Malignancy-Associated Membranous Nephropathy with Positive Anti-PLA2R Autoantibodies: Coincidence or Connection

Membranous nephropathy (MN) is currently classified as either primary – often associated with positive anti-phospholipase-A2 receptor (PLA2R) autoantibodies – or as secondary – associated with malignancy, infection, medications, or autoimmune disease. We present a case of biopsy-proven MN with very high serum titer of anti-PLA2R autoantibodies in a patient with a synchronous diagnosis of poorly differentiated esophageal adenocarcinoma and renal cell carcinoma who presented with nephrotic syndrome. Based on the current classification, MN in the presence of active malignancy is diagnosed as secondary and unlikely to have positive anti-PLA2R autoantibodies. This raises several questions: whether this patient has secondary MN associated with malignancy and coincidentally discovered anti-PLA2R autoantibodies, primary MN due to anti-PLA2R autoantibodies with coincidentally discovered malignancy, or whether malignancy can induce the formation of anti-PLA2R autoantibodies that result in MN. This case report highlights the importance of age-appropriate cancer screening, even in patients with presumed primary MN and positive anti-PLA2R autoantibodies.

Intramuscular vs. Intradermic Needle-Free Vaccination in Piglets: Relevance for Animal Welfare Based on an Aversion Learning Test and Vocalizations

The aim of the present study was to compare intramuscular injection with a needle and intradermic needle-free vaccinations against porcine reproductive and respiratory syndrome (PRRS) in piglets at 28 days old by studying behavioral and physiological reactions. A total of 72 piglets divided into 2 sex-balanced batches were assessed. Within each batch, the piglets were divided into three treatments, which were Hipradermic (0.2 ml of UNISTRAIN® PRRS vaccine administered with an intradermic needle-free device), Intramuscular (IM, 2.0 ml of vaccine), and Control (not vaccinated). Before the vaccination, the piglets were trained to cross a 4-m-long raceway to perform an aversion learning test. The day of vaccination, the time taken to cross the raceway was registered for each piglet at different times: prior to the vaccination and 10 min, 2, 24, 48, and 72 h after the vaccination, to measure variations in these times as signs of aversion to the vaccination process. Vocalizations, as potential signs of pain, were recorded as well at the end of this raceway to analyze their frequency (Hz), duration, and level of pressure (dB) at the moment of vaccination. Salivary cortisol, as a sign of the HPA-axis activity, was assessed 10 min after the vaccination. In addition, activity budgets, local reaction to the vaccine, and serological titer were also considered in the study. Ten minutes after the vaccination, the IM piglets took longer (p < 0.001) to cross the raceway than did the Hipradermic and Control piglets. Vocalizations were significantly different between the three treatments: the Control piglets produced vocalizations with the lowest frequency (p < 0.001) and level of pressure (p < 0.001), and IM with the highest, with Hipradermic in a significant intermediate position (p < 0.001). Accordingly, the day of the vaccination, IM and Hipradermic animals were lying on the side of the vaccine administration a greater proportion of time than were the Control piglets (10, 11, and 6%, respectively; p = 0.027). Salivary cortisol was not significantly different between treatments. The serum titer of antibodies against the PRRS was higher (p < 0.001) in both vaccinated treatments in comparison to the Control piglets. It is concluded that the Hipradermic needle-free vaccination may result in a less aversive experience in piglets than did intramuscular vaccination.

Immunization with Pneumocystis carinii A121–85 antigen activates immune function against P. carinii

Background Pneumocystis pneumonia (PcP), which is caused by Pneumocystis carinii, is a life-threatening infection that affects immunocompromised individuals. Unfortunately, chemoprophylaxis and dapsone are only effective for half of the patients with PcP, indicating that additional preventive methods are needed. We predicated the pneumocystis surface protein A12 sequence 1–85 by DNAStar software and BepiPred, and identified it as a potential vaccine candidate by bioresearch. Methods We used recombinant A121–85 as antigen to immunized mice and detected serum titer of IgG, expression of inflammatory factors by EILSA, qRT-PCR and flow cytometry. Results Our results showed that immunization with recombinant A121–85 increased the serum titer of IgG, promoted the secretion of T lymphocytes, increased the expression of inflammatory factors, and elevated lung inflammatory injury in mice. Conclusions Our findings suggest that A121–85 is a potential vaccine target for preventing Pneumocystis carinii. The evaluation of A121–85-elicited antibodies in the prevention of PcP in humans deserves further investigation.

Design of Alphavirus Virus-Like Particles Presenting Circumsporozoite Junctional Epitopes That Elicit Protection against Malaria

The most advanced malaria vaccine, RTS,S, includes the central repeat and C-terminal domains of the Plasmodium falciparum circumsporozoite protein (PfCSP). We have recently isolated human antibodies that target the junctional region between the N-terminal and repeat domains that are not included in RTS,S. Due to the fact that these antibodies protect against malaria challenge in mice, their epitopes could be effective vaccine targets. Here, we developed immunogens displaying PfCSP junctional epitopes by genetic fusion to either the N-terminus or B domain loop of the E2 protein from chikungunya (CHIK) alphavirus and produced CHIK virus-like particles (CHIK-VLPs). The structural integrity of these junctional-epitope–CHIK-VLP immunogens was confirmed by negative-stain electron microscopy. Immunization of these CHIK-VLP immunogens reduced parasite liver load by up to 95% in a mouse model of malaria infection and elicited better protection than when displayed on keyhole limpet hemocyanin, a commonly used immunogenic carrier. Protection correlated with PfCSP serum titer. Of note, different junctional sequences elicited qualitatively different reactivities to overlapping PfCSP peptides. Overall, these results show that the junctional epitopes of PfCSP can induce protective responses when displayed on CHIK-VLP immunogens and provide a basis for the development of a next generation malaria vaccine to expand the breadth of anti-PfCSP immunity.

