An atlas of cells in the human tonsil.

Palatine tonsils are secondary lymphoid organs (SLOs) representing the first line of immunological defense against inhaled or ingested pathogens. We generated an atlas of the human tonsil composed of >556,000 cells profiled across five different data modalities, including single-cell transcriptome, epigenome, proteome, and immune repertoire sequencing, as well as spatial transcriptomics. This census identified 121 cell types and states, defined developmental trajectories, and enabled an understanding of the functional units of the tonsil. Exemplarily, we stratified myeloid slan-like subtypes, established a BCL6 enhancer as locally active in follicle-associated T and B cells, and identified SIX5 as putative transcriptional regulator of plasma cell maturation. Analyses of a validation cohort confirmed the presence, annotation, and markers of tonsillar cell types and provided evidence of age-related compositional shifts. We demonstrate the value of this resource by annotating cells from B cell-derived mantle cell lymphomas, linking transcriptional heterogeneity to normal B cell differentiation states of the human tonsil.

Communication, construction, and fluid control: lymphoid organ fibroblastic reticular cell and conduit networks.

Fibroblastic reticular cells (FRCs) are a crucial part of the stromal cell infrastructure of secondary lymphoid organs (SLOs). Lymphoid organ fibroblasts form specialized niches for immune cell interactions and thereby govern lymphocyte activation and differentiation. Moreover, FRCs produce and ensheath a network of extracellular matrix (ECM) microfibers called the conduit system. FRC-generated conduits contribute to fluid and immune cell control by funneling fluids containing antigens and inflammatory mediators through the SLOs. We review recent progress in FRC biology that has advanced our understanding of immune cell functions and interactions. We discuss the intricate relationships between the cellular FRC and the fibrillar conduit networks, which together form the basis for efficient communication between immune cells and the tissues they survey.

Increased prevalence of Kidney cysts in individuals carrying heterozygous COL4A3 or COL4A4 pathogenic variants.

BACKGROUND: Clinical variability among individuals with heterozygous pathogenic/likely pathogenic (P/LP) variants in the COL4A3/COL4A4 genes (also called autosomal dominant Alport syndrome or COL4A3/COL4A4 related disorder) is huge; many individuals are asymptomatic or show microhematuria, while others may develop proteinuria and chronic kidney disease (CKD). The prevalence of simple kidney cysts (KC) in the general population varies according to age, and patients with advanced CKD are prone to have them. A possible association between heterozygous COL4A3, COL4A4, and COL4A5 P/LP variants and KC has been described in small cohorts. The presence of KC in a multicenter cohort of individuals with heterozygous P/LP variants in the COL4A3/COL4A4 genes is assessed in this study. METHODS: We evaluated the presence of KC by ultrasound in 157 individuals with P/LP variants in COL4A3 (40.7%) or COL4A4 (53.5%) without kidney replacement therapy. The association between presence of KC and age, proteinuria, eGFR, and causative gene was analyzed. Prevalence of KC was compared with historical case series in the general population. RESULTS: Half of the individuals with P/LP variants in COL4A3/COL4A4 showed KC, which is a significantly higher percentage than in the general population. Only 3.8% (6/157) had cystic nephromegaly. Age and eGFR showed an association with the presence of KC (p<0.001). No association was found between KC and proteinuria, sex, or causative gene. CONCLUSIONS: Individuals with COL4A3/COL4A4 P/LP variants are prone to develop KC more frequently than the general population, and their presence is related to age and to eGFR. Neither proteinuria, sex nor the causative gene influences the presence of KC in these individuals.

Results of Palliative Stenting in Malignant Superior Vena Cava Syndrome Analyzing Self-Expanding Stainless Steel and Nitinol Venous Bare Metal Stents.

