Moderate Signs Research Articles

Recombination and Pathogenicity Analysis of NADC30-like and QYYZ-like PRRSV Strains in South China.

Since 2010, the Lineage 1 (NADC30-like) and Lineage 3 (QYYZ-like) strains of PRRSV-2 have become widespread in China, undergoing recombination and resulting in varying virulent and immune-evading mutants that have severely impacted the pig farming industry. In this study, we isolated one NADC30-like strain (GXHX20211106) and one QYYZ-like strain (GXGG202007) from pig serum samples collected in southern China. Comparative genomic analysis revealed that GXHX20211106 shares 90% identity with NADC30, while GXGG202007 shows 91.4% similarity to QYYZ. Both strains exhibit characteristic amino acids deletions or insertions in the Nsp2 region. Phylogenetic analyses further classified GXHX20211106 within Lineage 1.8 (NADC30-like) and GXGG202007 in Lineage 3 (QYYZ-like). Recombination analysis demonstrated that GXHX20211106 resulted from recombination between NADC30-like and HP-PRRSV-like strains, while GXGG202007 originated from recombination events involving QYYZ-like, VR-2332-like, and HP-PRRSV-like strains. Pathogenicity studies in piglets indicated that both isolates caused moderate clinical signs, with GXHX20211106 showing higher virulence compared to GXGG202007. No deaths were recorded in the infected piglets. These findings highlight the critical role of recombination in shaping PRRSV virulence and underscore the need for ongoing surveillance and control measures to mitigate the impact of recombinant PRRSV strains in southern China.

Asymptomatic and oligosymptomatic states of dysferlinopathy

Dysferlinopathy is a phenotypically heterogeneous, inherited, progressive muscular dystrophy caused by mutations in the DYSF gene. Dysferlinopathy is marked by elevated serum creatine kinase (CK) and can in some cases manifest as hyperCKemia in asymptomatic or low-symptom states. Here, we describe the clinical signs and symptoms and laboratory and imaging results with quantitative MRI analysis of eight pediatric patients at asymptomatic and oligosymptomatic states of dysferlinopathy (aged 3–14 years). Seven of them with a same homozygous mutation and one with a compound heterozygous mutation in the DYSF gene. Based on this case series, we propose two stages of dysferlinopathy disease progression. The first state is asymptomatic hyperCKemia laboratory syndrome of myocytolysis, which is marked by an increase in CK (>1.5 times the upper limit of normal (ULN)) and lactic dehydrogenase (LDH). Second state (oligosymptomatic): increasing CK (2.7–12.6 × ULN), LDH, alanine aminotransferase (ALT), and myoglobin; minimal or moderate signs of fatty muscle infiltration, displacement of the center of support to the back of the foot during plantography; slight afterload fatigue of the calf muscles; slight decrease in muscle strength (imperceptible to the patient) and decrease in Achilles reflexes. Taken together, isolated hyperCKemia (asymptomatic stage) and oligosymptomatic patients form a single continuum of pre-manifest cases.

Standardization and Evaluation of the LAMP Technique for the Diagnosis of Canine Visceral Leishmaniasis in Conjunctival Swab Samples Using DNA Extracted by a Silica Column and Boiling.

The diagnosis of canine visceral leishmaniasis (CVL) presents a challenge due to a variety of non-specific clinical signs. The available tests have low sensitivity. This study aimed to standardize and evaluate the loop-mediated isothermal amplification technique with K26 target (K26-LAMP) for diagnosis of CVL in conjunctival swab (CS) DNA samples extracted through a silica column commercial kit (SW-kit) and boiling (SW-DB) and to compare sensitivity with conventional PCR (kDNA-cPCR) and quantitative real-time PCR (18S-qPCR). Clinical samples of CSs were collected from 54 dogs after reactive serology tests. Positive parasitological and/or histological tests were used as inclusion criteria for a sensitivity analysis. A total of 79.2% (43/54) of dogs without clinical signs or with mild, moderate, or severe clinical signs were included in the study. The sensitivity results of K26-LAMP, kDNA-cPCR, and 18S-qPCR were 72.1%, 81.4%, and 80.5% with the SW-kit and 97.2%, 95.2%, and 57.1% with SW-DB, respectively. In all techniques, the proportion of positives was higher in the group with severe clinical disease, with statistically significant differences in the K26-LAMP and 18S-qPCR techniques being seen with the SW-kit. The results obtained with LAMP for CS samples are promising and its performance is similar to other techniques.

