Gland Infection Research Articles

NanoString evaluation of murine Cytomegalovirus transcription in vivo and in vitro

BackgroundNext Generation Sequencing allows for deep analysis of transcriptional activity in cells and tissues, however it is still a cost intensive method that demands well versed data handling. Reverse transcription quantitative PCR (RT-qPCR) is the most commonly used method to measure gene expression levels, however the information gathered is quite small in comparison to NGS. A newer method called nanoString allows for highly multiplexed gene expression analysis by detecting mRNAs without the use of enzymes for reverse transcription or amplification even for single cells or low input material. The method can be done in 1.5 days and data are quickly analyzed by the accompanied user friendly software.Our aim was to investigate this new method and compare it to the existing alternatives, while investigating murine Cytomegalovirus (mCMV) infection and latency. MethodsmCMV infected murine embryonic fibroblasts (MEF), lung and salivary glands from BALB/c mice were evaluated at different stages of infection. A set of 30 custom designed nanoString probes were tested, 20 probes specific for mCMV genes, 6 probes for host genes known to be influenced by viral infection and 4 reference gene specific probes. nanoString counts were compared to published RNA-Seq RPKM. ResultsWe found that nanoString can be used for analysis of cytomegalovirus gene expression during acute infection in vitro and in vivo, both for virus specific and host genes. Although some transcripts show different expression rates in comparison to NGS data, the most abundant transcripts are comparable. When tissues are infected, there are significantly fewer transcripts than in MEFs, and consistent with previous work there are significant differences in relevant abundance between MEF and tissues. We were unable to detect our viral transcripts of interest in latently infected tissue. ConclusionsFor viruses with annotated transcriptomes, nanoString allows simultaneous quantitation of multiple virus and host genes. One huge advantage of the platform is rapid turnaround and simplicity of analysis. It should prove to be very useful to explore host virus interactions during acute infection, but it is unclear if it has adequate sensitivity for analysis during latency in immunocompetent mice.

FOLFOXIRI/Bevacizumab Plus Nivolumab as First-Line Treatment in Metastatic Colorectal Cancer RAS/BRAF Mutated: Safety Run-In of Phase II NIVACOR Trial.

The NIVACOR trial is a phase II study assessing the efficacy and safety of nivolumab in combination with FOLFOXIRI/bevacizumab in first-line setting in patients affected by metastatic colorectal cancer (mCRC) RAS/BRAF mutated. We report safety run-in results in the first 10 patients enrolled. Patients received triplet chemotherapy with FOLFOXIRI scheme plus bevacizumab, in association with nivolumab every 2 weeks for 8 cycles (induction phase) followed by bevacizumab plus nivolumab every 2 weeks (maintenance phase), until progression of disease or unacceptable toxicities. The first ten patients were evaluated: 7 experienced at least one adverse event (AE) related to FOLFOXIRI/bevacizumab and 2 related to nivolumab. The most frequent grade 1–2 AEs related to FOLFOXIRI/bevacizumab were diarrhea and fatigue (71%), nausea and vomiting (57%); 3 (43%) had grade 3–4 neutropenia, and 2 (20%) patients developed grade 1–2 AEs nivolumab related: skin rash and salivary gland infection. Two patients delayed the dose because of serious AEs, proteinuria and salivary gland infection; one patient discontinued experimental treatment due to the ileo-urethral fistula and concurrent Clostridium infection diarrhea. No treatment- related death occurred. The safety run-in analysis of NIVACOR trial reassured using co-administration of FOLFOXIRI/bevacizumab and nivolumab was well tolerated with an acceptable toxicity profile.Clinical Trial Registration https://clinicaltrials.gov/, (NCT04072198).

A berberine hydrochloride-carboxymethyl chitosan hydrogel protects against Staphylococcus aureus infection in a rat mastitis model

Staphylococcus aureus (S. aureus) is the major pathogen responsible for mastitis in dairy cows, an important threat to their health, but prevention of S. aureus infection of the mammary gland remains challenging. Berberine hydrochloride (BH), a naturally occurring phytochemical, exhibits a wide range of activities, including antibacterial effects on S. aureus. In this study, we prepared a novel berberine hydrochloride-carboxymethyl chitosan hydrogel (BH-CMCH) with excellent thermosensitivity, injectability and in vitro antibacterial activity. In a rat model of mastitis induced by S. aureus, mammary duct injection of BH-CMCH reduced the bacterial load in infected mammary gland tissue and protected the tissue from damage from infection. In addition, proteomics analysis showed that mammary duct injection of BH-CMCH enhanced autolysosome degradation and promoted the innate immune response by activating the lysosomal pathway and up-regulating related significantly differentially expressed proteins (SDEPs). Taken together, the findings support the potential of BH-CMCH as an antibacterial agent against S. aureus-induced mastitis.