PURPOSE: The purpose was to analyze the technical, clinical, and survival outcomes of our patients with malignant superior cava vein syndrome (SVCS) treated with endovascular approach and analyze the efficacy of different stent types used. MATERIAL AND METHODS: It is an observational, retrospective, single-center study. From 2006 to 2023, 42 patients (32 male, 10 female, mean age 62 years, age range, 41-87 years) underwent percutaneous stent placement for malignant SVCS. One stainless steel stent (Wallstent) and 2 venous nitinol stent type (Sinus-XL, Venovo) were used. Follow-up mean was 276 days. RESULTS: A total of 53 stents were deployed. Clinical success was 97.6% in less 24 hours. Technical success was achieved in 97.6%. No complications were found except 1 patient died during the procedure due to stent migration and atrial dissociation (2.3%). Overall intraprocedural stent migration rate was 11.9% (18.8% stainless steel stent, 9.6% nitinol stent, p>0.05). Overall survival rates were 87.8%, 41.99%, and 34.12%, and overall primary patency rates were 100%, 93.3%, 91.6% at 1, 6, and 12 months, respectively. CONCLUSIONS: Endovascular treatment is a safe and effective therapeutic option for SVCS with high technical and clinical success rates and low complication and recurrence rates. CLINICAL IMPACT: The malignant superior cava vein syndrome is a rare clinical entity treated classically with radiation and chemotherapy with a slower response, or surgical bypass, which is an aggressive surgical technique. Endovascular treatment offers a low-invasive technique with quick clinical resolution and good permeability results. However, further studies are lacking to deal with procedure technical characteristics, stent type used, technical complications, and medium- and long-term patency studies. This study aims to evaluate all these items, analysing self-expanding stainless steel and nitinol venous bare metal stents, and add value to endovascular treatment, confirming the good results of this technique.

Pembrolizumab-induced agranulocytosis.

INTRODUCTION: With the widespread use of anti-programmed death-1 monoclonal antibodies, such as pembrolizumab, rare side effects appear in clinical practice. CASE REPORT: We report the case of a man diagnosed with non-keratinizing squamous lung carcinoma stage IVB with programmed death-ligand 1 70% who developed agranulocytosis 10 days after a single dose of pembrolizumab as monotherapy. MANAGEMENT AND OUTCOME: Pembrolizumab was discontinued immediately. Grade 4 neutrophil decrease is mentioned in the product information sheet as a rare side effect. The patient was admitted in poor physical condition with grade 4 neutropenic fever, mucositis and anemia. Agranulocytosis did not improve despite treatment with granulocyte colony-stimulating factor, intravenous corticosteroids and intravenous immunoglobulins. He experienced a rapid worsening and died 3 weeks after admission. The causal relationship between pembrolizumab and the appearance of agranulocytosis was determined as possible according to Naranjo's modified Karch and Lasagna's imputability algorithm. DISCUSSION: Hematologic immune-related adverse events are uncommon but important side effects among patients treated with immune checkpoint inhibitors. Agranulocytosis and neutropenia are infrequently reported but can be life-threatening. The main approach for agranulocytosis consists of intravenous corticosteroids, granulocyte colony-stimulating factors and blood products. Depending on bone marrow characteristics, treatments for refractory patients include intravenous immunoglobulins or cyclosporine. After an immune-related adverse event, benefits and risks must be considered before continuation with an immune checkpoint inhibitor. Detection and communication of adverse drug reactions to the Pharmacovigilance Systems have special relevance for rare side effects.

Delayed diagnosis of Loeys-Dietz syndrome revealed through atrial septal defect with pulmonary artery dilation.

Loeys-Dietz syndrome (LDS) is an autosomal-dominant connective tissue disorder associated with mutations in the transforming growth factor ß receptor. It is characterized by distinctive craniofacial changes, skeletal features, and cardiovascular complications. We present a case of a 24-year-old male with development delay and a one-year history of progressively worsening dyspnea on moderate exertion and orthopnea. Echocardiography revealed right atrial and right ventricle dilation, right ventricle hypertrophy, atrial septal defect, and aneurysmal dilation of the pulmonary artery trunk. This case underscores the importance of early detection and comprehensive imaging in patients suspected of having LDS, particularly considering the potential for atypical vascular manifestations.

Unbiased Human Kidney Tissue Proteomics Identifies Matrix Metalloproteinase 7 as a Kidney Disease Biomarker.