Effects of Intense Pulsed Light on Presumed Neuropathic Pain Associated with Meibomian Gland Dysfunction: A Before-After Study.

Purpose: Meibomian gland dysfunction (MGD) may cause chronic ocular surface pain (COSP) with a neuropathic component that can significantly impact quality of life and be poorly responsive to conventional treatments of MGD. Intense pulsed light (IPL) is an emerging treatment already acknowledged as improving refractory MGD, potentially modulating inflammatory mediators on the ocular surface. This study aimed to assess the impact of IPL on COSP associated with unresponsive MGD. Methods: A monocentric prospective study has been conducted from 2021 to 2023 on patients presenting with moderate MGD and COSP non-responsive to conventional treatments of MGD. Neuropathic pain components were suspected when severe discomfort (OSDI score above 33/100) was observed despite moderate objective signs. Three sessions of IPL were performed at a two-week interval. The primary outcome was change in OSDI at day 60. Secondary outcomes included OSDI modification at D120, DEQ-5, and Pentascore results at D60/D120, together with changes in clinical [Schirmer I, Fluorescein Break-up time (BUT), fluorescein staining, and MGD classification] and paraclinical tests [noninvasive BUT, tear meniscus height (TMH), and meibography]. Results: A significant improvement of COSP (p < 0.05 for changes in OSDI and Pentascore results) was observed 2 and 4 months after the last IPL session, together with an improvement in tear film stability, corneal epitheliopathy, meibomian gland obstruction, and TMH. Conclusion: The results of this study suggest the beneficial effect of IPL on neuropathic component of COSP associated with MGD. The underlying mechanisms involved in that improvement, presumably related to downgrading of inflammatory effectors, remain however to be explored.

Dynamical Evolution of Four Old Galactic Open Clusters Traced by Their Constituent Stars with Gaia DR3

We investigate the evolutionary stages of four open clusters—Berkeley 39, Collinder 261, NGC 6819, and NGC 7789—of ages ranging from 1.6 to 6 Gyr. These clusters have previously been classified into dynamically young and intermediate age groups based on the segregation level of BSS with respect to red-giant-branch stars and main-sequence stars, respectively. We identify members of these four clusters using the ML-MOC algorithm on Gaia DR3 data. To examine the relative segregation of cluster members of different evolutionary stages, we utilize cumulative radial distributions, proper motion distributions, and spatial distributions in galactocentric coordinates. Our analysis shows that Berkeley 39 and NGC 6819 exhibit moderate signs of population-wise segregation from evolved to less-evolved members. NGC 7789 shows signs of mass segregation only in the cumulative radial distributions. On the other hand, Collinder 261 exhibits high segregation of BSS in the cumulative radial distribution, while other populations show the same level of segregation.

Novel in vivo TDP-43 stress reporter models to accelerate drug development in ALS.

The development of therapies to combat neurodegenerative diseases is widely recognized as a research priority. Despite recent advances in understanding their molecular basis, there is a lack of suitable early biomarkers to test selected compounds and accelerate their translation to clinical trials. We have investigated the utility of in vivo reporters of cytoprotective pathways (e.g. NRF2, p53) as surrogate early biomarkers of the ALS degenerative disease progression. We hypothesized that cellular stress observed in a model of ALS may precede overt cellular damage and could activate our cytoprotective pathway reporters. To test this hypothesis, we generated novel ALS-reporter mice by crossing the hTDP-43tg model into our oxidative stress/inflammation (Hmox1; NRF2 pathway) and DNA damage (p21; p53 pathway) stress reporter models. Histological analysis of reporter expression in a homozygous hTDP-43tg background demonstrated a time-dependent and tissue-specific activation of the reporters in tissues directly associated with ALS, before moderate clinical signs are observed. Further work is warranted to determine the specific mechanisms by which TDP-43 accumulation leads to reporter activation and whether therapeutic intervention modulates reporters' expression. We anticipate the reporter strategy could be of great value in developing treatments for a range of degenerative disorders.