Infection of Mammary Glands of Small Mammals in Eastern North America by Helminths.

Simple SummaryFor several decades, it has been known that many species of parasitic worms can infect the mammary glands of their hosts, and that some of these can be transmitted through the mammary glands from mother to nursing young. Such infections have been studied widely in many species of wild and domesticated animals, including livestock as well as cats and dogs, and also in humans. Despite this, field studies specifically designed to determine whether mammary infections occur in wild mammals sampled from their natural environment have not been performed. We explored this by conducting a survey of wild small mammals from natural sites in the states of New York, Tennessee, and Georgia in the eastern United States. We examined 53 wild hosts, including four species of rodents and one shrew, using a new method of removing and mounting whole mammary glands for microscopical study. Many intestinal parasites were found, but worms occurred in the mammary glands of only one species; four cotton rats from Georgia had roundworm larvae in their mammary glands. This is the first general survey of wild mammals to include mammary examination. Based on our positive results, we propose inclusion of mammary examination in all future surveys.To determine whether small mammals living in natural settings harbor helminth infections in their mammary glands, we conducted a survey of helminths infecting rodents and soricimorphs in three widespread locations in the eastern United States: states of New York, Tennessee, and Georgia. We examined all the primary organs in all hosts, and identified all helminths. We also excised the complete mammary glands within their subcutaneous fat pads, then stained and mounted each whole mammary gland set for microscopical examination. A total of 53 individual hosts were examined, including 32 Peromyscus spp., 11 Mus musculus, 5 Sigmodon hispidus, 4 Clethrionomys gapperi, and 1 Blarina carolinensis. Helminths collected included Heligmosomoides sp., Hymenolepis diminuta, Hymenolepis nana, Pterygodermatites peromysci, Schistosomatium douthitti, Syphacia obvelata, Syphacia sigmodontis, and Trichostrongylus sigmodontis. Four S. hispidus were infected by T. sigmodontis in the small intestine; in all four, we also found nematode larvae in lactiferous duct lumen and lactogenic tissue of the mammary glands. We were unable to identify the species of nematode larvae, but the co-occurrence with T. sigmodontis in all cases may suggest an association. Future studies should seek to identify such larvae using molecular and other methods, and to determine the role of these mammary nematode larvae in the life cycle of the identified species. No other host species harbored helminths in the mammary glands. Overall, our results suggest that mammary infections in wild small mammals are not common, but warrant inclusion in future surveys.

Equine Arteritis Virus (EAV) Outbreak in a Show Stallion Population.

(1) Background: Equine arteritis virus (EAV) infection causes reproductive losses and systemic vasculitis in susceptible equidae. The intact male becomes the virus’ reservoir upon EAV infection, as it causes a chronic-persistent infection of the accessory sex glands. Infected semen is the main source of virus transmission. (2) Here, we describe acute EAV infection and spread in a stallion population after introduction of new members to the group. (3) Conclusions: acute clinical signs, acute phase detection of antigen via (PCR) nasal swabs or (EDTA) blood, and seroconversion support the idea of transmission via seminal fluids into the respiratory tract(s) of others. This outbreak highlights EAV’s horizontal transmission via the respiratory tract. This route should be considered in a chronic-persistently infected herd, when seronegative animals are added to the group.

Directed Expression of Tracheal Antimicrobial Peptide as a Treatment for Bovine-Associated Staphylococcus Aureus-Induced Mastitis in Mice.

