted to the underlying tumor biology. Neoadjuvant and adjuvant multimodal therapy must be discussed with the patient and used in a targeted manner. Superficial infiltrating sarcomas are prone to intralesional resection and may require intraoperative frozen section histology. If plastic reconstruction is necessary, a two-step procedure after proven tumor-free margins can be beneficial. Cavities and seromas, tight sutures, and closing the wound with clips are particularly critical. Wound drains at the thigh, pelvis, and groin should be left longer. Early revision in cases of hematoma or critical wound healing have proven beneficial. Adjuvant therapies are best planned before discharge from hospital. Overall, tumor-specific follow-up can significantly reduce the disadvantages of a recurrence resection.

Efficacy of an orally administered anti-diarrheal probiotic paste (Pro-Kolin Advanced) in dogs with acute diarrhea: A randomized, placebo-controlled, double-blinded clinical study.

BACKGROUND: Acute diarrhea is a common clinical presentation of dogs. The effect of specific anti-diarrheal probiotic pastes (ADPPs) in the management of acute, uncomplicated diarrhea in dogs is unknown. HYPOTHESIS: Administration of an ADPP containing Enterococcus faecium 4b1707 will improve the clinical outcome of acute, uncomplicated diarrhea in dogs compared to placebo. ANIMALS: One hundred forty-eight client-owned dogs with acute diarrhea as the main clinical sign. METHODS: Double-blinded, placebo-controlled, randomized, blocked, multicenter clinical field study conducted at 14 primary care veterinary practices in the United Kingdom and Ireland. RESULTS: The ADPP was associated with better clinical outcome compared to placebo in dogs with acute, uncomplicated diarrhea. Dogs in the ADPP group had a significantly shorter duration of diarrhea (ADPP: median, 32 hours; 95% confidence interval [CI], 2-118; n = 51; Placebo: median, 47 hours; 95% CI, 4-167; n = 58; P = .008) and the rate of resolution of diarrhea was 1.60 times faster in the ADPP group than in the Placebo group (ratio, 1.60; 95% CI, 1.08-2.44; P = .02). Fewer dogs required additional medical intervention (AMI) for non-improvement or worsening in the ADPP group compared to the Placebo group (3.5% of dogs and 14.8% of dogs, respectively), with a relative risk of 0.88 (P = .04; AMI, ADPP, 3.5%, 2/57 dogs; Placebo, 14.8%, 9/61 dogs; relative risk, 0.88; 95% CI, 0.77-0.99). CONCLUSION AND CLINICAL IMPORTANCE: The ADPP may accelerate resolution of acute diarrhea in dogs and decrease the requirement for AMI.