Interleukin-6 as a Prognostic Factor of Severity in SARS-CoV-2 Infected Egyptian Patients

Abstract Background Coronavirus disease 2019 (COVID-19) was announced in early December 2019. The pandemic situation is declared. Patients diagnosed as severe or critical cases are prone to multiple organ dysfunction syndrome, acute respiratory distress syndrome and even death This study aimed to evaluate the role of biomarkers in estimating the severity and predicting the prognosis of COVID-19. Objectives This cohort retrospective and prospective analysis were carried out to evaluate the association between IL-6 and severe disease and mortality in COVID-19 disease. Patients and Methods An analytical cohort retrospective and prospective study, it was performed in Fever Military Hospital-Almaza-Cairo-Egypt in period between 1/11/2020 till 1/11/2021 including all confirmed cases presented by moderate or severe symptoms and signs of covid19 manifestations. Results 227 patients were included in this study, 72% of them were males and the mean age was 61years old. About 37% of patients needed ICU admission and 46% of all patients died. The median level of IL-6 after 5 days of admission time in patients who still alive was 290.2 while more than level in died patients was 415. In patients who had extra- pulmonary manifestations we found that the median level of IL-6 after 5 days of admission time was 405.5 while in patients without extra-pulmonary manifestations was 242.45 with significant association. The median level of IL-6 after 5 days of admission time in patients who needed ICU admission was 300.4 while in patients didn’t need ICU was 408.8 without significant association. Conclusion This study revealed that elevated IL-6 is significantly related to prolongation of hospital stay in COVID-19 patients and Severity of disease. Also, the occurrence of death among patients who had increased IL-6 in the time of admission was higher than patients with normal or lower serum levels of IL-6. There was a significant relation between elevated IL-6 and extrapulmonary manifestations.

An empirical study of the post-experiential growth of military personnel – combatants

The need to find innovative technologies for psychological recovery and rehabilitation of servicemen – combatants, taking into account the positive personal changes that can develop as a result of their experience of traumatic and non-traumatic (negative stressful) events in a combat situation, led to the choice of the research topic. The purpose of the study is to examine the relationship between the post-experiential growth of servicemen and women combatants and their life and combat experience. The study was conducted in the period from January 2023 to January 2024 among 375 servicemen and servicewomen of the Armed Forces of Ukraine. The study used theoretical (analysis, synthesis, systematisation, generalisation of information) and diagnostic (S. Blight and K. Norris Post-Experiential Growth Questionnaire; Combat Exposure Scale; author's questionnaire consisting of 5 questions to determine the presence of traumatic events in life and in the workplace). The empirical study has established that: 1) moderate signs of positive psychological changes were found in groups of military personnel both with and without traumatic experience; 2) no statistically significant differences were found between the level of manifestation of signs of post-experiential growth in groups of military personnel with and without traumatic experience, while the size of the standardised effect was insignificant; 3) signs of post-experiential growth in servicemen and women who participated in combat operations have positive correlations with the rates of injury and the presence of a serious event in their life and combat experience. The results of the study give grounds to identify and build on positive psychological changes in a wider range of servicemen and women and veterans as a personal resource in the course of their psychological recovery and psychological rehabilitation. Positive psychological changes are moderately manifested in groups of military personnel – combatants with different life and combat experience. At the same time, there were no statistically significant differences between the manifestation of post-experiential growth in servicemen and women combatants of these groups. This confirms the idea that post-experiential growth of servicemen and women combatants can occur, unlike post-traumatic growth, as a result of experiencing not only traumatic but also non-traumatic (negative stressful) events.

A New Methodology for the Oxygen Measurement in Lung Tissue of an Aged Ferret Model Proves Hypoxia during COVID-19.