Bovine mastitis is perplexing the dairy industry since the initiation of intensive dairy farming, which has caused a reduction in the productivity of cows and an escalation in costs. The use of antibiotics causes a series of problems, especially the formation of bacterial antimicrobial resistance. However, there are limited antibiotic-free therapeutic strategies that can effectively relieve bacterial infection of bovine mammary glands. Hence, in this study, we constructed a mammary gland tissue-specific expression vector carrying the antimicrobial peptide of bovine-derived tracheal antimicrobial peptide (TAP) and evaluated it in both primary bovine mammary epithelial cells (pBMECs) and mice. The results showed that the vector driven by the β-lactoglobulin gene (BLG) promoter could efficiently direct the expression of TAP in pBMECs and the mammary gland tissue of mice. In addition, significant antibacterial effects were observed in both in vitro and in vivo experiments when introducing this vector to bovine-associated Staphylococcus aureus-treated pBMECs and mice, respectively. This study demonstrated that the mammary gland tissue-specific expression vector could be used to introduce antimicrobial peptide both in in vitro and in vivo and will provide a new therapeutic strategy in the treatment of bovine mastitis.

SDAV, the Rat Coronavirus-How Much Do We Know about It in the Light of Potential Zoonoses.

Sialodacryoadenitis virus (SDAV) is known to be an etiological agent, causing infections in laboratory rats. Until now, its role has only been considered in studies on respiratory and salivary gland infections. The scant literature data, consisting mainly of papers from the last century, do not sufficiently address the topic of SDAV infections. The ongoing pandemic has demonstrated, once again, the role of the Coronaviridae family as extremely dangerous etiological agents of human zoonoses. The ability of coronaviruses to cross the species barrier and change to hosts commonly found in close proximity to humans highlights the need to characterize SDAV infections. The main host of the infection is the rat, as mentioned above. Rats inhabit large urban agglomerations, carrying a vast epidemic threat. Of the 2277 existing rodent species, 217 are reservoirs for 66 zoonotic diseases caused by viruses, bacteria, fungi, and protozoa. This review provides insight into the current state of knowledge of SDAV characteristics and its likely zoonotic potential.

QUANTIFYING BILATERAL INFECTION PATTERNS IN THE TREMATODE ALLOGLOSSIDIUM RENALE.

Within-host distributions of parasites can have relevance to parasite competition, parasite mating, transmission, and host health. We examined the within-host distribution of the adult trematode Alloglossidium renale infecting the paired antennal glands of grass shrimp. There are 4 possible parasite distributions for infections of paired organs: random, uniform, biased aggregation to 1 particular organ (e.g., left vs. right), or inconsistently biased (aggregated, but does not favor 1 side). Previous work has shown that morphological asymmetries in hosts can lead to biased infections of paired organs. Apparent symmetry between the antennal glands of grass shrimp leads to the prediction that there would be no bias for 1 particular organ. However, an alternative prediction stems from the fact that A. renale is hermaphroditic: aggregation between glands would increase outcrossing opportunities and thus, avoid inbreeding via self-mating. Existing methods to test for an overall pattern did not apply to the A. renale system because of low-intensity infections as well as many 0 values for abundance per unit of the antennal gland. Hence, we used Monte Carlo simulations to determine if the observed overall patterns differed from those expected by randomly allocating parasites into groups of 2. We found that in 3 of 4 data sets, A. renale infections did not deviate from random distributions. The fourth data set had a more uniform pattern than expected by chance. As there was no aggregation between glands and the proportion of worms in single gland infections did not differ from that expected by chance alone, we found no evidence of inbreeding avoidance as might be manifested via a within-host distribution. Given the large proportion of worms in single infections, we predict as a major evolutionary outcome that populations of A. renale will be largely inbred.

Bartholin's gland abscess a rare cause of rectovaginal fistula: A case report and literature review.

IntroductionRectovaginal fistula (RVF) is an abnormal communication between the vagina and the rectum. RVFs caused by Bartholin's gland infection are very rare. We present the case of recurrent rectovaginal fistula complicating a bartholin's gland abcess successfully treated with a Martius flap. The aim of this work is to demonstrate the possibility of complication of bartholin's gland infection by a rectovaginal fistula and the efficacy of Martius flap procedure for recurrent RVF of the low third part of the vagina.ObservationIt is a 30-year-old woman admitted to our department for recurrent RVF due to an abscess of the Bartholin's glands. She was previously treated with a vaginal advancement flap which failed with persistence of the fistula and its symptoms. The patient underwent a RVF repair by Martius flap with complete healing of the fistula.DiscussionRectovaginal fistula is a complex pathology with psycho-social, individual, family, religious and ethno-environmental repercussions. Its main aetiologies are obstetric, rectal surgery. Several techniques including the vaginal or anal advancement flap and the Martius flap are used for the treatment of rectovaginal fistulas. For recurrent fistulas, the Martius flap seems to be the most indicated with better results.ConclusionRectovaginal fistula remain a challenge for surgeons and have major psycho-socio-economic repercussions for the patient. The complication of Bartholin's gland infection by rectovaginal fistula is rare. The Martius flap technique is the method of choice for recurrent rectovaginal fistulas of the lower third of the vagina or in association with other pathologies.

