Acute Phase Research Articles

Possible alteration in serum ferritin level in malaria infected HIV seropositive individuals in Nauth, Nnewi, Nigeria

The role of Ferritin in monitoring disease progression in immune compromised HIV individuals with an underlying active infection like malaria is a subject of growing research. Ferritin being an acute phase protein, plays important role in assessing the range of damage due to inflammation in immunosuppressed patients leaving in highly endemic malaria regions. The levels of serum ferritin in malaria infected HIV positive individuals in Nnamdi Azikiwe University teaching hospital (NAUTH), Nnewi, Anambra State, Nigeria, was assessed. Questionnaire was used to obtain the demographic details of the participants, and to rule out other inflammatory infections. 88 participants of the age group 18 - 65 years, comprising 24 with HIV infection, 22 with HIV and Malaria co-infection, 22 with Malaria infection, and a control group of 22 individuals with neither HIV nor malaria infection were randomly recruited. Ferritin level was determined using enzyme linked immunosorbent assay technique and a cross sectional prospective study design was used. A significantly high mean serum ferritin level was observed in HIV infected individuals with and/ or without malaria co-infection than in malaria positive and control group (p<0.05 respectively). Serum ferritin level was significantly higher in female participants than in male counterparts (p < 0.05). Serum ferritin level was significantly higher in individuals with CD4 count >500 than in CD4 count ≤ 500 (p < 0.05). Blood pressure was significantly higher in HIV infected and malaria positive individuals when compared with controls. The increased serum ferritin level and higher blood pressure in HIV infected participants suggests active inflammatory process, reduced immunity and hypertension which may have worsened by malaria co-infection. This may subsequently lead to vascular and endothelia damage causing disease severity.

Neuralgic Amyotrophy: A Commonly Overlooked Cause of Acute Shoulder Pain.

Neuralgic amyotrophy (NA) is a multifactorial, monophasic neuritis that mainly affects the nerves of the shoulder girdle. It is characterized by very severe pain and by weakness that arises some time after the pain. Its reported incidence is high (100 cases per 100 000 persons per year), but our data suggest that many or most cases are diagnosed late or not at all. This review of the epidemiology, pathophysiology, diagnosis, and treatment of NA is based on pertinent publications retrieved by a selective literature search, and on data provided by the scientific institute of AOK, a German statutory health-insurance carrier. It is currently thought that the combination of a genetic predisposition, an immunological trigger factor, and mechanical stress on the affected nerve segment(s) is pathophysiologically determinative. The prognosis of untreated NA is poor, with 25% of patients remaining unable to work at three years. The main form of treatment is with corticosteroids that are administered as early as possible. If there is evidence of nerve constriction or torsion, surgery may also help. There have only been six controlled cohort studies on the treatment of NA, and no randomized trials. It is not uncommon for the acute phase to develop into a chronic pain syndrome requiring multidimensional treatment. Particularly in view of the high incidence and improved therapeutic options, NA should be included in the differential diagnosis of all patients with suggestive symptoms.

Predictive value of the random forest model based on bioelectrical impedance analysis parameter trajectories for short-term prognosis in stroke patients

BackgroundThe short-term prognosis of stroke patients is mainly influenced by the severity of the primary disease at admission and the trend of disease development during the acute phase (1–7 days after admission).ObjectiveThe aim of this study is to explore the relationship between the bioelectrical impedance analysis (BIA) parameter trajectories during the acute phase of stroke patients and their short-term prognosis, and to investigate the predictive value of the prediction model constructed using BIA parameter trajectories and clinical indicators at admission for short-term prognosis in stroke patients.MethodsA total of 162 stroke patients were prospectively enrolled, and their clinical indicators at admission and BIA parameters during the first 1–7 days of admission were collected. A Group-Based Trajectory Model (GBTM) was employed to identify different subgroups of longitudinal trajectories of BIA parameters during the first 1–7 days of admission in stroke patients. The random forest algorithm was applied to screen BIA parameter trajectories and clinical indicators with predictive value, construct prediction models, and perform model comparisons. The outcome measure was the Modified Rankin Scale (mRS) score at discharge.ResultsPA in BIA parameters can be divided into four separate trajectory groups. The incidence of poor prognosis (mRS: 4–6) at discharge was significantly higher in the “Low PA Rapid Decline Group” (85.0%) than in the “High PA Stable Group “ (33.3%) and in the “Medium PA Slow Decline Group “(29.5%) (all P < 0.05). In-hospital mortality was the highest in the “Low PA Rapid Decline Group” (60%) compared with the remaining trajectory groups (P < 0.05). Compared with the prediction model with only clinical indicators (Model 1), the prediction model with PA trajectories (Model 2) demonstrated higher predictive accuracy and efficacy. The area under the receiver operating characteristic curve (AUC) of Model 2 was 0.909 [95% CI 0.863, 0.956], integrated discrimination improvement index (IDI), 0.035 (P < 0.001), and net reclassification improvement (NRI), 0.175 (P = 0.031).ConclusionPA trajectories during the first 1–7 days of admission are associated with the short-term prognosis of stroke patients. PA trajectories have additional value in predicting the short-term prognosis of stroke patients.

