Beneath the surface: a case report on nonencapsulated Streptococcus pneumoniae-associated invasive disease in an immunocompromised patient.

Background: Streptococcus pneumoniae, a prominent human pathogen linked to various systemic diseases, includes non-typeable pneumococci marked by the absence of a detectable capsule. However, the majority of invasive infections are attributed to encapsulated strains. This case report details the first documented instance of invasive disease caused by non-typeable S. pneumoniae in Argentina since 2017. Case Presentation: A 19-year-old woman presented with haemorrhagic injuries attributed to chronic oral mucosa irritation. Subsequent hospitalization revealed bone marrow aplasia, leading to antibiotic, antifungal, antiviral, and immunosuppressive treatments, culminating in her discharge. Two weeks later, she was readmitted with sepsis related to a respiratory focus, exhibiting a negative COVID-PCR test. After ten days, ICU admission revealed additional infections: positive COVID-PCR test, fungal sinusitis, and S. pneumoniae bacteremia. Targeted treatments led to improvement, and the patient was subsequently discharged. S pneumoniae characterization: Verification of the capsule's absence utilized traditional methods such as the Quellung reaction, transmission electron microscopy, molecular assays, and Whole Genome Sequencing (WGS). The isolate, identified as ST18335, displayed genetic features and antibiotic resistance patterns, concordant between WGS and the agar dilution method. It demonstrated non-susceptibility to penicillin and cefotaxime, based on meningitis breakpoints, as well as meropenem and cotrimoxazole. Conclusion: This case underscores the clinical significance of non-typeable S. pneumoniae, emphasizing the necessity for a comprehensive approach to identification and characterization. The findings contribute to ongoing discussions regarding the challenges posed by non-typeable strains in vaccine development, understanding clinical impacts, and addressing antibiotic resistance. As the pneumococcal epidemiological landscape evolves, this case serves as a valuable addition to the evolving knowledge surrounding non-typeable S. pneumoniae, highlighting the continued need for surveillance and research in infectious diseases.

Symptomatic Patient With Two Separate Accessory Navicular Bones.

We present the case of a symptomatic patient with two separate accessory navicular bones, a novel finding that does not fall within current classification standards. Furthermore, there is a paucity of current literature with regard to the management of symptomatic cases. Accessory navicular bones, sometimes referred to as os naviculare, are ossicles that can occur in multiple configurations and are considered developmental anomalies. The accessory navicular is an accessory bone found on the medial side of the navicular bone of the foot. While often asymptomatic, they can occasionally lead to clinically significant pain and/or deformity that can cause patients to seek out treatment and sometimes surgical correction. Diagnosis relies on clinical suspicion and imaging studies. A nine-year-old female patient presented initially with complaints of sharp pain over the medial side of her left foot, after which X-rays were obtained that demonstrated an accessory navicular bone. Upon diagnosis, conservative measures were implemented, including placing the patient in a short-leg cast with limited activity. After a failed trial of conservative measures, the patient underwent surgical excision of the accessory navicular bone, with imaging and intraoperative findings of two separate accessory navicular bones, a unique finding in patients with accessory navicular bones. During the six-week follow-up, the patient improved with no new complaints or concerns and was informed she could begin weight-bearing as tolerated with two crutches; she was then weaned from the crutches and returned to normal activity. In the current case, we followed the same route of treatment used to treat a single accessory navicular bone, utilizing first non-surgical interventions and then ultimately surgical excision after continual pain despite conservative measures. This case highlights the promising outcome for a patient with two separate accessory navicular bones when following the guidelines for the treatment of a single accessory navicular bone.

Pediatric Medial Condyle of Humerus Fracture Dislocation: A Case Report.

We present the case of a six-year-old male patient, status post fall with elbow dislocation, successfully reduced. At the time of injury, he had normal appearing x-rays, signs of a mildly discrete chip, and possible epicondyle ossification, but no definitive fracture. A medial condyle fracture with dislocation was missed at the original time of injury. The patient returned several years later with mild elbow stiffness and intermittent pain. CT scan at this time demonstrated nonunion of the medial condyle. The patient underwent subsequent open reduction and internal fixation (ORIF) and is currently doing well clinically. Although rare, a medial condyle dislocation fracture needs surgical intervention to reduce morbidity, and therefore, should be in the differential when working up a pediatric fracture.

Design and Validation of a Test to Evaluate the Execution Time and Decision-Making in Technical-Tactical Football Actions (Passing and Driving).