Oxygen as a key element has a high impact on cellular processes. Infection with a pathogen such as SARS-CoV-2 and after inflammation may lead to hypoxic conditions in tissue that impact cellular responses. To develop optimized translational invitro models for a better understanding of physiologic and pathophysiologic oxygen conditions, it is a prerequisite to determine oxygen concentrations generated invivo. Our study objective was the establishment of an invasive method for oxygen measurements using a luminescence-based microsensor to determine the dissolved oxygen in the lung tissue of ferrets as animal models for SARS-CoV-2 research. By way of analogy to humans, aged ferrets are more likely to show clinical signs after SARS-CoV-2 infection than are young animals. To investigate oxygen concentrations during a respiratory viral infection, we intratracheally infected nine aged (3-yr-old) ferrets with SARS-CoV-2. The aged SARS-CoV-2-infected ferrets showed mild to moderate clinical signs associated with prolonged viral RNA shedding until 14 days postinfection. SARS-CoV-2-infected ferrets showed histopathologic lung lesion scores that significantly negatively correlated with oxygen concentrations in lung tissue. At 4 days postinfection, oxygen concentrations in lung tissue were significantly lower (mean percentage O2, 3.89 ≙ ≈ 27.78 mm Hg) than in the negative control group (mean percentage O2, 8.65 ≙ ≈ 61.4 mm Hg). In summary, we succeeded in determining the pathophysiologic oxygen conditions in the lung tissue of aged SARS-CoV-2-infected ferrets.

Living a private lie: intersectional stigma, depression and suicidal thoughts for selected young key populations living with HIV in Zambia

BackgroundLimited research has been conducted on the forms, manifestations and effects of intersectional stigma among young HIV-positive men who have sex with men (MSM) and transgender women (TGW) in Zambia. In this study, we aimed to address this gap by elucidating the experiences of these in a small group of young, HIV + MSM and TGW in Zambia.MethodsWe applied a mixed-methods design. Data were collected from January 2022 to May 2022. Qualitative data were collected using in-depth interviews while quantitative data were collected using a questionnaire. Qualitative transcripts were coded using thematic analysis while paper-based questionnaire data were entered into Kobo Connect. Descriptive statistics, using chi-squared tests were calculated using Excel. In this paper, we provide a descriptive profile of the sample and then focus on the qualitative findings on intersectional stigma, depression, and contemplation of suicide.ResultsWe recruited 56 participants from three sites: Lusaka, Chipata, and Solwezi districts. Participants’ mean age was 23 years. The study found that 36% of all participants had moderate to significant symptoms of depression, 7% had major depression, 30% had moderate signs of anxiety, 11% had high signs of anxiety, 4% had very high signs of anxiety and 36% had contemplated suicide at least once. A greater proportion of TGW had moderate to significant symptoms of depression (40%) or major depression (10%) compared to MSM, at 33% and 6%, respectively (X2 = 0.65; p = 0.42). Similarly, more TGW (55%) had contemplated suicide than MSM peers (36%, X2=1.87; p = 0.17). In the qualitative data, four emergent themes about the forms, manifestations, and effects of intersectional stigma were (1) HIV, sexual orientation, and gender identity disclosure; (2) Dual identity; (3) Challenges of finding and maintaining sexual partners; (4) Coping and resilience. Overall, having to hide both one’s sexuality and HIV status had a compounding effect and was described as living “a private lie.”ConclusionEffectively addressing stigmas and poor mental health outcomes among young HIV-positive MSM and TGW will require adopting a socio-ecological approach that focuses on structural interventions, more trauma-informed and identity-supportive care for young people with HIV, as well as strengthening of authentic community-informed public health efforts.

SARS-CoV-2 morbidity, treatment interventions, and vaccination practices in tigers (Panthera tigris ssp) in North American zoos.

Evaluate SARS-CoV-2 morbidity, mortality, clinical signs, treatment interventions, and vaccination practices in tigers under professional care. Amur (Panthera tigris altaica), Sumatran (Panthera tigris sumatrae), and Malayan (Panthera tigris jacksoni) tigers managed under the Tiger Species Survival Plan (SSP). A retrospective, voluntary online survey was sent to all North American zoos holding SSP tigers between January 2020 and June 2023. Responses were received from 55 of 108 institutions (51%) housing 162 tigers in total, and SARS-CoV-2 infection was diagnosed in 39 tigers from 15 institutions (20 Amur, 8 Sumatran, and 11 Malayan [1 to 18 years old; 17 males and 22 females]). This corresponds to a minimum study group infection incidence of 24% over 42 months. Clinical signs included dry cough (82%), inappetence (64%), lethargy (62%), nasal discharge (46%), wheezing (31%), wet cough (18%), and ocular discharge (15%). Most cases were characterized as mild (n = 22) or moderate (14). A single case was characterized as severe. Two cases were asymptomatic. Seventeen positive tigers had been vaccinated once (n = 8) or twice (9) for SARS-CoV-2 prior to infection. No deaths due to SARS-CoV-2 were reported in the study group. Treatment interventions included antibiotics (49%), NSAIDs (18%), antiemetics (15%), and fluids (13%). No treatments were administered in 19 of 39 cases (49%). Amongst participating institutions, 69% reported fully vaccinating tigers for SARS-CoV-2 (≥ 2 doses). Most SARS-CoV-2-infected tigers presented with mild to moderate clinical signs and recovered with limited to no treatment interventions. Asymptomatic SARS-CoV-2 infections can occur in tigers and may be underreported. Tigers vaccinated for SARS-CoV-2 remain susceptible to infection.

