Effects of rainfall on Culex mosquito population dynamics.

The dynamics of a mosquito population depends heavily on climatic variables such as temperature and precipitation. Since climate change models predict that global warming will impact on the frequency and intensity of rainfall, it is important to understand how these variables affect the mosquito populations. We present a model of the dynamics of a Culex quinquefasciatus mosquito population that incorporates the effect of rainfall and use it to study the influence of the number of rainy days and the mean monthly precipitation on the maximum yearly abundance of mosquitoes Mmax. Additionally, using a fracturing process, we investigate the influence of the variability in daily rainfall on Mmax. We find that, given a constant value of monthly precipitation, there is an optimum number of rainy days for which Mmax is a maximum. On the other hand, we show that increasing daily rainfall variability reduces the dependence of Mmax on the number of rainy days, leading also to a higher abundance of mosquitoes for the case of low mean monthly precipitation. Finally, we explore the effect of the rainfall in the months preceding the wettest season, and we obtain that a regimen with high precipitations throughout the year and a higher variability tends to advance slightly the time at which the peak mosquito abundance occurs, but could significantly change the total mosquito abundance in a year.

Meniscal extrusion as booster of osteoarthritis.

Meniscal extrusion (ME) has shown to play a critical but still unclear role in osteoarthritis (OA) development. ME has been described as an important risk factor in the progression of knee OA, as it is involved in the thinning of articular cartilage, joint space narrowing, spontaneous osteonecrosis of the knee and subchondral bone marrow lesions. Meniscal damage of any degree of severity could cause ME in both compartments, but it is commonly associated with severe meniscal tears or root tears mainly in the medial meniscus. Magnetic resonance imaging is the most commonly used imaging modality in the assessment of ME, while ultrasonography may represent a valid alternative with high sensitivity and specificity. Conservative treatment for ME includes physical therapy and rehabilitation to maintain range of motion, corticosteroid injections and intra-articular injections of hyaluronic acid to provide short-term relief of knee pain. The goal of this study is to review standards of current diagnosis and treatment of ME and its relationship to knee OA.

Intrarticular injections of hyaluronic acid for trapezio-metacarpal osteoarthritis: a systematic review.

Osteoarthritis (OA) of the base of the thumb, also known as Trapezio-Metacarpal (TM) OA, is a disabling condition, which mainly affects women and manual workers. When TM OA is not adequately treated, patients develop deformity and loss of function of the thumb. The surgical approach is a widespread strategy to treat this condition, but there is still no consensus on the most effective procedure. Therefore, several conservative strategies are commonly used, such as nonsteroidal anti-inflammatory drugs (NSAIDs) administration, thumb strengthening exercise, splinting, steroid (CS) and hyaluronic acid (HA) intrarticular injections. The present review of the literature aims to summarize the available scientific evidence on the treatment of TM OA with injections of HA. Thirteen studies were included: 7 randomized controlled trials, 5 case series and a case-control study. Among these, 5 studies compared HA versus CS injection. Results from most of them reported better outcomes with HA injections in terms of function (strength) and joint motion, while CS injections had greater effect on pain; moreover, CS action was faster but shorter, while HA required more time to obtain a therapeutic benefit and lasted longer. In non-comparative articles, this trend was also confirmed. Indeed, the authors reported an improvement in pain relief up to six months. Similarly, all studies indicated hand function improvement over time, measured though DASH score, pincher and grip strength tests. Available data from included studies show that there is no clear evidence to suggest a treatment with HA injections as the best advisable non-operative treatment for TM OA. However, promising potentials were shown by the randomized controlled trials, suggesting that there is some benefit and less comorbidities with the administration of HA. Further research, such as trials evaluating larger cohorts with validated scores for long-term follow-up, is still necessary.

Circulating tumor DNA as an early marker of therapeutic response in patients with metastatic colorectal cancer.