SIGNIFICANCE STATEMENT: Although gene expression changes have been characterized in human diabetic kidney disease (DKD), unbiased tissue proteomics information for this condition is lacking. The authors conducted an unbiased aptamer-based proteomic analysis of samples from patients with DKD and healthy controls, identifying proteins with levels that associate with kidney function (eGFR) or fibrosis, after adjusting for key covariates. Overall, tissue gene expression only modestly correlated with tissue protein levels. Kidney protein and RNA levels of matrix metalloproteinase 7 (MMP7) strongly correlated with fibrosis and with eGFR. Single-cell RNA sequencing indicated that kidney tubule cells are an important source of MMP7. Furthermore, plasma MMP7 levels predicted future kidney function decline. These findings identify kidney tissue MMP7 as a biomarker of fibrosis and blood MMP7 as a biomarker for future kidney function decline. BACKGROUND: Diabetic kidney disease (DKD) is responsible for close to half of all ESKD cases. Although unbiased gene expression changes have been extensively characterized in human kidney tissue samples, unbiased protein-level information is not available. METHODS: We collected human kidney samples from 23 individuals with DKD and ten healthy controls, gathered associated clinical and demographics information, and implemented histologic analysis. We performed unbiased proteomics using the SomaScan platform and quantified the level of 1305 proteins and analyzed gene expression levels by bulk RNA and single-cell RNA sequencing (scRNA-seq). We validated protein levels in a separate cohort of kidney tissue samples as well as in 11,030 blood samples. RESULTS: Globally, human kidney transcript and protein levels showed only modest correlation. Our analysis identified 14 proteins with kidney tissue levels that correlated with eGFR and found that the levels of 152 proteins correlated with interstitial fibrosis. Of the identified proteins, matrix metalloprotease 7 (MMP7) showed the strongest association with both fibrosis and eGFR. The correlation between tissue MMP7 protein expression and kidney function was validated in external datasets. The levels of MMP7 RNA correlated with fibrosis in the primary and validation datasets. Findings from scRNA-seq pointed to proximal tubules, connecting tubules, and principal cells as likely cellular sources of increased tissue MMP7 expression. Furthermore, plasma MMP7 levels correlated not only with kidney function but also associated with prospective kidney function decline. CONCLUSIONS: Our findings, which underscore the value of human kidney tissue proteomics analysis, identify kidney tissue MMP7 as a diagnostic marker of kidney fibrosis and blood MMP7 as a biomarker for future kidney function decline.

The Prevalence of Acute Compartment Syndrome in Pediatric Tibial Tubercle Fractures.

OBJECTIVE: Tibial tubercle fractures are a unique class of pediatric orthopaedic injuries that frequently necessitate surgical treatment and strict monitoring due to the associated risk of acute compartment syndrome (ACS). However, current literature is conspicuously limited in its ability to estimate the risk of ACS after these fractures. Therefore, the purpose of this study is to utilize a nationwide database to estimate the prevalence of ACS after pediatric tibial tubercle fractures. METHODS: We utilized the Healthcare Cost and Utilization Project's Kids' Inpatient Database (2019) to identify all pediatric patients, 18 years of age and under, with isolated tibial tubercle fractures (International Classification of Diseases, 10th revision Clinical Modification S82.151-S82.156) and ACS (T79.A0, T79.A2, T79.A29). Patients were excluded if they had additional lower extremity injuries (ie, tibial shaft, plateau, etc). A subanalysis was conducted for those undergoing fasciotomy, with and without an ACS diagnosis. RESULTS: Among the 591 isolated tibial tubercle fractures, there were 8 ACS cases for a prevalence of 1.35%. There were 22 (3.72%) additional cases of fasciotomy without an ACS diagnosis. All ACS cases were diagnosed during the original hospitalization; all were male and had closed fractures. The cohort included 469 teenagers (13+ years) and 77 pre-teens, with 40 females and 506 males. Racial demographics: 132 white, 232 black, 112 Hispanic, 15 Asian, 4 Native American, 23 unknown, and 28 others. No significant associations were found between ACS and age, race, insurance status, mechanism of injury, or hospital region. CONCLUSION: The rate of ACS in pediatric tibial tubercle fractures appears to be much lower than previously reported, at 1.35%. However, the nearly three-fold higher prevalence of fasciotomy without an ACS diagnosis, suggests a generous use of prophylactic fasciotomies and/or an undercharacterization of actual ACS cases from miscoding. This is the first and largest study to employ a nationally representative database to investigate the prevalence of ACS after tibial tubercle fractures. LEVEL OF EVIDENCE: Level III.

A comparison of three techniques for the osteosynthesis after minimal invasive osteotomies for hallux valgus.