Unexpected arboviruses found in an epidemiological surveillance of acute tropical febrile syndrome in the department of Meta, Eastern Colombia

BackgroundNonspecific acute tropical febrile illnesses (NEATFI) are common in the Latin American tropics. Dengue, Chikungunya, Zika, Mayaro, and Usutu, among others, can coexist in the American tropics. This study aimed to surveil the arboviruses that cause| acute febrile syndrome in patients in the Meta department, Colombia. MethodsBetween June 2021 and February 2023, an epidemiological surveillance study was conducted in the Llanos of the Meta department in Eastern Colombia. ResultsOne hundred patients in the acute phase with typical prodromal symptoms of NEATFI infection who attended the emergency department of the Villavicencio Departmental Hospital were included. ELISA tests were performed for Dengue, Usutu, Chikungunya, and Mayaro. RT-qPCR was performed to detect the arboviruses Usutu, Dengue, Zika, Mayaro, and Oropouche. The seroprevalence for the Chikungunya, Mayaro, and Usutu viruses was 41% (28/68), 40% (27/67), and 62% (47/75), respectively. Seroconversion for Chikungunya was observed in one patient; two seroconverted to Mayaro and one to Usutu. The NS5 gene fragment of the Usutu virus was detected in nine febrile patients. RT-qPCR of the remaining arboviruses was negative. The clinical symptoms of the nine Usutu-positive patients were very similar to those of Dengue, Chikungunya, Zika, and Mayaro infections. ConclusionsThe pervasive detection of unexpected viruses such as Usutu and Mayaro demonstrated the importance of searching for other viruses different from Dengue. Because Usutu infection and Mayaro fever have clinical features like Dengue, a new algorithm should be proposed to improve the accuracy of acute tropical fevers.

The connections of sialic acids and diabetes mellitus: therapeutic or diagnostic value?

Modulation of sialic acids is one of the important pathological consequences of both type 1 and type 2 diabetes mellitus with or without the micro- and macrovascular complications. However, the mechanistic, therapeutic and/or diagnostic implications of these observations are uncoordinated and possibly conflicting. This review critically analyses the scientific investigations connecting sialic acids with diabetes mellitus. Generally, variations in the levels and patterns of sialylation, fucosylation and galactosylation were predominant across various tissues and body systems of diabetic patients, but the immune system seemed to be most affected. These might be explored as a basis for differential diagnosis of various diabetic complications. Sialic acids are predominantly elevated in nearly all forms of diabetic conditions, particularly nephropathy and retinopathy, which suggests some diagnostic value but the mechanistic details were not unequivocal from the available data. The plausible mechanistic explanations for the elevated sialic acids are increased desialylation by sialidases, stimulation of hexosamine pathway and synthesis of acute phase proteins as well as oxidative stress. Additionally, sialic acids are also profoundly associated with glucose transport and insulin resistance in human-based studies while animal-based studies revealed that the increased desialylation of insulin receptors by sialidases, especially NEU1, might be the causal link. Interestingly, inhibition of the diabetes-associated NEU1 desialylation was beneficial in diabetes management and might be considered as a therapeutic target. It is hoped that the article will provide an informed basis for future research activities on the exploitation of sialic acids and glycobiology for therapeutic and/or diagnostic purposes against diabetes mellitus.