P–082 Effect of semen hyper viscosity (SHV) on blastocyst formation rate and implantation rate

Abstract Study question Does semen hyper viscosity effects blastocyst formation rate Summary answer Hyper viscosity of semen sample later results in poor blastocyst formation rate and lower implantation rate. What is known already Normal range of semen hyper viscosity ranges between 12–29%.Highly viscous semen samples impairs the physical and chemical characteristics of seminal fluid and due to which seminal oxidative damage increases which further increases the ROS and reduces the sperm motility there are some factors that can affect the seminal viscosity out of which one is Male accessory gland infection, Hypo function of prostate seminal vesicles and varicoceles. SHV create hindrance in semen preparation. Study design, size, duration Retrospective study was conducted from June 2019 to Oct 2020 at IVF unit IKDRC hospital. Participants/materials, setting, methods 142 patients were enrolled from June 2019 to Oct 2020 in IVF unit IKDRC hospital and divided into two groups. Group A (n = 83) patients with hyper semen viscosity and Group B (n = 69) patients with normal semen viscosity, inclusion and exclusion criteria’s were same for both the groups, only patient with normozoospermia were taken. Semen analysis was done by using WHO manual 2010. Main results and the role of chance In group A with hyper semen viscosity fertilization rate was (49.2% vs. 70% p = <0.001) vs in group B with normal semen viscosity which is significantly higher in group B, Blastocyst formation rate ( 18.4% vs 35% p = <0.01) and implantation rate (9.4% vs 20% p = <0.005) both are significantly higher in group B . Which implies fertilization rate , blastocyst formation rate and implantation rate is significantly lower in patients with semen hyper viscosity. Limitations, reasons for caution Larger randomized control studies are needed to strengthen these results. Wider implications of the findings: Our study demonstrates that patients having higher semen viscosity have poor blastocyst formation rate and implantation rate due to oxidative stress. Trial registration number Not applicable

SNPs in Mammary Gland Epithelial Cells Unraveling Potential Difference in Milk Production Between Jersey and Kashmiri Cattle Using RNA Sequencing

Deep RNA sequencing experiment was employed to detect putative single nucleotide polymorphisms (SNP) in mammary epithelial cells between two diverse cattle breeds (Jersey and Kashmiri) to understand the variations in the coding regions that reflect differences in milk production traits. The low milk-producing Kashmiri cattle are being replaced by crossbreeding practices with Jersey cattle with the aim of improving milk production. However, crossbred animals are prone to infections and various other diseases resulting in unsustainable milk production. In this study, we tend to identify high-impact SNPs from Jersey and Kashmiri cows (utilizing RNA-Seq data) to delineate key pathways mediating milk production traits in both breeds. A total of 607 (442 SNPs and 169 INDELs) and 684 (464 SNPs and 220 INDELs) high-impact variants were found specific to Jersey and Kashmir cattle, respectively. Based on our results, we conclude that in Jersey cattle, genes with high-impact SNPs were enriched in nucleotide excision repair pathway, ABC transporter, and metabolic pathways like glycerolipid metabolism, pyrimidine metabolism, and amino acid synthesis (glycine, serine, and threonine). Whereas, in Kashmiri cattle, the most enriched pathways include endocytosis pathway, innate immunity pathway, antigen processing pathway, insulin resistance pathway, and signaling pathways like TGF beta and AMPK which could be a possible defense mechanism against mammary gland infections. A varied set of SNPs in both breeds, suggests a clear differentiation at the genomic level; further analysis of high-impact SNPs are required to delineate their effect on these pathways.

Bile Salts Regulate Zinc Uptake and Capsule Synthesis in a Mastitis-Associated Extraintestinal Pathogenic Escherichia coli Strain.