BACKGROUND: Early indicators of treatment response in metastatic colorectal cancer (mCRC) could conceivably be used to optimize treatment. We explored early changes in circulating tumor DNA (ctDNA) levels as a marker of therapeutic efficacy. PATIENTS AND METHODS: This prospective study involved 53 mCRC patients receiving standard first-line chemotherapy. Both ctDNA and CEA were assessed in plasma collected before treatment, 3 days after treatment and before cycle 2. Computed tomography (CT) scans were carried out at baseline and 8-10 weeks and were centrally assessed using RECIST v1.1 criteria. Tumors were sequenced using a panel of 15 genes frequently mutated in mCRC to identify candidate mutations for ctDNA analysis. For each patient, one tumor mutation was selected to assess the presence and the level of ctDNA in plasma samples using a digital genomic assay termed Safe-SeqS. RESULTS: Candidate mutations for ctDNA analysis were identified in 52 (98.1%) of the tumors. These patient-specific candidate tissue mutations were detectable in the cell-free DNA from the plasma of 48 of these 52 patients (concordance 92.3%). Significant reductions in ctDNA (median 5.7-fold; P < 0.001) levels were observed before cycle 2, which correlated with CT responses at 8-10 weeks (odds ratio = 5.25 with a 10-fold ctDNA reduction; P = 0.016). Major reductions (≥10-fold) versus lesser reductions in ctDNA precycle 2 were associated with a trend for increased progression-free survival (median 14.7 versus 8.1 months; HR = 1.87; P = 0.266). CONCLUSIONS: ctDNA is detectable in a high proportion of treatment naïve mCRC patients. Early changes in ctDNA during first-line chemotherapy predict the later radiologic response.

Prevalence of carbapenem-resistant organisms and other Gram-negative MDRO in German ICUs: first results from the national nosocomial infection surveillance system (KISS).

PURPOSE: Standardized prevalence and incidence data on carbapenem-resistant organisms (CRO) and, as a relevant subgroup, carbapenem-resistant Enterobacteriaceae (CRE) are scarce. CRO-surveillance within the German nosocomial infection surveillance system (KISS) aims to provide epidemiological surveillance data on CRO colonizations and infections. METHODS: CRO-surveillance is part of a KISS-module for the surveillance of multidrug-resistant organisms (MDRO). MDRO-KISS methods require surveillance of all patients admitted to the ward and standardized documentation of imported and ICU-acquired cases. Data on all MDRO-carriers including colonization and infection with MDRO are collected. All presented data were routine data collected from January 1st 2013 until December 1st 2013 in accordance with the German Protection against Infection Act (IfSG). RESULTS: 341 ICUs submitted data on MDRO during the first year. In total, 5,171 cases of multidrug-resistant Gram-negative bacteria (MRGN) were identified. 848 were CRO (16%). 325 CRO-cases were acquired within the ICU (38%), and 373 CRO-patients had an infection (44%). CRO-prevalence was 0.29 per 100 patients. Acquisition rate of MRGN was 1.32 per 1,000 patient days. This rate is more than doubled the acquisition rates of other MDRO under surveillance within MDRO-KISS (0.57 MRSA, 0.49 VRE). CRO-acquisition rate was 0.3 per 1,000 patient days. Incidence density of MRGN infections bacteria was 0.58 per 1,000 patient days (CRO 0.15/1,000 patient days). CONCLUSIONS: To date, CRO are common in German ICUs and the relatively large proportions of ICU-acquired CRO and infections emphasize their potential to cause outbreaks. High MRGN infection rates and high ESBL prevalence data from clinical studies suggest a lack of MRGN identification in asymptomatic carriers.

New hosts for the mite Ornithonyssus bursa in Argentina.

The mite Ornithonyssus bursa (Berlese) (Mesostigmata: Macronyssidae) is considered a poultry pest causing important infestations in chickens and it is considered a potential vector of arbovirus. Despite being considered a common parasite in wild birds, there is scarce published information about its potential hosts and effects on them. Here we present new bird hosts for O. bursa, assess the presence of Alphavirus, Flavivirus and Bunyavirus in mites from three host species, and discuss its potential impact on wild bird populations. We found O. bursa infecting five raptor and six passerine wild bird species. For nine of these species, this is the first record of infection by O. bursa. Although all analysed mites were negative for the examined arboviruses, the small sample size of mites does not allow further conclusions at the present moment. Because of the general nature of this ectoparasite, its presence in migratory long dispersal and endangered bird species, and the seropositivity for arboviruses in some of the species studied here, we consider it critical to assess the role of O. bursa and other ectoparasites as vectors and reservoirs of pathogens and as potential deleterious agents in wild bird populations.

Detection of Orthobunyavirus in mosquitoes collected in Argentina.