Predictors of serological cure after penicillin therapy in HIV-negative patients with early syphilis in Shenzhen, China

Background Syphilis is a common infectious disease worldwide. Serological monitoring is important for syphilis management. We currently know little about the characteristics of this seronegative response. The aim of this study was to explore the factors associated with serological cure after treatment of early syphilis. Methods A retrospective cohort study was conducted and the data of patients with early syphilis in a clinic in Shenzhen from 2011 to 2019 were retrieved. Univariable and multiple Cox proportional hazard regression models were utilized to identify factors associated with a serological cure state among syphilis patients with early syphilis two years after treatment. Results A total of 346 (85.9%) syphilis patients achieved serological cure. The multivariate analysis results revealed that having a baseline TRUST titer >1:8 was associated with an increased probability of serological cure, compared with having a baseline TRUST titer ≤1:8 (HR = 1.43, 95% CI = 1.10–1.85, P<0.01); primary syphilis was positively associated with serological cure, compared with participants with latent early syphilis (HR = 1.72, 95% CI = 1.27–2.33, P<0.001). Conclusions Two years after treatment, a higher percentage of early syphilis patients achieved serological cure. The study indicated that the syphilis stage and baseline serum titer were crucial factors associated with serological cure.

Experiments on obtaining precipitating sera by the Fajiwara method

Experiments on obtaining precipitating sera by the Fajiwara method1).Assistant to T. S. Borodatova.In my first report, published in No. 9 of the Kazan Medical Journal for 1927, I presented the results of immunization of rabbits using a slightly modified method of Dr. Karaganov, and it was noted that the use of the second series of immunization leads to the formation of sera of a higher titer. The highest serum titer obtained in these first experiments was 1: 25000 and the weakest serum had a titer of 1: 2000. I also pointed out there that after primary immunization, it is relatively rare to obtain sera that are suitable in their strength for the purposes of forensic blood testing, and only after the second series of immunization is it possible to obtain such sera.

Post-treatment serological changes in some patients with early syphilis exhibit a parabolic trend

Early syphilis accounts for a large proportion of patients with syphilis. Non- Treponema pallidum tests are commonly used to assess treatment effectiveness by analyzing the serological titer before treatment and six months after treatment. However, serological changes during the first three months after completion of treatment have not been completely understood. This prompted us to investigate whether serum titers of patients exhibit a continuous decrease post-treatment and to assess the trend of change in serological titer during this period. One hundred and seventy-three eligible patients with early syphilis were included in the analysis. Pre-treatment serological titers and those at three and six months post-treatment were compared and analyzed. Serological recovery was defined as a 4-fold or greater decrease in titer from pre-treatment level. Forty patients (23.1%) were found to have an increased serum titer at three months after treatment. Among the 40 patients, 13 patients had primary syphilis, 5 patients had secondary syphilis, and 22 patients had early latent syphilis. The proportion of patients with primary syphilis was higher, and their initial titers were significantly lower. No significant differences were observed with respect to age, gender, or initial treatment. The assessment results of 17 patients (9.8% of the total patients) change. Serological changes in some patients exhibit a parabolic pattern that may affect the clinician’s assessment of patient recovery. Therefore, more frequent assessment of serological titer might be required within the first six months post-treatment.

Cryptococcal Maxillary Osteomyelitis and Osteonecrosis in a 18-Month-Old Dog

An 18-month-old neutered male labradoodle was treated with surgical debridement for maxillary osteomyelitis and sequestrum formation. Histopathologic findings of the necrotic bone were consistent with Cryptococcus subspecies, confirmed with latex agglutination serum titer testing. The patient responded to a combination of fluconazole and surgical debridement and was titer negative after 8 months of medical therapy. The patient never exhibited signs of systemic illness which is commonly reported with cryptococcosis. Cryptococcus subspecies infection in dogs in the Pacific Northwest is part of an ongoing outbreak in the region, first reported in 2001, and is associated with specific risk factors. This is the first published case of oral cryptococcosis from primary inoculation.

In Vitro Preparation And Testing Of Anti-Salmonella Vaccine Against Abortion In Sheep

In March 2016, the microbiology laboratory of the Faculty of Veterinary Medicine in Cluj-Napoca, 3 type of antisalmonella vaccine for sheep were prepared. For type 1, 24 hours salmonella on brain heart infusion (BHI) broth culture, heat inactivated for 1 hour at 60°C, then with formaldehyde in a concentration of 3 ‰. Variant 2 - the culture supernatant obtained on solid BHI medium, washed with PBS, frozen-thawed 6 times, centrifuged at 4000 rpm for 15 minutes, filtered through 0.2 μm Millipore filter Orange Scientific. Variant 3 - suspension of cell walls remaining after centrifugation suspended in PBS and inactivated with formaldehyde.After the bacterial and fungal sterility control, the three types of vaccine were administered in rabbits by the subcutaneous route at a dose of 1 ml/individual along with 1 ml of plant extract adjuvant (decoction of Ewernia prunastri) sterilized by filtration.There have been two booster inoculations of the initial administration, 7 and 14 days after. Before each dose of vaccine, blood was sampled from the marginal auricular vein in order to control the immunogenicity by anti-somatic ˮOˮ serum antibody (Ab) titration using slow microplate agglutination test (Widal reaction). After three inoculations with the vaccine variant 1, Ab serum titer reached 1/128, and in types 2 and 3, 1/512 after 2 inoculations, decreasing to 1/256 after the second booster administered with no immunomodulator.