The hybrid humerus reverse shoulder arthroplasty: a prospective study of bone grafting and metaphyseal fixation with undersized stem in the assessment of proximal humeral stress shielding and associated clinical outcome

BackgroundA significant proportion of revisions after reverse shoulder arthroplasty (RSA) is attributed to the humeral component. The purpose of this study is to evaluate the radiographic and clinical outcomes of the hybrid humerus technique for RSA using a Grammont-style humeral prosthesis in an onlay fashion with metaphyseal bone impaction grafting technique and undersized stem to avoid humeral stress shielding, notching, and loosening. MethodsThis is a prospective case series of patients who underwent RSA using the hybrid humerus technique with a minimum 2-year follow-up. Key steps of this technique include the use of undersized Grammont-style stem, impaction bone grafting of the proximal 5 cm of the humerus, and adjusting the height and offset of the stem depending on the patient stature, desired lateralization and distalization, and joint and soft tissue tension. Radiographic assessments were performed immediately after surgery, and at 1 and 2 years after surgery. These included assessment of metaphyseal and diaphyseal filling ratio, cortical narrowing, radiolucent lines, cortical lucencies, spot welding, scapular notching, and stem alignment. Preoperative and 2-year postoperative clinical assessments included American Shoulder and Elbow Surgeons score, Constant-Murley Score, University of California Los Angeles score, visual analog scale for pain, and active range of motion. Correlation between the filling ratios and clinical outcomes were also evaluated. ResultsSixty-one patients were included in the study. The average metaphyseal and diaphyseal filling ratio on the postoperative X-ray was 0.66 and 0.54, and 0.67 and 0.54 at 2 years, respectively. Stress shielding was graded as none in 24 (40.7%), mild in 33 (55.9%), and moderate in 2 (3.4%). No stem had a change in position of more than 5°. At 2 years of follow-up, no humeral implant loosening was noted, with only 2 (3.4%) of the stems at risk of loosening. Thirty-nine (66.1%) had no notching, 14 (23.7%) were graded as mild, and 6 (10.2%) had moderate signs of notching. All clinical assessments significantly improved at 2 years (P < .001), with a weak negative correlation between visual analog scale and metaphyseal filling ratio (r = −0.268, P = .036) but none between diaphyseal filling ratio and clinical outcomes. ConclusionThe hybrid humerus technique of metaphyseal bone grafting with a low filling ratio stem presents a promising solution for reducing humeral complications in RSA. This technique demonstrates a low incidence of stress shielding and loosening, with excellent clinical outcomes at 2 years.

Assessment of volume status of pediatric hemodialysis patients.

Accurate volume status assessment and dry weight achievement are the most challenging goals for a nephrologist. We aimed to evaluate the role of ultrasonographic parameters including lung ultrasound and inferior vena cava (IVC) measurements as practical methods of volume status assessment in children on hemodialysis by comparing them with established techniques, such as clinical evaluation and bioimpedance spectroscopy. A prospective cross-sectional study compared pre- and post-dialysis volume status using bioimpedance spectroscopy (BIS) parameters and clinical data with ultrasonographic lung B-lines and IVC parameters in children on regular hemodialysis. A total 60 children (mean age 9.4 ± 2.8years) were enrolled. Twenty patients (33.3%) were clinically overloaded to varying degrees (17 patients had mild to moderate signs of fluid overload and 3 patients had moderate to severe signs of fluid overload). All other patients (66.7%) were clinically euvolemic. Sonographic parameters were significantly lower post-dialysis than pre-dialysis, including lung B-line count and IVC diameter. IVC collapsibility index mean was significantly higher post-dialysis than pre-dialysis. There was a significant correlation between the lung B-line count, IVC parameters, and BIS-measured overhydration both before and after hemodialysis. Nine patients had ≥ 8 B-lines post-dialysis, only three of them were hypertensive. Clinical criteria alone are not specific for determining accurate fluid status in pediatric hemodialysis patients. Lung B-line score, IVC parameters, and BIS may be complementary to each other and to clinical data. Lung B-lines outperform IVC measurements and BIS in subclinical volume overload detection in pediatric hemodialysis patients.