PURPOSE: Third and fourth-generation minimal invasive osteotomies (MIO) for the treatment of hallux valgus (HV) have become popular procedures worldwide with promising results due to the improvement in the fixation method. The tricortical cannulated screw placement remains a complex procedure that is technically challenging and requires a long skill learning curve with high radiation exposure mainly in the form of intensifier shots (IS) required for the MIO fixation. This study aims to compare the number of X-ray IS required using three different techniques for the cannulated guide placement. METHODS: A retrospective cross-sectional observational and comparative study was conducted to assess the number of X-rays IS required for correct cannulated screw guide placement using three different techniques: traditional perforator, the drill and joystick, and K-wire first techniques. RESULTS: A total of 53 MIS procedures from thirty-one patients in two different hospitals were included. IS X-rays were 155.1 ± 29.7 in the traditional technique (n = 14), 143.0 ± 43.2 in the drill and joystick technique (n = 22), and 85 ± 18.7 in the K-wires first technique (n = 17), p = < 0.001 using one-way ANOVA. CONCLUSIONS: The K-wire first technique statistically significantly decreases X-ray IS numbers p ≤ 0.001. There were no statistically significant differences between the traditional (after osteotomy K-wire placement) and the drill and joystick techniques (p = 0.36).

Physicochemical and Volatile Compounds Analysis of Fruit Wines Fermented with Saccharomyces cerevisiae: FTIR and Microscopy Study with Focus on Anti-Inflammatory Potential.

The growing trend in fruit wine production reflects consumers' interest in novel, diverse drinking experiences and the increasing demand for healthier beverage options. Fruit wines made from kiwi, pomegranates, and persimmons fermented using S. bayanus Lalvin strain EC1118 demonstrate the versatility of winemaking techniques. Kiwifruit, persimmon, and pomegranate wines were analyzed using HPLC and GC-TOFMS analyses to determine their concentrations of phenolic acids and volatile compounds. These results were supported by Fourier transform infrared (FTIR) spectroscopy to characterize and compare chemical shifts in the polyphenol regions of these wines. The wines' characterization included an anti-inflammatory assay based on NO, TNF-alpha, and IL-6 production in the RAW 264.7 macrophage model. FTIR spectroscopy predicted the antioxidant and phenolic contents in the wines. In terms of polyphenols, predominantly represented by chlorogenic, caffeic, and gallic acids, pomegranate and kiwifruit wines showed greater benefits. However, kiwifruit wines exhibited a highly diverse profile of volatile compounds. Further analysis is necessary, particularly regarding the use of other microorganisms in the fermentation process and non-Saccharomyces strains methods. These wines exhibit high biological antioxidant potential and health properties, providing valuable insights for future endeavors focused on designing healthy functional food products.

Sustainable Production of Biofuels and Biochemicals via Electro-Fermentation Technology.

The energy crisis and climate change are two of the most concerning issues for human beings nowadays. For that reason, the scientific community is focused on the search for alternative biofuels to conventional fossil fuels as well as the development of sustainable processes to develop a circular economy. Bioelectrochemical processes have been demonstrated to be useful for producing bioenergy and value-added products from several types of waste. Electro-fermentation has gained great attention in the last few years due to its potential contribution to biofuel and biochemical production, e.g., hydrogen, methane, biopolymers, etc. Conventional fermentation processes pose several limitations in terms of their practical and economic feasibility. The introduction of two electrodes in a bioreactor allows the regulation of redox instabilities that occur in conventional fermentation, boosting the overall process towards a high biomass yield and enhanced product formation. In this regard, key parameters such as the type of culture, the nature of the electrodes as well as the operating conditions are crucial in order to maximize the production of biofuels and biochemicals via electro-fermentation technology. This article comprises a critical overview of the benefits and limitations of this emerging bio-electrochemical technology and its contribution to the circular economy.

Effect of extracorporeal shockwave therapy on plantar fascia thickness in plantar fasciitis: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Extracorporeal shockwave therapy (ESWT) has been used as a therapeutic option for plantar fasciitis. The objective was to investigate the effect of ESWT over the plantar fascia thickness. METHODS: MEDLINE, Embase, Web of Science, and SCOPUS databases were searched for randomized controlled trials evaluating the effect of ESWT in patients with plantar fasciitis, comparing ESWT with another treatment. Meta-analysis was conducted using a random-effects model and the generic inverse variance method. Meta-regression and subgroup analyses were also carried out. RESULTS: A total of 14 studies (867 participants) were included. ESWT significantly decreased plantar fascia thickness (weighted mean difference [WMD], -0.21 mm [95% CI -0.39, -0.02]; p = 0.03). No significant improvement in pain was observed (WMD, -0.51 cm [95% CI -1.04, 0.01]; p = 0.06) compared with non-surgical interventions. CONCLUSIONS: Our results suggest that plantar fascia thickness is significantly decreased after ESWT intervention in patients with plantar fasciitis. However, pain relief was not significantly improved compared to other non-surgical interventions.