Extraintestinal pathogenic Escherichia coli (ExPEC) strains are major causes of urinary and bloodstream infections. ExPEC reservoirs are not completely understood. Some mastitis-associated E. coli (MAEC) strains carry genes associated with ExPEC virulence, including metal scavenging, immune avoidance, and host attachment functions. In this study, we investigated the role of the high-affinity zinc uptake (znuABC) system in the MAEC strain M12. Elimination of znuABC moderately decreased fitness during mouse mammary gland infections. The ΔznuABC mutant strain exhibited an unexpected growth delay in the presence of bile salts, which was alleviated by the addition of excess zinc. We isolated suppressor mutants with improved growth in bile salts, several of which no longer produced the K96 capsule made by strain M12. The addition of bile salts also reduced capsule production by strain M12 and ExPEC strain CP9, suggesting that capsule synthesis may be detrimental when bile salts are present. To better understand the role of the capsule, we compared the virulence of mastitis strain M12 with that of its unencapsulated ΔkpsCS mutant in two models of ExPEC disease. The wild-type strain successfully colonized mouse bladders and kidneys and was highly virulent in intraperitoneal infections. Conversely, the ΔkpsCS mutant was unable to colonize kidneys and was unable to cause sepsis. These results demonstrate that some MAEC strains may be capable of causing human ExPEC illness. The virulence of strain M12 in these infections is dependent on its capsule. However, capsule may interfere with zinc homeostasis in the presence of bile salts while in the digestive tract.

Histopathological Analysis of Adrenal Glands after Simian Varicella Virus Infection.

Latent varicella zoster virus (VZV) has been detected in human adrenal glands, raising the possibility of virus-induced adrenal damage and dysfunction during primary infection or reactivation. Rare cases of bilateral adrenal hemorrhage and insufficiency associated with VZV reactivation have been reported. Since there is no animal model for VZV infection of adrenal glands, we obtained adrenal glands from two non-human primates (NHPs) that spontaneously developed varicella from primary simian varicella virus (SVV) infection, the NHP VZV homolog. Histological and immunohistochemical analysis revealed SVV antigen and DNA in the adrenal medulla and cortex of both animals. Adrenal glands were observed to have Cowdry A inclusion bodies, cellular necrosis, multiple areas of hemorrhage, and varying amounts of polymorphonuclear cells. No specific association of SVV antigen with βIII-tubulin-positive nerve fibers was found. Overall, we found that SVV can productively infect NHP adrenal glands, and is associated with inflammation, hemorrhage, and cell death. These findings suggest that further studies are warranted to examine the contribution of VZV infection to human adrenal disease. This study also suggests that VZV infection may present itself as acute adrenal dysfunction with “long-hauler” symptoms of fatigue, weakness, myalgias/arthralgias, and hypotension.

Safety and Activity of the Highly Specific BTK Inhibitor BGB-3111 in Combination with the PD-1 Inhibitor BGB-A317 in Patients with B-Cell Lymphoid Malignancies