A New Methodology for the Oxygen Measurement in Lung Tissue of an Aged Ferret Model Proves Hypoxia During COVID-19.

Oxygen as a key element has a high impact on cellular processes. Infection with a pathogen such as SARS-CoV-2 and following inflammation may lead to hypoxic conditions in tissue that impact cellular responses. To develop optimized translational in vitro models for a better understanding of physiologic and pathophysiologic oxygen conditions, it is a prerequisite to determine oxygen levels generated in vivo. Our study objective was the establishment of an invasive method for oxygen measurements using a luminescence-based microsensor to determine the dissolved oxygen in the lung tissue of ferrets as animal models for SARS-CoV-2 research. In analogy to humans, aged ferrets are more likely to show clinical signs after SARS-CoV-2 infection compared to young animals. To investigate oxygen levels during a respiratory viral infection, we intratracheally infected nine aged (3-year-old) ferrets with SARS-CoV-2. The aged SARS-CoV-2 infected ferrets showed mild to moderate clinical signs associated with prolonged viral RNA shedding until 14 days post infection (dpi). SARS-CoV-2 infected ferrets showed histopathologic lung lesion scores that significantly negatively correlated with oxygen levels in lung tissue. At 4 dpi, oxygen levels in lung tissue were significantly lower (mean %O2 of 3.89 ≙ ≈ 27.78 mmHg) compared to the negative control group (mean %O2 of 8.65 ≙ ≈ 61.4 mmHg). In summary, we succeeded in determining the pathophysiologic oxygen conditions in the lung tissue of aged SARS-CoV-2-infected ferrets. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/). .

Isolation and pathogenicity comparison of two novel natural recombinant porcine reproductive and respiratory syndrome viruses with different recombination patterns in Southwest China.

Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic losses in the swine industry. Frequent mutations and recombinations account for PRRSV immune evasion and the emergence of novel strains. In this study, we isolated and characterized two novel PRRSV-2 strains from Southwest China exhibiting distinct recombination patterns. They were designated SCABTC-202305 and SCABTC-202309. Phylogenetic results indicated that SCABTC-202305 was classified as lineage 8, and SCABTC-202309 was classified as lineage 1.8. Amino acid mutation analysis identified unique amino acid substitutions and deletions in ORF5 and Nsp2 genes. The results of the recombination analysis revealed that SCABTC-202305 is a recombinant with JXA1 as the major parental strain and NADC30 as the minor parental strain. At the same time, SCABTC-202309 is identified as a recombinant with NADC30 as the major parental strain and JXA1 as the minor parental strain. In this study, we infected piglets with SCABTC-202305, SCABTC-202309, or mock inoculum (control) to study the pathogenicity of these isolates. Although both isolated strains were pathogenic, SCABTC-202305-infected piglets exhibited more severe clinical signs and higher mortality, viral load, and antibody response than SCABTC-202309-infected piglets. SCABTC-202305 also caused more extensive lung lesions based on histopathology. Our findings suggest that the divergent pathogenicity observed between the two novel PRRSV isolates may be attributed to variations in the genetic information encoded by specific genomic regions. Elucidating the genetic determinants governing PRRSV virulence and transmissibility will inform efforts to control this devastating swine pathogen.IMPORTANCEPorcine reproductive and respiratory syndrome virus (PRRSV) is one of the most critical pathogens impacting the global swine industry. Frequent mutations and recombinations have made the control of PRRSV increasingly difficult. Following the NADC30-like PRRSV pandemic, recombination events involving PRRSV strains have further increased. We isolated two novel field PRRSV recombinant strains, SCABTC-202305 and SCABTC-202309, exhibiting different recombination patterns and compared their pathogenicity in animal experiments. The isolates caused higher viral loads, persistent fever, marked weight loss, moderate respiratory clinical signs, and severe histopathologic lung lesions in piglets. Elucidating correlations between recombinant regions and pathogenicity in these isolates can inform epidemiologic tracking of emerging strains and investigations into viral adaptive mechanisms underlying PRRSV immunity evasion. Our findings underscore the importance of continued genomic surveillance to curb this economically damaging pathogen.