Flow augmentation therapies preserve brain network integrity and hemodynamics in a canine permanent occlusion model

The acute phase of ischemic stroke presents a critical window for therapeutic intervention, where novel approaches such as hyper-acute cerebral flow augmentation offer promising avenues for neuroprotection. In this study, we investigated the effects of two such therapies, NEH (a combination of norepinephrine and hydralazine) and Sanguinate (pegylated bovine carboxyhemoglobin), on resting-state functional connectivity, global mean signal (GMS), and blood oxygen level-dependent (BOLD) time lag in a pre-clinical canine model of stroke via permanent occlusion of the middle cerebral artery (total of n = 40 IACUC-approved mongrel canines randomly split into control/natural history and two treatment groups). Utilizing group independent component analysis (ICA), we identified and examined the integrity of sensorimotor and visual networks both pre- and post-occlusion, across treatment and control groups. Our results demonstrated that while the control group exhibited significant disruptions in these networks following stroke, the treatment groups showed remarkable preservation of network integrity. Voxel-wise functional connectivity analysis revealed less pronounced alterations in the treatment groups, suggesting maintained neural connections. Notably, the treatments stabilized GMS, with only minimal reductions observed post-occlusion compared to significant decreases in the control group. Furthermore, BOLD time-lag unity plots indicated that NEH and Sanguinate maintained consistent hemodynamic response timing, as evidenced by tighter clustering around the line of unity, suggesting a potential neuroprotective effect. These findings were underscored by robust statistical analyses, including paired T-tests and Mann–Whitney U tests, which confirmed the significance of the connectivity changes observed. The correlation of BOLD time-lag variations with neuroimaging functional biomarkers highlighted the impact of stroke and the efficacy of early therapeutic interventions. Our study supports the further study of flow augmentation therapies such as NEH and Sanguinate in stroke treatment protocols and suggests flow augmentation therapies should be further explored in an effort to improve patient outcomes.

The Hand, Foot, and Mouth Disease Sentinel Surveillance System in South Korea: Retrospective Evaluation Study.

South Korea has implemented a hand, foot, and mouth disease (HFMD) surveillance system since 2009 to monitor incidence trends and identify disease burden. This nationwide surveillance involves a network of approximately 100 pediatric clinics that report all probable and confirmed HFMD cases. Following the COVID-19 pandemic, infectious disease surveillance systems must be evaluated to ensure the effective use of limited public health resources. This study aimed to evaluate the HFMD sentinel surveillance system in South Korea from 2017 to 2022, focusing on the transition period after the COVID-19 pandemic. We retrospectively reviewed the HFMD sentinel surveillance system from the Korea Disease Control and Prevention Agency using systematic guidelines for public health surveillance system evaluation developed by the US Centers for Disease Control and Prevention. We assessed the system's overall performance in 5 main factors: timeliness, stability, completeness, sensitivity, and representativeness (ie, the age and geographic distribution of sentinels). We rated these factors as weak, moderate, or good. Our study showed that the completeness, sensitivity, and age representativeness of the HFMD surveillance performance were temporarily reduced to moderate levels from 2020 to 2021 and recovered in 2022, while the timeliness and geographic representativeness were maintained at a good level throughout the study period. The stability of the surveillance was moderate from 2017 to 2021 and weak in 2022. This is the first study to evaluate the HFMD surveillance system after the acute phase of the COVID-19 pandemic. We identified a temporarily reduced level of performance (ie, completeness, sensitivity, and age-specific representativeness) during the acute phase of the pandemic and good performance in 2022. Surveillance system evaluation and maintenance during public health emergencies will provide robust and reliable data to support public health policy development. Regular staff training programs and reducing staff turnover will improve HFMD surveillance system stability.

Vasa vasorum enhancement on optical coherence tomography in Kawasaki disease.