IntroductionBGB-3111 is a potent, highly specific, and irreversible Bruton tyrosine kinase (BTK) inhibitor, with greater selectivity for BTK vs other TEC- and EGFR-family kinases, and demonstrates favorable pharmacokinetic and pharmacodynamics properties (Tam et al. ASH 2016). BGB-A317, a humanized IgG4 variant monoclonal antibody with no Fc gamma receptor binding, targets the programmed cell death-1 (PD-1) receptor and is being developed for the treatment of solid and hematologic malignancies (Friedlander, ASCO, 2017). The combination of PD-1/PD-L1 inhibitors with B-cell receptor pathway inhibitors is being evaluated in different B-cell malignancies with the expectation of greater benefit for patients. Here, we present early safety data from a Phase 1b trial exploring the combination of BGB-3111 and BGB-A317.MethodsThis is an open-label, multicenter, phase 1b study to evaluate safety, tolerability, and preliminary efficacy of BGB-3111 in combination with BGB-A317 in subjects with B-cell malignancies, including Waldenström's macroglobulinemia (WM), aggressive and indolent non-Hodgkin's lymphoma, and transformed chronic lymphocytic leukemia/follicular lymphoma (FL) amongst other B-cell malignancies. The study includes a standard 3+3 dose escalation phase followed by dose expansion. The dose levels are: Cohort 1, BGB-3111 320 mg once a day (QD) combined with BGB-A317 2.0 mg/kg every 3 weeks (Q3W); Cohort 2, BGB-3111 320 mg QD combined with BGB-A317 5.0 mg/kg Q3W; and Cohort 3, BGB-3111 160 mg BID combined with BGB-A317 200 mg (flat dose) Q3W.ResultsAs of 01 June 2017, 25 pts were enrolled in the dose escalation portion of the trial: 15 pts in Cohort 1 and 10 pts in Cohort 2. Key patient characteristics, safety, and efficacy are shown in the Table.Safety: Median follow - up was 2.8 (range, 0.4-10.7) months. There were no dose-limiting toxicities (DLTs) in Cohort 1. Cohort 2 saw hemolysis in 2 pts, both with WM; one qualified as a DLT. These events were not associated with a positive direct antiglobulin test and resolved with immunosuppressive therapy, but resulted in the decision to exclude further enrollment of WM pts in the trial. No further DLTs were observed after exclusion of WM pts.The most frequent adverse events (AEs) of any cause in Cohort 1 were diarrhea (n=4, 26.7%), fatigue (n=4, 26.7%), and pyrexia (n=3, 20%) and in Cohort 2 were contusion (n=3, 30%), anemia, hemolysis, headache, peripheral edema, thrombocytopenia, and upper respiratory tract infection (n=2, 20% each). Frequent AEs ≥ Grade 3 from both Cohorts included anemia (n=32, 12%), and thrombocytopenia and hemolytic transfusion reaction (n=2, 8% each).Serious AEs related to study treatment were seen in 8 patients: hemolysis (n=2), pneumonitis, infusion-related reaction, abscess limb, pneumonia, anemia, ulcerative keratitis, catheter site hemorrhage, autoimmune encephalitis, dyspnea, and eczema (n=1 each). The encephalitis could not be attributed to other causes and resolved with immunosuppressive therapy. No serious hemorrhages or atrial fibrillation have been reported to date.Discontinuation due to AEs occurred in six patients for the following AEs: hemolysis (n=2), nausea, lymph gland infection, ALT increased and GGT increased (same patient), auto-immune encephalitis, and progression-related complications (n=1 each).Efficacy: Efficacy data is very early with limited follow-up and most pts treated at the lowest dose. So far, 30% of pts have responded, including responses in both WM pts as well as complete responses seen in FL and non-GCB DLBCL pts.ConclusionsThe combination of BGB-3111 and BGB-A317 has a manageable toxicity profile in a wide variety of B-cell malignancies. Autoimmune adverse events, consistent with anti-PD-1 therapy, were observed and managed with supportive care. Notably, hemolysis in 2 WM patients suggestlimitations of this combination in indolent lymphoid diseases such as WM, especially given the risk/ benefit profile of single-agent BGB-3111 in indolent settings .Enrollment is now open for Cohort 3, which will be followed by expansion cohorts to further characterize safety and efficacy of the combination. [Display omitted] DisclosuresCull:Amgen Australia: Other: travel expenses Lugano lymphoma conference 2017; Takeda Australia: Other: travel expenses Highlights of ASH march 2017, Brisbane. Opat:Janssen: Consultancy, Honoraria, Speakers Bureau; Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau; Beigene: Research Funding; Mundipharma: Consultancy; Amgen: Research Funding. Trotman:Janssen Cilag: Other: Funding facilitating research paid to third party (BioGrid Australia), Research Funding. Hilger:BeiGene: Employment. Zhang:BeiGene: Employment. Feng:BeiGene: Employment. Ro:BeiGene: Employment. Huang:BeiGene: Employment. Tam:Abbvie: Honoraria, Research Funding; Janssen Cilag: Honoraria, Research Funding; Roche: Honoraria, Research Funding.

Mechanisms by which mastitis affects reproduction in dairy cow: A review.

Reproductive performance is a key factor in determining the profitability of dairy farm, which is affected by many factors such as environment and diseases. Mastitis is a common and important disease, which has caused huge economic losses to the dairy industries worldwide. Mammary gland infection causes immune responses, resulting in the abnormal secretion of cytokines and hormones and abnormal function of the reproductive system such as the ovary, corpus luteum, uterus and embryo. Cows with mastitis have delayed oestrus, decreased pregnancy rate and increased risk of abortion. The adverse effects of mastitis on reproductive performance are affected by many factors, such as occurrence time, pathogen and cow factors. This paper primarily reviews the progress in the effects and mechanisms of mastitis on reproductive performance, with emphasis on maternal transcriptome, genomic analysis, epigenetic modification, microbiota, inflammatory regulation and immune evasion mechanism of mastitis, aiming to provide directions for the prevention and control of mastitis in the future.