Tarsometatarsal osteoarthritis. A rare location of osteoarticular tuberculosis

Osteoarticular tuberculosis is one of the causes of subacute or chronic arthritis. Its most common location is the spine which is affected in 50% of cases, followed by the peripheral joints. Foot involvement represents a very rare location. The presence of certain arguments allows us to suspect the tuberculous origin of osteoarticular damage, among which we can cite its occurrence in a particular area, especially immunocompromised people following HIV or immunosuppressive treatment, residents of endemic areas, the dragging nature, over several months or even years of pain which is not very intense with moderate local inflammatory signs, as well as the fixity of osteoarticular damage. This article reports the case of a patient with lupus who developed one of the rarest locations of osteo-articular tuberculosis of the foot, during which the absence of respiratory symptoms and of specific joint manifestations were a source of diagnostic delay.

Optimal intestinal graft selection for reconstruction of extended ureteral stricture: an animal model study

Introduction. The prevalence of patients with extended ureteral strictures has been steadily increasing over the past decades. When it is not possible to perform reconstruction with the tissues of the urinary system, the best solution is intestinal replacement plasty. However, despite the great world experience, the search for the optimal method of intestinal reconstruction does not stop, which determines the relevance of conducting an experimental prospective study.Objective. To evaluate morphological changes in renal parenchyma after ureteral replacement reconstruction by segments of small and large intestine.Materials &amp; methods. Fifteen white giant rabbits (6-months-old, weighing 5 kg) were divided into three groups. Group A (n = 5) underwent small intestine [ilealplasty] replacement plasty. Group B (n = 5) double-flap ileoplasty using the Yang-Monti technique. Group C (n = 5) – large intestine [coloplasy] ureteral reconstruction. Before the operation and before withdrawal from the experiment, the level of creatinine and electrolytes was assessed, kidney ultrasound was performed on days 2, 5, 10. Excretory urography was performed to assess the patency of the anastomoses. Animals were withdrawn from the experiment from day 10 to 30. The material used for morphological study included kidneys from the operated and intact sides, proximal and distal anastomoses.Results. No increase in creatinine level, metabolic disorders were detected in animals. According to ultrasound data, hydronephrosis developed in all animals on day 2 and remained unchanged during the entire follow-up. Group A: no complications were detected. Histologically, the renal parenchyma showed moderate signs of chronic inflammation, single foci of lymphoid infiltration, but there were no irreversible processes in the form of necrosis and sclerosis. Group B: complications — stricture in the anastomosis area of the detubularised fragments and necrosis of the small intestine due to compression of the mesentery by the graft vascular stem. Histologically there were marked dilatation of the tubules at all levels, enlargement of the Bowman-Shumlansky capsule, as well as signs of moderate inflammatory process, there were hydropic and hyaline-droplet dystrophy, tubular necrosis foci. Group C: complications — accumulation of a significant amount of grit, mucus, and fibrin in the colocystoanastomosis area. Histologically, the renal parenchyma showed a marked inflammatory process, in particular, purulent inflammation with demarcation zones, infiltration with polymorphonuclear leukocytes and bacterial cells, foci of necrosis and sclerosis of both stroma and tubules, dilatation of tubules and Bowman-Schumlansky capsules.Conclusion. The use of an unchanged ileal-graft reconstruction of an extended ureteral defect showed acceptable histological results in an animal model, which confirms the feasibility of its use in clinical practice. The absence of foci of necrosis and fibrosis in the renal parenchyma indicates the preserved functional potential, which suggests the stabilization of renal function in the long term.