Patients with Kawasaki disease (KD) prone to develop coronary artery aneurysm (CAA) with unknown etiology. We aimed to disclose the relationship between vasa vasorum (VV) and intimal thickening using optical coherence tomography (OCT) in KD. Forty-three coronary artery branches of 21 patients with KD were examined by OCT. The coronary arteries were classified into three groups: the CAA group (n = 9) in which CAAs remained since the acute phase, the regressed group (n = 16) in which CAAs were regressed, and the no CAA group (n = 18). The number and distribution of VV, and intimal thickening in coronary arteries were evaluated on OCT. Intimal thickening was significantly more severe in the CAA and regressed groups than in the no CAA group (median: 481, 474, and 218 μm, p = 0.001 and p < 0.001, respectively). The number of VV in the regressed group was significantly higher than that in the CAA and no CAA groups. The numbers of adventitial VV and internal VV were positively correlated with the intimal thickness (R = 0.64, p < 0.001; R = 0.62, p < 0.001, respectively). In the no CAA group, no internal VV were observed. VV enhances according to intimal thickening, suggesting that VV may have some link to the healing process, such as CAA regression and intimal thickening. Kawasaki disease (KD) is a vasculitis syndrome developing coronary artery aneurysm, however its etiology still remains unclear. Coronary artery imaging using optical coherence tomography (OCT) can reveal coronary arterial wall pathology, however OCT studies are limited in patients with KD. Using OCT, we disclosed the closed relationship between vasa vasorum enhancement and regressed coronary arterial lesions. Vasa vasorum enhancement is involved in the pathomechanism of the convalescent phase of KD.

Transcriptomic Signatures of Zika Virus Infection in Patients and a Cell Culture Model

Zika virus (ZIKV), a re-emerging flavivirus, is associated with devasting developmental and neurological disease outcomes particularly in infants infected in utero. Towards understanding the molecular underpinnings of the unique ZIKV disease pathologies, numerous transcriptome-wide studies have been undertaken. Notably, these studies have overlooked the assimilation of RNA-seq analysis from ZIKV-infected patients with cell culture model systems. In this study we find that ZIKV-infection of human lung adenocarcinoma A549 cells, mirrored both the transcriptional and alternative splicing profiles from previously published RNA-seq data of peripheral blood mononuclear cells collected from pediatric patients during early acute, late acute, and convalescent phases of ZIKV infection. Our analyses show that ZIKV infection in cultured cells correlates with transcriptional changes in patients, while the overlap in alternative splicing profiles was not as extensive. Overall, our data indicate that cell culture model systems support dissection of select molecular changes detected in patients and establishes the groundwork for future studies elucidating the biological implications of alternative splicing during ZIKV infection.

Effects of fasudil on glial cell activation induced by tooth movement

BackgroundOrthodontic pain affects the physical and mental health of patients. The spinal trigeminal subnucleus caudalis (SPVC) contributes to the transmission of pain information and serves as a relay station for integrating orofacial damage information. Recently, glial cells have been found to be crucial for both acute and maintenance phases of pain. It has also been demonstrated that rho kinase (ROCK) inhibitors can manage different pain models by inhibiting glial cell activation. Here, we hypothesized that orthodontic pain is related to glial cells in the SPVC, and Fasudil, a representative rho/rock kinase inhibitor, can relieve orthodontic pain by regulating the function of glial cells and the related inflammatory factors. In this study, we constructed a rat model of tooth movement pain and used immunofluorescence staining to evaluate the activation of microglia and astrocytes. Quantitative real-time PCR was used to detect the release of related cytokines and the expression of pain-related genes in the SPVC. Simultaneously, we investigated the effect of Fasudil on the aforementioned indicators.ResultsIn the SPVC, the expression of c-Fos peaked on day 1 along with the expression of OX42 (related to microglial activation), CD16 (a pro-inflammatory factor), and CD206 (an anti-inflammatory factor) on day 3 after tooth movement, followed by a gradual decrease. GFAP-staining showed that the number of activated astrocytes was the highest on day 5 and that cell morphology became complex. After Fasudil treatment, the expression of these proteins showed a downward trend. The mRNA levels of pro-inflammatory factors (IL-1β and TNF-α) peaked on day 3, and the mRNA expression of the anti-inflammatory factor TGF-β was the lowest 3 days after tooth movement. Fasudil inhibited the mRNA expression of pain-related genes encoding CSF-1, t-PA, CTSS, and BDNF.ConclusionThis study shows that tooth movement can cause the activation of glial cells in SPVC, and ROCK inhibitor Fasudil can inhibit the activation of glial cells and reduce the expression of the related inflammatory factors. This study presents for the first time the potential application of Fasudil in othodontic pain.