Interventional treatment of Anal Fistula: A Retrospective Analysis

Introduction: Anal fistula is a benign anorectal disease. Infection of Hermann and Desfosses anal glands is responsible for the formation of abscesses and/or fistulas. The main treatment is surgery but recurrence and sometimes incontinence are frequently observed. So to choose surgical methods of anal fistula treatment is very important. Aim: The aim of this retrospective study was to evaluate the reliability and feasibility of Video-assisted anal fistula treatment (VAAFT) at the anal fistula surgery. Materials and Methods: A retrospective analysis was performed on data collected during a 11-year period (2008-2019) from 52 patients who underwent fistulotomy with loose seton technique. The male to female ratio was 3:1 and the mean patient age was 48.34 years. Results: Mortality, recurrence, complications rate were 0%. Though the patients were scheduled as day-surgery cases, the average duration of hospital stay was 1.18 days. Quality of life index (QOLI) for these patients were often be improved by treating their fistula. Conclusion: The appropriate treatment for anal fistula is dependent upon the anatomy and the location of the fistula tract. Detection of the inner mouth is the touchstone in the treatment of anal fistula. It could be determined location of inner mouth of the anal fistula easily with transparent anoscope guideline. VAAFT seems to be a safe and effective technique for treating perianal fistula without recurrence and anal incontinence.

P116 Development of a new patient-reported outcome measure for patients with complex cryptoglandular fistulas

Abstract Background Complex cryptoglandular fistulas (CCF) arise from infected anal glands and are often associated with substantial morbidity and healthcare utilization. Standarized patient-reported outcome measures (PROMs) for CCF are lacking. Thus, we aimed to develop a disease-specific PROM to assess the burden of symptoms and their impact on daily life in patients with CCF. Methods To develop a conceptual model, a targeted literature review was conducted to identify symptoms and impacts on daily life associated with CCF. Existing PROMs relating to anal fistulas were also sought. Semi-structured interviews with colorectal surgeons (n=5) assessed clinical perspectives on patient experience of CCF. A draft item pool was developed based on the refined conceptual model and using the Quality of Life in Patients with Anal Fistula Questionnaire as a reference. The tool was refined through concept elicitation interviews on the symptoms and impacts of CCF, and cognitive debriefing on the interpretation, understanding and response to each item. Interviews were conducted until concept saturation was achieved and patient feedback suggested no further refinements were required. Results The literature review identified discharge, pain, faecal incontinence and bleeding as the most prevalent symptoms, and embarrassment as the most prevalent impact on daily life. Results from surgeon interviews were then used to revise the initial conceptual model. Twenty US adults (60% female; mean age, 49 years) with clinically confirmed CCF participated in interviews (four waves of n=5). Patients identified 10 salient symptoms and 11 salient impacts on daily life (salient defined as mention by ≥50% of patients and mean disturbance rating ≥5 on a 10-point scale). The final conceptual model included the main symptoms and treatment-related effects, and impacts on daily life. The draft item pool was refined, resulting in a final PROM consisting of 14 items (covering frequency and severity) relating to symptom domains – discharge, incontinence, pain, irritation, odour, abscess – and 6 items relating to health-related quality of life domains – functional, physical, psychological, social health. The PROM features a 7-day recall period, with responses mostly given on a 5-point verbal rating scale. Cognitive debriefing confirmed that the PROM was clear, easy to understand and relevant to patients’ experiences. Conclusion The 20-item CCF questionnaire (CCFQ-20) is a new PROM that has been developed and tested for content validity, following expert guidance and regulatory best practices. It addresses a comprehensive set of salient symptoms and impacts experienced by patients with CCF. Psychometric testing is required to fully evaluate this PROM. Sponsor: Takeda Pharmaceuticals USA, Inc.

SARS-CoV-2 Impairs Vision.