Proximal humeral fractures: association between displacement and fatty degeneration of the supraspinatus muscle.

INTRODUCTION: To evaluate the relationship between initial displacement in proximal humeral fractures and fatty degeneration of the rotator cuff measured by CT according to the Goutallier classification. MATERIAL AND METHODS: This cross-sectional observational study evaluated patients with proximal humeral fractures over a six-month period. The study included patients ≥ 18 years old with complete radiological views (anteroposterior, lateral, and Grashey) and a CT scan of the affected shoulder; previous fracture or ipsilateral shoulder surgery were excluded. Neer's classification system and Goutallier stages were used to evaluate the patients. Demographic data were collected and, two groups were analysed according to age (≤ 50 years and > 50 years). RESULTS: Sixty-two patients were included (m = 36, f = 26, ratio 1.3:1); seven patients were excluded. Male patients (36, 58.1%), patients older than 50 years (33, 53.2%) and a low-energy injury mechanism (36, 58.1%) were the most frequent cases. According to the Neer system, the most common proximal humerus fracture was fracture-dislocation in 17 (27.4%) cases. The most common stage in Goutallier's classification was I (some fatty streaks) in 22 (35.4%) cases. Younger patients (≤ 50 years) had more displaced fractures with low fatty degeneration (p = < 0.001) than older patients (> 50 years), who had minimally displaced fractures with greater fatty degeneration (p = 0.567). CONCLUSIONS: High-energy mechanisms are associated with younger patients and a more displaced fracture according to the Neer classification. Older patients had a more advanced Goutallier stage and lesser displaced fracture. We should consider a more aggressive approach in the treatment of non-displaced fractures in elderly patients, less conservative and more surgical management, to obtain a better clinical evolution after the treatment of these kinds of fractures. LEVEL OF EVIDENCE: IV.

Quantitative Volumetric Measurements of Bone Grafting Sites Within the Lower Extremity on Computed Tomography Scans.

The anterior iliac crest is one of the most used options; however, pain and other complications have been reported. Other options for bone harvest in the lower extremity, such as the proximal tibia and calcaneus, can be useful sites for bone grafting. Computed tomography angiography images of the lower extremity were analyzed using 3-D Slicer™ medical imaging software, creating an advanced 3-dimensional model. Bone volume (cm3) and bone mineral density (Hounsfield units) were measured from the cancellous bone in the anterior iliac crest, posterior iliac crest, proximal tibia, and the calcaneus. Fifteen studies were included. The total volume measured it was of 61.88 ± 14.15 cm3, 19.35 ± 4.16 cm3, 32.48 ± 7.49 cm3, 26.40 ± 7.18 cm3, for the proximal tibia, anterior and posterior iliac crest, and calcaneus, respectively. Regarding Hounsfield units, the densities were 116 ± 58.77, 232.4 ± 68.65, 214.4 ± 74.45, 170.5 ± 52.32, for proximal tibia, anterior and posterior iliac crest, and calcaneus. The intraclass correlation coefficients were in average >0.94. In conclusion, the proximal tibia has more cancellous bone than the anterior and posterior iliac crest. The calcaneus has more cancellous bone than the anterior iliac crest. Bone mineral density was highest in the anterior iliac crest and in proximal tibia was the lowest value.

Hamstring muscle injury is preceded by a short period of higher running demands in professional football players.