Novel and characteristic radiological features of neurosyphilis: a case series

BackgroundTreponema pallidum can invade the central nervous system (CNS) early in its infection, causing neurosyphilis. Neurosyphilis typically presents with meningovasculitis in the acute or subacute phase, while tabes dorsalis and dementia paralytica are classical conditions in the later stages. However, syphilis is often misdiagnosed as other conditions such as tumors or autoimmune diseases including vasculitis and encephalitis, which is why the condition is known as “The Great Mimicker.” The increasing incidence of syphilis in recent years emphasizes the importance of early diagnosis and treatment; however, its multiple clinical manifestations impose diagnostic challenges for clinicians because it resembles other diseases. In this case series, we present the impressive manifestations of neurosyphilis through three unique radiological presentations.Case presentationCase 1 details optic nerve involvement in an HIV-positive male, where MRI and fundoscopic findings confirmed syphilitic optic neuritis. Case 2 describes a patient in her pregnancy initially suspected of acoustic neuroma on MRI, later diagnosed with syphilitic gumma affecting the inner ear canal. Case 3 is a young male with clinical features mimicking temporal arteritis, ultimately identified as skull osteomyelitis secondarily causing inflammation of the musculus temporalis and meningitis.ConclusionsThese cases underscore the necessity of considering syphilis in differential diagnoses, given the diversity of its clinical presentations. Radiology plays an important role in avoiding unnecessary interventions. The increasing prevalence of recurrent syphilis imposes diagnostic challenges, emphasizing the importance of the early diagnosis and treatment of neurosyphilis by clinicians.

Prolonged administration of the granisetron transdermal delivery system reduces capecitabine plus oxaliplatin regimen induced nausea and vomiting

ObjectiveTo evaluate the safety and efficacy of the granisetron transdermal delivery system (GTDS) combined with Dexamethasone for preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving Capecitabine plus Oxaliplatin (CapeOX) therapy.DesignOpen-label, prospective, multi-center phase II trial.SettingThree institutions.ParticipantsFifty-four patients scheduled to receive CapeOX chemotherapy.InterventionsParticipants received GTDS (3.1 mg applied to the upper arm 48 h before chemotherapy, replaced on day 5, and discarded on day 12) and Dexamethasone.Main outcome measuresThe primary endpoint was the complete control rate of CINV. Secondary endpoints included the duration of delayed complete control, complete control rate in the acute phase, safety, and quality of life.ResultsThe complete control rate for delayed CINV over the entire period (25–480 h) was 72.7% (95% CI 0.57–0.88). The duration of delayed complete control was 17.2 ± 4.5 days, with 51.5% of patients experiencing no nausea during the delayed phase. The complete control rate in the acute phase was 81.8% (95% CI 0.69–0.95). No serious adverse events related to the antiemetic regimen were reported.ConclusionProlonged administration of GTDS is safe and effective for preventing CINV in patients with gastrointestinal malignancies treated with CapeOX.Trial RegistrationClinicalTrials.gov registry (NCT05325190); registered on October 10, 2021.

Mannose-Binding Lectin Gene Variants as Disease Susceptibility Biomarkers in Rheumatoid Arthritis.

Background: Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease characterized by progressive destruction of peripheral joints. About 1% of the human population worldwide is suffering from this disease. The pathophysiology of RA is largely being influenced by immune dysregulation. Mannose-binding lectin (MBL), an acute-phase protein, has been reported to play an important role in pathogenesis of RA by the activation of complement pathway. Various studies documented the established the role of MBL in pathogenesis of various autoimmune diseases, including RA. MBL protein is encoded by gene MBL2, mapped on chromosome 10q11.2-q21. Objective: Both MBL serum levels and activity are mainly determined genetically by its variants. So considering the putative clinical role of MBL2, this case-control association study was designed to assess its six functional variants in a northwestern Indian cohort. Methods: Genetic typing of six MBL2 variants was done by amplification refractory mutation system-polymerase chain reaction. Data were analyzed using suitable statistical tools. Results: Significant difference has been observed in genotypic and allelic distribution between cases and controls for rs11003125. Comparison of allelic distribution for rs1800450 showed significantly high prevalence of A allele in cases than controls. Conclusion: These results indicate that MBL2 variants may act as plausible marker for susceptibility toward RA. Keeping this in view, it is pertinent to screen these variants in other population groups of India.