Affection of the central nervous system and the eyes is increasingly recognized as manifestations of a SARS-CoV-2 infection (COVID-19). This review aims at summarizing and discussing recent advances concerning causes and locations of impaired vision because of an infection with SARS-CoV-2. On a literature search through PubMed and ScholarOne, all available publications about COVID-19 patients with impaired vision were retrieved. Visual impairment in SARS-CoV-2-infected patients may be due to infection of lacrimal glands (dacryoadenitis), conjunctivitis, tonic pupils, vitritis, central retinal artery/venous occlusion, retinitis, retinal bleeding, panuveitis, anterior ischemic optic neuropathy, optic nerve stroke, optic neuritis, optic perineuritis, or occipital ischemic stroke. Visual impairment may be the initial manifestation of SARS-CoV-2. This mini review shows that impaired vision may be the initial manifestation of COVID-19, that all sections of the visual tract may be affected and causative for visual impairment in COVID-19 patients, and that SARS-CoV-2 manifests along the visual tract with ischemia, focal infection, and immunological reactions.

Cytomegalovirus infection and male infertility: case report

Objectives. To present a case report of male infertility associated with cytomegalovirus infection and the outcome of antiviral treatment.Clinical observation. A 31-year-old man presented with a history of 6 years of infertility. No pathology was revealed in his wife. High loads of cytomegalovirus (CMV) were detected by PCR: in expressed prostatic secretion (EPS) 8700 copies/ml, in ejaculate – 598 440 copies/ml. Sperm examination revealed necrozoospermia and leukospermia. CMV-associated accessory gland infection was verified. The patient was treated with valacyclovir 500 bid for 90 days and interferon α2β suppository (Viferon®) 1 million IU for 30 days. All sperm parameters improved in 1 month after initiation of antiviral treatment. Sperm concentration and motility increased × 1.5 and × 1.4 respectively, sperm viability and leukocyte count achieved reference values. At the same time, CMV loads decreased: EPS to 300 copies/ml, the ejaculate to 54 000 copies/ml. After 3 months (by the end of the antiviral treatment): EPS-negative, the ejaculate – 6060 copies/ml; after 6 months: EPS – negative, the ejaculate 3900 copies/ml. Within 6 months, the woman became pregnant and gave birth to a healthy baby girl. After 3 years, there was a second pregnancy and the birth of a healthy boy.Conclusion. The male factor has been established as the cause of infertility in a married couple; the only probable etiological agent of pathozoospermia was cytomegalovirus infection. The use of complex antiviral and immunotherapy (interferon α2β with antioxidants, Viferon®) provided positive dynamics in clinical, sperm and laboratory parameters, which led to the conception and birth of two children.

Involvement of matrix metalloproteinases and their inhibitors in Staphylococcus aureus chronically infected bovine mammary glands during active involution

The aim of this study was to characterize the protein expression of matrix metalloproteinase-2 (MMP-2) and ‐− 9 and their inhibitors (TIMP-1 and -2) in mammary tissue of dairy cows with naturally occurring chronic S. aureus intramammary infections (IMI) during active involution. Moreover, the gelatinolytic activity of MMP-2 and -9 in mammary secretions was evaluated. Cows in late lactation that were either uninfected or with chronic naturally acquired S. aureus IMI were included in this study. Protein expression of MMP-2 and -9 in mammary tissues was significantly higher in S. aureus-infected than uninfected quarters at day 14 and 21 of involution. Protein expression of TIMP-1 and -2 was significantly higher in S. aureus-infected than uninfected quarters at day 7, 14 and 21 of involution. The MMP-2/TIMP-1, MMP-2/TIMP-2, MMP-9/TIMP-1 and MMP-9/TIMP-2 ratios were significantly higher in S. aureus-infected compared with uninfected quarters at day 14 of involution. The MMP-2 activity was significantly higher in mammary secretions from S. aureus-infected compared with uninfected quarters at day 1, 2, 7 and 14 of involution. The MMP-9 activity was significantly higher in mammary secretions from infected quarters compared with uninfected quarters at day 7, 14 and 21 of involution. The increased expression of MMP-2 and -9 in mammary tissue as well as the high levels of activity observed in mammary secretion from infected quarters compared with uninfected quarters during active involution, strongly suggests that these gelatinases could contribute to degradation of mammary tissue components during chronic S. aureus IMI. The MMPs/TIMPs imbalance could lead to greater proteolysis and potentially more damage to mammary tissue in S. aureus-infected quarters.