The aim of this study was to examine match running patterns before a hamstring muscle injury occurs during a match in male professional football players. A total of 281 male professional football players belonging to 7 teams from LaLiga were prospectively monitored over three seasons. Among these, 36 players suffered a non-contact hamstring muscle injury during an official match. The injuries were recorded by the medical staff, including the minute when the injury occurred. Running distances at different speed thresholds for 5 min and 15 min before the injury were compared to mean values of the previous 5 matches for the same time points. There were a total of 44 non-contact hamstring muscle injuries, which represents a hamstring muscle injury incidence of 3.34 injuries/1000 h of match exposure. The average time loss for these injuries was 33 ± 28 days (range 7 to 117 days). In the 15 min prior to the injury, players ran a similar distance as in control matches (p from 0.22 to 0.08). However, players ran a greater distance in the 5-min period before the injury than in control matches at 21.0-23.9 km/h (p < 0.001) and at ≥ 24 km/h (p < 0.001). The odds ratio for a hamstring muscle injury was 7.147 for those players who ran > 30.0 m at ≥ 21 km/h in a 5-min period (p < 0.001). Hamstring muscle injuries during competition were preceded by 5 min of higher running demands at > 21 km/h, compared with control matches. This suggests that a short period of unusual running increases the risk of hamstring muscle injury in professional football players.

Fibroblastic reticular cell response to dendritic cells requires coordinated activity of podoplanin, CD44 and CD9.

In adaptive immunity, CLEC-2+ dendritic cells (DCs) contact fibroblastic reticular cells (FRCs) inhibiting podoplanin-dependent actomyosin contractility, permitting FRC spreading and lymph node expansion. The molecular mechanisms controlling lymph node remodelling are incompletely understood. We asked how podoplanin is regulated on FRCs in the early phase of lymph node expansion, and which other proteins are required for the FRC response to DCs. We find that podoplanin and its partner proteins CD44 and CD9 are differentially expressed by specific lymph node stromal populations in vivo, and their expression in FRCs is coregulated by CLEC-2 (encoded by CLEC1B). Both CD44 and CD9 suppress podoplanin-dependent contractility. We find that beyond contractility, podoplanin is required for FRC polarity and alignment. Independently of podoplanin, CD44 and CD9 affect FRC-FRC interactions. Furthermore, our data show that remodelling of the FRC cytoskeleton in response to DCs is a two-step process requiring podoplanin partner proteins CD44 and CD9. Firstly, CLEC-2 and podoplanin binding inhibits FRC contractility, and, secondly, FRCs form protrusions and spread, which requires both CD44 and CD9. Together, we show a multi-faceted FRC response to DCs, which requires CD44 and CD9 in addition to podoplanin.

Barriers to and Outcomes of Initiating Clinical Research at Two Trauma Centers in Mexico.

INTRODUCTION: Despite efforts to advance clinical research through collaboration between Latin and North American partners, there remains persistent barriers to performing investigative work. To overcome these obstacles, a team of over 100 surgeon-leaders from 18 Latin American countries founded the Asociación de Cirujanos Traumatólogos de las Américas (ACTUAR). One of ACTUAR's first major collaborative projects, initiated in 2018, was a prospective, observational, multicenter study evaluating quality of life after open tibia fracture management. The current study identified common barriers experienced during the initiation of this study, as exemplified through two sites in Mexico. The study aims to identify obstacles to proactively overcome these in future collaborative work. METHODS: Two research assistants from University of California, San Francisco and two research coordinators from Mexico were recruited to share their experiences, identify common barriers experienced during site enrollment and on-boarding for the ACTUAR open tibia study, and discuss possible solutions. RESULTS: Barriers were organized into three categories: structural, logistical, and intrapersonal. Structural barriers included differences in patient populations and resources between private and public hospitals. Logistical barriers included ambiguous ethical review processes, internet availability, and low patient follow-up. Primary enrollment as a resident responsibility led to some intrapersonal barriers. Potential solutions were identified for each barrier and agreed upon by all collaborators. CONCLUSIONS: Multiple barriers were identified by research personnel who initiated a prospective surgical clinical research study in Mexico. Through collaborative approaches, many potential solutions may help overcome these barriers and build locally led research capacity in Latin America.

Host-pathogen interaction involving cytoskeleton changes as well as non-coding regulation as primary mechanisms for SRS resistance in Atlantic salmon.