Bunyamwera virus (BUNV) (Bunyaviridae, genus Orthobunyavirus, serogroup Bunyamwera) is considered an emerging pathogen for humans and animals in American countries. The CbaAr-426 strain of BUNV was recovered from mosquitoes Ochlerotatus albifasciatus (Diptera: Culicidae) collected in Córdoba province (Argentina), where serological studies detected high seroprevalences in humans and animals. Molecular detection of Orthobunyavirus was performed in mosquitoes collected in Córdoba province. Seventeen mosquito pools of Oc. albifasciatus, Ochlerotatus scapularis and Culex quinquefasciatus (Diptera: Culicidae) showed positive results; four of these positive pools, all of Oc. scapularis, were sequenced. All amplicons grouped with BUNV in the Bunyamwera serogroup. The findings highlight the circulation of BUNV in Córdoba province and represent the first report of BUNV-infected Oc. scapularis mosquitoes in Argentina.

Gastrointestinal ostomies and sexual outcomes: a comparison of colorectal cancer patients by ostomy status.

PURPOSE: Research examining effects of ostomy use on sexual outcomes is limited. Patients with colorectal cancer were compared on sexual outcomes and body image based on ostomy status (never, past, and current ostomy). Differences in depression were also examined. METHODS: Patients were prospectively recruited during clinic visits and by tumor registry mailings. Patients with colorectal cancer (N = 141; 18 past ostomy; 25 current ostomy; and 98 no ostomy history) completed surveys assessing sexual outcomes (medical impact on sexual function, Female Sexual Function Index, International Index of Erectile Function), body image distress (Body Image Scale), and depressive symptoms (Center for Epidemiologic Studies Depression Scale-Short Form). Clinical information was obtained through patient validated self-report measures and medical records. RESULTS: Most participants reported sexual function in the dysfunctional range using established cut-off scores. In analyses adjusting for demographic and medical covariates and depression, significant group differences were found for ostomy status on impact on sexual function (p < .001), female sexual function (p = .01), and body image (p < .001). The current and past ostomy groups reported worse impact on sexual function than those who never had an ostomy (p < .001); similar differences were found for female sexual function. The current ostomy group reported worse body image distress than those who never had an ostomy (p < .001). No differences were found across the groups for depressive symptoms (p = .33) or male sexual or erectile function (p values ≥ .59). CONCLUSIONS: Colorectal cancer treatment puts patients at risk for sexual difficulties and some difficulties may be more pronounced for patients with ostomies as part of their treatment. Clinical information and support should be offered.

E-cadherin autoantibody profile in patients with pemphigus vulgaris.

BACKGROUND: Pemphigus vulgaris (PV) is an autoimmune skin blistering disease. The main targets of autoantibodies are the desmosomal proteins desmoglein (Dsg)3 and Dsg1. Anti-E-cadherin antibody is the second most frequent antibody found in pemphigus foliaceus (fogo selvagem), but the frequency in PV is unknown. OBJECTIVES: To determine the anti-E-cadherin antibody profile in the two major subtypes of PV: mucosal PV (mPV) and mucocutaneous PV (mcPV). METHODS: Sera from 80 patients with PV and 80 controls were tested. Patients with PV were subdivided into mPV (n = 18) and mcPV (n = 62). Samples were tested by E-cadherin, Dsg1 and Dsg3 enzyme-linked immunosorbent assays (ELISAs), and immunoprecipitation coupled with Western blotting (IP-WB). RESULTS: Both mPV and mcPV sera have antibodies against E-cadherin as demonstrated by ELISA and IP-WB. Both subtypes of PV have low levels of anti-E-cadherin antibodies, but significantly higher levels than healthy controls by ELISA (P < 0·0001). No difference exists in antibody levels between subgroups (P = 0·82). By IP-WB, 78% of mcPV sera reacted to E-cadherin, vs. 33% of mPV sera tested. Correlation analysis suggests a moderate correlation between anti-E-cadherin antibodies and Dsg1 antibodies (average r = 0·61), but no correlation with Dsg3 antibodies (average r = 0·19). Patients with mPV can have lower levels of Dsg1 antibodies compared with controls by ELISA (P < 0·0001). A few mPV sera also reacted to Dsg1 protein by IP-WB (17%). CONCLUSIONS: Anti-E-cadherin antibodies are present in both major subtypes of PV. A moderate correlation exists between E-cadherin and Dsg1 antibodies. Patients with mPV can have low levels of both E-cadherin and Dsg1 antibodies.