Reaction time and decision-making (DMA) in football have usually been evaluated using edited images or videos of game situations. The purpose of this research is to design and validate a test that simultaneously evaluates execution time (ET) and decision-making (DMA) in the subcategories of type of action (TA) and direction of movement (DM). METHODOLOGY: A quantitative, cross-sectional, and descriptive study of 30 young players. A total of 32 stimuli were programmed, corresponding to 64 responses, from which the total index (TI) was obtained from the division between DMA and ET. RESULTS: The content validity index (CVI = 0.78) showed a high degree of consensus among experts. In the validation process, the intraclass correlation coefficient (ICC) was used to assess intraclass and interobserver reliability, and a moderate level of agreement was found between subjects for the TA (ICC = 0.593) and ET (ICC = 0.602) and a moderate high level of concordance for DM (ICC = 0.804) and TI (ICC = 0.855). Regarding interobserver reliability, an excellent level of agreement was found for all variables: TA (ICC = 0.998), DM (ICC = 0.998), ET (ICC = 1.000), and TI (ICC = 1.000). For the relationship between intraobserver and interobserver variables, statistical significance was established as p < 0.01. Finally, the intraobserver ETM (5.40%) and interobserver ETM (0.42%) was low compared with the reference value (5.9%). CONCLUSION: The designed test meets the validity criteria since the variables show sufficient intraclass reliability (test-retest) and reliability among observers.

Introduction and Differential Diagnosis of Monkeypox in Argentina, 2022.

We report detection of cases of monkeypox virus infection in Argentina in the context of a marked increase in confounding cases of atypical hand-foot-and-mouth syndrome caused by enterovirus coxsackie A6. We recommend performing an accurate differential virological diagnosis for exanthematous disease in suspected monkeypox cases.

MICA-Expressing Monocytes Enhance Natural Killer Cell Fc Receptor-Mediated Antitumor Functions.

Natural killer (NK) cells are large granular lymphocytes that promote the antitumor response via communication with other cell types in the tumor microenvironment. Previously, we have shown that NK cells secrete a profile of immune stimulatory factors (e.g., IFNγ, MIP-1α, and TNFα) in response to dual stimulation with the combination of antibody (Ab)-coated tumor cells and cytokines, such as IL12. We now demonstrate that this response is enhanced in the presence of autologous monocytes. Monocyte enhancement of NK cell activity was dependent on cell-to-cell contact as determined by a Transwell assay. It was hypothesized that NK cell effector functions against Ab-coated tumor cells were enhanced via binding of MICA on monocytes to NK cell NKG2D receptors. Strategies to block MICA-NKG2D interactions resulted in reductions in IFNγ production. Depletion of monocytes in vivo resulted in decreased IFNγ production by murine NK cells upon exposure to Ab-coated tumor cells. In mice receiving trastuzumab and IL12 therapy, monocyte depletion resulted in significantly greater tumor growth in comparison to mock-depleted controls (P < 0.05). These data suggest that NK cell-monocyte interactions enhance NK cell antitumor activity in the setting of monoclonal Ab therapy for cancer. Cancer Immunol Res; 5(9); 778-89. ©2017 AACR.

Modelling malaria elimination on the internet.

BACKGROUND: Unprecedented efforts are underway to eliminate malaria. Mathematical modelling can help to determine the optimal strategies for malaria elimination in different epidemiological settings. This is necessary as there is limited scope for expensive and time-consuming field studies and failure of planned elimination strategies is likely to discourage ongoing investment by funders. However, there has been very little modelling of malaria elimination and little direct involvement of policymakers in its development. There is thus an urgent need for user-friendly and accessible models purpose-designed in collaboration with policymakers to answer pertinent questions arising from the field. RESULTS: An internet site is presented with a simple mathematical modelling platform for population level models of malaria elimination. It is freely accessible to all and designed to be flexible so both the platform and models can be developed through interaction with users. The site is an accessible introduction to modelling for a non-mathematical audience, and lessons learned from the project will help inform future development of mathematical models and improve communication of modelling results. Currently it hosts a simple model of strategies for malaria elimination and this will be developed, and more models added, over time. The iterative process of feedback and development will result in an educational and planning tool for non-modellers to assist with malaria elimination efforts worldwide. CONCLUSIONS: By collaboration with end users, iterative development of mathematical models of malaria elimination through this internet platform will maximize its potential as an educational and public health policy planning tool. It will also assist with preliminary optimisation of local malaria elimination strategies before commitment of valuable resources.

IFN-alpha and bortezomib overcome Bcl-2 and Mcl-1 overexpression in melanoma cells by stimulating the extrinsic pathway of apoptosis.

We hypothesized that IFN-alpha would enhance the apoptotic activity of bortezomib on melanoma cells. Combined treatment with bortezomib and IFN-alpha induced synergistic apoptosis in melanoma and other solid tumor cell lines. Apoptosis was associated with processing of procaspase-3, procaspase-7, procaspase-8, and procaspase-9 and with cleavage of Bid and poly(ADP-ribose) polymerase. Bortezomib plus IFN-alpha was effective at inducing apoptosis in melanoma cells that overexpressed Bcl-2 or Mcl-1, suggesting that this treatment combination can overcome mitochondrial pathways of cell survival and resistance to apoptosis. The proapoptotic effects of this treatment combination were abrogated by a caspase-8 inhibitor, led to increased association of Fas and FADD before the onset of cell death, and were significantly reduced in cells transfected with a dominant-negative FADD construct or small interfering RNA targeting Fas. These data suggest that bortezomib and IFN-alpha act through the extrinsic pathway of apoptosis via FADD-induced caspase-8 activation to initiate cell death. Finally, bortezomib and IFN-alpha displayed statistically significant antitumor activity compared with either agent alone in both the B16 murine model of melanoma and in athymic mice bearing human A375 xenografts. These data support the future clinical development of bortezomib and IFN-alpha for malignant melanoma.