561 - Dupilumab treatment reduces signs in patients with atopic hand and foot dermatitis: results from a phase 3, randomized, double-blind, placebo-controlled trial

Abstract Introduction/Background Dupilumab has previously shown overall efficacy in treating atopic hand and foot dermatitis. Objective To report the effect of dupilumab treatment on individual signs of atopic hand and foot dermatitis. Methods The phase 3, randomized, double-blind LIBERTY-AD-HAFT (NCT04417894) trial enrolled patients aged ≥12 years with moderate-to-severe (Investigator’s Global Assessment [IGA] score of 3/4) atopic hand and foot dermatitis. Patients were randomized to dupilumab monotherapy 300 mg every 2 weeks (q2w) in adults; 200/300 mg q2w in adolescents, or placebo for 16 weeks. This analysis presents the proportion of patients reporting absent, mild, moderate, or severe erythema, scaling/flaking, lichenification, vesiculation/erosion, edema, and fissures, assessed by the modified total lesion sign score (mTLSS) in hands and feet. Results At baseline, most patients had scores of moderate or severe signs on their hands. Of the 133 patients enrolled, over 65% of patients treated with dupilumab (n = 67) achieved an absent or mild score by Week 16 in each of the signs/symptoms assessed. Proportion of patients with absent or mild hand scores increased from baseline to Week 16 in erythema (9% vs 71.6%), scaling/flaking (16.4% vs 74.7%), lichenification (4.5% vs 65.6%), vesiculation/erosion (43.3% vs 89.6%), edema (44.7% vs 86.6%), and fissures (23.9% vs 83.5%). Proportion of patients with absent or mild foot scores increased from baseline to Week 16 in erythema (56.7% vs 80.6%), scaling/flaking (56.7% vs 82.1%), lichenification (53.8% vs 82.1%), vesiculation/erosion (76.1% vs 86.6%), edema (76.1% vs 88.1%), and fissures (77.6% vs 86.6%). Safety was consistent with the known dupilumab safety profile in patients with atopic dermatitis. Conclusions Dupilumab treatment in patients improves signs of hand and foot dermatitis, including erythema, scaling/flaking, lichenification, vesiculation/erosion, edema, and fissures.

Immune-Related Adverse Events of Immune Checkpoint Inhibitors.

Immune-related adverse events (irAEs) are toxicities that arise after the administration of monoclonal antibodies targeting immune checkpoints (immune checkpoint inhibitors [ICIs]) in patients with cancer. They can occur at any time after initiation of ICI treatment, with a broad clinical phenotype that can be organ-specific or systemic. Although most irAEs manifest as mild to moderate signs and symptoms, severe forms of irAEs can lead to irreversible organ failure and have acute life-threatening presentations. Treatment should be tailored to the specific organ involved and the severity. Glucocorticoids are the first-line treatment for most irAEs, with immunosuppressants and biologics mainly used as second-line treatments.

Newcastle Disease Virus strain XIV.2 Infection in Geese and Guinea fowls: A Comparative Pathological Study

Aim: The study evaluates the pathogenic potential of strain XIV.2 NDV in geese and guinea fowls experimentally. Methods: Forty birds, comprising 20 geese and 20 guinea fowls, aged seven weeks were randomly divided into four groups (A–D), kept in separate pens as follows: 10 Control geese, 10 Infected geese, 10 Control guinea fowls and 10 Infected guinea fowls. The birds in group B and D were inoculated with 0.2 mL of strain XIV.2 NDV inoculum (titre of 108.2/0.1 mL ELD50) intra-nasally, while those in group A and C were inoculated with phosphate buffered solution (PBS) intra-nasally respectively. Gross and histopathological procedures were performed using standard methods. Results: Revealed transient clinical signs without mortality in infected geese whereas moderate clinical signs with mortality were observed in infected guinea fowls. Gross lesions were mild in infected geese from 6 to 28 days post-inoculation, (dpi) and in infected guinea fowls at 3, 21 and 28 dpi, with moderate lesions observed from 6, 11, 12 and 14 dpi. Histopathological lesions in infected geese were moderate from 3 to 21 dpi, but mild at 28 dpi, whereas mild lesions were observed from 3 to 6 dpi, followed by moderate lesions from 9 to 28 dpi in infected guinea fowls. Conclusion: Morbidity and mortality due to strain XIV.2 NDV infection were moderate in guinea fowls, but inapparent and transient in geese. Therefore, free-ranging system commonly practice in the region should either be discouraged or vaccination of these species of birds should be encouraged.