Analysis of transmission-related third-generation cephalosporin-resistant Enterobacterales by electronic data mining and core genome multi-locus sequence typing.

BACKGROUND: To contain intra-hospital transmission of third-generation cephalosporin-resistant Enterobacterales (3GCR-E), contact isolation precautions are recommended. AIM: To quantify transmissions of 3GCR Escherichia coli and 3GCR Klebsiella pneumoniae within a hospital. METHODS: An automated outbreak detection system (AODS) was used to identify clusters (N≥2) of 3GCR Enterobacterales for the years 2016, 2018 and 2020. Clusters were defined by phenotypic agreement of microbiological results and spatial and temporal relationship. Core genome multi-locus sequence typing (cgMLST) was used to confirm whether the cluster isolates were transmitted between patients. FINDINGS: A total of 4343 3GCR E. coli and 1377 K. pneumoniae isolates were analysed. Among the 3GCR E. coli isolates, the AODS identified 304 isolates as cluster isolates, the median cluster size was two (range: 2-5). The cgMLST analysis revealed that a total of 23 (7.5%) 3GCR E. coli cluster isolates were transmission-associated, of which 20 isolates (87%) were detected in intensive care patients. Among the 3GCR K. pneumoniae isolates, the AODS identified 73 isolates as cluster isolates, the median cluster size was two (range: 2-4). CgMLST revealed that 35 (48%) 3GCR K. pneumoniae cluster isolates were transmission associated, of which 27 isolates (77%) were detected in intensive care patients. CONCLUSION: For 3GCR K. pneumoniae, cgMLST confirmed the AODS results more frequently than for 3GCR E. coli. Therefore, contact isolation precautions for 3GCR K. pneumoniae may be appropriate on intensive care units, but only in certain circumstances, such as outbreaks, for Enterobacterales with lower transmissibility, such as E. coli.

Diabetes mellitus: Lessons from COVID-19 for monkeypox infection.

BACKGROUND AND AIMS: Type 2 Diabetes Mellitus is known to be linked to malfunctioning antiviral defense; however, its association with the severity of monkeypox is poorly understood. In this review, we discuss key immunological mechanisms in the antiviral response affected by poor glucose control that could impact the susceptibility and severity of monkeypox infection, leading to a heightened emphasis on the use of the available antidiabetic drugs. METHODS: We searched PubMed and Google scholar for articles published from January 1985 to August 2022. No criteria for publication data were set, and all articles in English were included. RESULTS: Currently, there are no studies about the risk or consequences of monkeypox infection in the diabetic population. A high incidence of diabetes is reported in countries such as China, India, Pakistan, EUA, Indonesia, Brazil, Mexico, Bangladesh, Japan, and Egypt, where unfortunately imported cases of monkeypox have been reported and the infection continues to spread. CONCLUSIONS: High incidence of diabetes together with the cessation of smallpox vaccination has left large numbers of the human population unprotected against monkeypox. The best option for the population remains confined to the prevention of infection as well as the use of hypoglycemic agents that have also been shown to improve immune mechanisms associated with viral protection.

Encoding signs of orofacial neuropathic pain from facial expressions in mice.

OBJECTIVE: To evaluate the effects of mental nerve injury in the facial reactions elicited by mechanical stimulation of different intensities and detect and quantify spontaneous facial pain-like expressions during a period free of stimuli, as signs of evoked and spontaneous pain in a mouse model for neuropathic orofacial pain. DESIGN: We recorded mouse heads in a fixed position during a stimulus-free period and with mechanical stimulation with 3 different Von Frey filaments. We extracted the Histograms of Oriented Gradients of each frame of the video recordings to be compared with a prototypical pain-like facial expression. The similarity score was then used to register and quantify the percentage of spontaneous pain-like facial reactions and evaluate the increased similarity to the prototypical pain-like face evoked by mechanical stimuli. The assessments were made one day before and four days after a unilateral mental nerve compression. RESULTS: Our findings show that mental nerve injury promotes an increase in spontaneous facial pain-like expressions and reduced mechanical threshold, reflected in a higher similarity to our pain-like face prototype, regardless of the intensity of the stimuli applied. CONCLUSIONS: Machine vision encodes the facial expression associated with evoked and spontaneous pain after mental nerve injury for up to four days. Facial expression quantitatively reflects the increased mechanical sensitivity elicited by mental nerve injury. We also show that this technique can detect spontaneous pain-like responses from facial reactions. Artificial vision can be applied to evaluate signs of orofacial neuropathic pain to study the involved neural circuits.