[Severe acute respiratory syndrome. The public health laboratory in a global emergency]. / Síndrome respiratorio agudo grave. El laboratorio de salud pública frente a una emergencia global.

By the end of year 2002 there was an outbreak of atypical pneumonia in Southeast Asia which soon spread to other continents. This new severe acute respiratory syndrome (SARS) was produced by a novel coronavirus. Due to the severity of the situation and risk of introduction of this pathology in our country, the need to arrange specific laboratory diagnostic tests arose. Classic techniques, such as the electron microscopy and molecular biology test such as retrotranscription followed by the polymerase chain reaction (RT-PCR) were implemented. The araldit included cells infected with bovine coronavirus which allowed the viral particles to be visualized easily but it took more time in comparison with the negative staining of free particles from viral cultures. RT-PCR was able to detect RNA of isolated viruses from cases in Hong Kong and Germany.

Síndrome respiratorio agudo grave. El laboratorio de salud pública frente a una emergencia global. / [Severe acute respiratory syndrome. The public health laboratory in a global emergency]

By the end of year 2002 there was an outbreak of atypical pneumonia in Southeast Asia which soon spread to other continents. This new severe acute respiratory syndrome (SARS) was produced by a novel coronavirus. Due to the severity of the situation and risk of introduction of this pathology in our country, the need to arrange specific laboratory diagnostic tests arose. Classic techniques, such as the electron microscopy and molecular biology test such as retrotranscription followed by the polymerase chain reaction (RT-PCR) were implemented. The araldit included cells infected with bovine coronavirus which allowed the viral particles to be visualized easily but it took more time in comparison with the negative staining of free particles from viral cultures. RT-PCR was able to detect RNA of isolated viruses from cases in Hong Kong and Germany.

A phase I study of interleukin 12 with trastuzumab in patients with human epidermal growth factor receptor-2-overexpressing malignancies: analysis of sustained interferon gamma production in a subset of patients.

PURPOSE: On the basis of preclinical studies, we hypothesized that interleukin (IL)12 would potentiate the antitumor actions of an antihuman epidermal growth factor receptor-2 (HER2) monoclonal antibody (trastuzumab). We conducted a Phase I trial to determine the safety and optimal biological dose of IL-12 when given in combination with trastuzumab. PATIENTS AND METHODS: Patients with metastatic HER2-positive malignancies received trastuzumab on day 1 of each weekly cycle. Beginning in week 3, patients also received intravenous injections of IL-12 on days 2 and 5. The IL-12 component was dose-escalated within cohorts of 3 patients (30, 100, 300, or 500 ng/kg). Correlative assays were conducted using serum samples and peripheral blood cells obtained during the course of therapy. RESULTS: Fifteen patients were treated, including 12 with HER2 2+ or 3+ breast cancer. The regimen was well tolerated with IL-12-induced grade 1 nausea and grade 2 fatigue predominating. Evaluation of dose-limiting toxicity and biological end points suggested that the 300 ng/kg dose was both the maximally tolerated dose and the optimal biological dose of IL-12 for use in combination with trastuzumab. Two patients with HER2 3+ breast cancer within the 500 ng/kg dose level experienced grade 1 asymptomatic decreases in left ventricular ejection fraction of 12% and 19% after 3 and 10 months of therapy, respectively. There was one complete response in a patient with HER2 3+ breast cancer metastatic to the axillary, mediastinal, and supraclavicular nodes, and 2 patients with stabilization of bone disease lasting 10 months and >12 months, respectively. Correlative assays showed sustained production of interferon (IFN)gamma by natural killer cells only in those patients experiencing a clinical response or stabilization of disease. Elevated serum levels of macrophage inflammatory protein-1alpha, tumor necrosis factor-alpha, and the antiangiogenic factors IFN-gamma inducible protein-10 and monokine induced by gamma were also observed in these patients. Patient genotyping suggested that a specific IFN-gamma gene polymorphism might have been associated with increased IFN-gamma production. The ability of patient peripheral blood cells to conduct antibody-dependent cellular cytotoxicity against tumor targets in vitro did not correlate with clinical response or dose of IL-12. CONCLUSIONS: The addition of IL-12 to trastuzumab therapy did not appear to enhance the efficacy of this antibody treatment. Sustained production of IFN-gamma and other cytokines were observed in three patients: One who exhibited a complete response and two others who had stabilization of disease lasting over 6 months. Given the small sample size and heterogeneity of the patient population, the effects of IL-12 on the innate immune response to trastuzumab therapy should be further explored in the context of a larger clinical trial.