The salmonid rickettsial syndrome (SRS) is a systemic bacterial infection caused by Piscirickettsia salmonis that generates significant economic losses in Atlantic salmon (Salmo salar) aquaculture. Despite this disease's relevance, the mechanisms involved in resistance against P. salmonis infection are not entirely understood. Thus, we aimed at studying the pathways explaining SRS resistance using different approaches. First, we determined the heritability using pedigree data from a challenge test. Secondly, a genome-wide association analysis was performed following a complete transcriptomic profile of fish from genetically susceptible and resistant families within the challenge infection with P. salmonis. We found differentially expressed transcripts related to immune response, pathogen recognition, and several new pathways related to extracellular matrix remodelling and intracellular invasion. The resistant background showed a constrained inflammatory response, mediated by the Arp2/3 complex actin cytoskeleton remodelling polymerization pathway, probably leading to bacterial clearance. A series of biomarkers of SRS resistance, such as the beta-enolase (ENO-ß), Tubulin G1 (TUBG1), Plasmin (PLG) and ARP2/3 Complex Subunit 4 (ARPC4) genes showed consistent overexpression in resistant individuals, showing promise as biomarkers for SRS resistance. All these results together with the differential expression of several long non-coding RNAs show the complexity of the host-pathogen interaction of S. salar and P. salmonis. These results provide valuable information on new models describing host-pathogen interaction and its role in SRS resistance.

Molecular Alumo- and Gallosilicate Hydrides Functionalized with Terminal M(NR2)3 and Bridging M(NR2)2 (M = Ti, Zr, Hf; R = Me, Et) Moieties.

A general synthetic strategy for the systematic synthesis of group 4 MIV heterometallic complexes LMIII(H)(µ-O)Si(µ-O)(OtBu)2}nMIV(NR2)4-n (L = {[HC{C(Me)N(2,6-iPr2C6H3)}2; MIII = Al or Ga; n = 1 or 2; MIV = Ti, Zr, Hf; R = Me, Et), based on alumo- or gallosilicate hydride ligands bearing a Si-OH moiety, is presented. The challenging isolation of these metalloligands involved two strategies. On the one hand, the acid-base reaction of LAlH2 with (HO)2Si(OtBu)2 yielded LAlH(µ-O)Si(OH)(OtBu)2 (1), while on the other hand, the oxidative addition of (HO)2Si(OtBu)2 to LGa produced the gallium analog (2). These metalloligands successfully stabilized two hydrogen atoms with different acid-base properties (MIII-H and SiO-H) in the same molecule. Reactivity studies between 1 and 2 and group 4 amides MIV(NR2)4 (MIV = Ti, Zr, Hf; R = Me, Et) and tuning the reactions conditions and stoichiometry led to isolation and structural characterization of heterometallic complexes 3-11 with a 1:1 or 2:1 metalloligand/MIV ratio. Notably, some of these molecular heterometallic silicate complexes stabilize for the first time terminal (O3Si-O-)MIV(NR2)3 moieties known from single-site silica-grafted species. Furthermore, the aluminum-containing heterometallic complexes possess Al-H vibrational energies similar to those reported for modified alumina surfaces, which makes them potentially suitable models for the proposed MIV species grafted onto silica/alumina surfaces with hydride and dihydride architectures.

Survey on helminths of bats in the Yucatan Peninsula: infection levels, molecular information and host-parasite networks.

Helminth species of Neotropical bats are poorly known. In Mexico, few studies have been conducted on helminths of bats, especially in regions such as the Yucatan Peninsula where Chiroptera is the mammalian order with the greatest number of species. In this study, we characterized morphologically and molecularly the helminth species of bats and explored their infection levels and parasite­host interactions in the Yucatan Peninsula, Mexico. One hundred and sixty-three bats (representing 21 species) were captured between 2017 and 2022 in 15 sites throughout the Yucatan Peninsula. Conventional morphological techniques and molecular tools were used with the 28S gene to identify the collected helminths. Host­parasite network analyses were carried out to explore interactions by focusing on the level of host species. Helminths were found in 44 (26.9%) bats of 12 species. Twenty helminth taxa were recorded (7 trematodes, 3 cestodes and 10 nematodes), including 4 new host records for the Americas. Prevalence and mean intensity of infection values ranged from 7.1 to 100% and from 1 to 56, respectively. Molecular analyses confirmed the identity of some helminths at species and genus levels; however, some sequences did not correspond to any of the species available on GenBank. The parasite­host network suggests that most of the helminths recorded in bats were host-specific. The highest helminth richness was found in insectivorous bats. This study increases our knowledge of helminths parasitizing Neotropical bats, adding new records and nucleotide sequences.