Next-Generation Liquid Biopsies: Embracing Data Science in Oncology.

Deeper and broader sequencing of circulating tumor DNA (ctDNA) has identified a wealth of cancer markers in the circulation, resulting in a paradigm shift towards data science-driven liquid biopsies in oncology. Although panel sequencing for actionable mutations in plasma is moving towards the clinic, the next generation of liquid biopsies is increasingly shifting from analyzing digital mutation signals towards analog signals, requiring a greater role for machine learning. Concomitantly, there is an increasing acceptance that these cancer signals do not have to arise from the tumor itself. In this Opinion, we discuss the opportunities and challenges arising from increasingly complex cancer liquid biopsy data.

Beta2-microglobulin-deficient mice are resistant to bullous pemphigoid.

Recent understanding of the mechanism of immunoglobulin G (IgG) catabolism has yielded new insight into antibody-mediated diseases. We proposed that beta2-microglobulin (beta2m)-deficient mice have been protected from systemic lupus erythematosis (SLE)-like syndromes because they lack the beta2m-associated IgG protection receptor (FcRn) and therefore catabolize IgG, including pathogenic IgG autoantibodies, considerably more rapidly than normal mice. Such an hypothesis would predict that beta2m-deficient mice would also be resistant to experimental bullous pemphigoid, a disease with a pathogenesis thought to be much simpler than SLE, being the result of antibody directed toward a pathogenic epitope on the epidermal hemidesmosome that anchors basal keratinocytes to the basement membrane. To test this hypothesis, we administered pathogenic rabbit antibody directed toward the hemidesmosome to beta2m-deficient mice and to normal control mice, both intraperitoneally and intradermally, and assessed the mice clinically, histologically, and immunologically for manifestations of skin disease. We found that the beta2m-deficient mice were protected when the antibody was given intraperitoneally whereas intradermal administration resulted in blisters only slightly less severe than those seen in normal mice. These data would indicate that autoantibody-mediated inflammation might be prevented or controlled by appropriate modulation of FcRn function.

Gelatinase B-deficient mice are resistant to experimental bullous pemphigoid.

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease characterized by deposition of autoantibodies at the basement membrane zone. In an experimental BP model in mice, the subepidermal blistering is mediated by antibodies directed against the hemidesmosomal protein BP180 (collagen XVII, BPAG2), and depends on complement activation and neutrophil infiltration. Gelatinase B is present in BP blister fluid and can cleave BP180. In this study we investigated the role of gelatinase B in the immunopathogenesis of experimental BP using mice containing targeted disruption of the gelatinase B (MMP-9, 92 kD gelatinase) gene. Gelatinase B-deficient mice were resistant to the blistering effect of intracutaneous anti-mBP180 antibodies, although these mice showed deposition of autoantibodies at the basement membrane zone and neutrophil recruitment to the skin comparable to that observed in the control mice. Interleukin 8 given intradermally concomitantly with pathogenic anti-mBP180 elicited a significant neutrophil recruitment into the skin in gelatinase B-deficient mice, but blistering did not occur. However, gelatinase B-deficient mice reconstituted with neutrophils from normal mice developed blistering in response to anti-mBP180 antibodies. These results implicate neutrophil-derived gelatinase B in the pathogenesis of experimental BP and might lead to novel therapeutic strategies for BP.

Cocirculation of Rio Negro Virus (RNV) and Pixuna Virus (PIXV) in Tucumán province, Argentina.

Venezuelan equine encephalitis complex includes viruses considered emerging pathogens for humans and animals in the Americas. Two members of this complex have been detected previously in Argentina: Rio Negro Virus (RNV), detected in mosquitoes from Chaco province and rodents from Formosa province, and Pixuna Virus (PIXV), detected in mosquitoes from Chaco province. To carry out surveillance studies in other parts of the country, detection of a 195-bp fragment of alphaviruses by RT-nested PCR was performed in mosquito samples from San Miguel de Tucumán city. Four pools resulted positive and three were sequenced. Two amplicons grouped with RNV and one with PIXV. This is the first report of viral activity of members of the Venezuelan equine encephalitis complex in north-eastern Argentina.