Acute generalized exanthematous pustulosis: European expert consensus for diagnosis and management.

Acute generalized exanthematous pustulosis (AGEP) is a rare, usually drug-induced, acute pustular rash. Despite the lack of strong data supporting the effectiveness of topical or systemic corticosteroids in this drug reaction, they are widely used. More generally, there is no consensus on the diagnostic modalities and the management of patients with AGEP. We aimed to provide European expert recommendations for the diagnosis and management or patients with AGEP. Members of the ToxiTEN group of the European Reference Network (ERN)-skin, all dermatologists and/or allergologists with expertise in drug reactions, elaborated these recommendations based on their own experience and on a review of the literature. Recommendations were separated into the following categories: professionals involved, assessment of the diagnosis of AGEP, management of the patient and allergological work-up after the acute phase. Consensus was obtained among experts for the list of professionals involved for the diagnosis and management of AGEP, including the minimum diagnostic work-up, the setting of management, the treatments, the modalities and the timing of allergological work-up and follow-up. European experts in drug allergies propose herein consensus on the diagnosis and management of patients with AGEP. A multidisciplinary approach is warranted, including dermatologists, allergologists and pharmacovigilance services.

Nutraceuticals and phytoceuticals in the treatment of schizophrenia: a systematic review and network meta-analysis "Nutra NMA SCZ".

Sub-optimal response in schizophrenia is frequent, warranting augmentation strategies over treatment-as-usual (TAU). We assessed nutraceuticals/phytoceutical augmentation strategies via network meta-analysis. Randomized controlled trials in schizophrenia/schizoaffective disorder were identified via the following databases: PubMed, MEDLINE, EMBASE, Scopus, PsycINFO, CENTRAL, and ClinicalTrials.gov. Change (Standardized Mean Difference = SMD) in total symptomatology and acceptability (Risk Ratio = RR) were co-primary outcomes. Secondary outcomes were positive, negative, cognitive, and depressive symptom changes, general psychopathology, tolerability, and response rates. We conducted subset analyses by disease phase and sensitivity analyses by risk of bias and assessed global/local inconsistency, publication bias, risk of bias, and confidence in the evidence. The systematic review included 49 records documenting 50 studies (n = 2384) documenting 22 interventions. Citicoline (SMD =-1.05,95%CI = -1.85; -0.24), L-lysine (SMD = -1.04,95%CI = -1.84; -0.25), N-acetylcysteine (SMD = -0.87, 95%CI = -1.27; -0.47) and sarcosine (SMD = -0.5,95%CI = -0.87-0.13) outperformed placebo for total symptomatology. High heterogeneity (tau2 = 0.10, I2 = 55.9%) and global inconsistency (Q = 40.79, df = 18, p = 0.002) emerged without publication bias (Egger's test, p = 0.42). Sarcosine improved negative symptoms (SMD = -0.65, 95%CI = -1.10; -0.19). N-acetylcysteine improved negative symptoms (SMD = -0.90, 95%CI = -1.42; -0.39)/general psychopathology (SMD = -0.76, 95%CI = -1.39; -0.13). No compound improved total symptomatology within acute phase studies (k = 7, n = 422). Sarcosine (SMD = -1.26,95%CI = -1.91; -0.60), citicoline (SMD = -1.05,95%CI = -1.65;-0.44), and N-acetylcysteine (SMD = -0.55,95%CI = -0.92,-0.19) outperformed placebo augmentation in clinically stable participants. Sensitivity analyses removing high-risk-of-bias studies confirmed overall findings in all phases and clinically stable samples. In contrast, the acute phase analysis restricted to low risk-of-bias studies showed a superior effect vs. placebo for N-acetylcysteine (SMD = -1.10, 95%CI = -1.75,-0.45), L-lysine (SMD = -1.05,95%CI = -1.55, -0.19), omega-3 fatty acids (SMD = -0.83,95%CI = -1.31, -0.34) and withania somnifera (SMD = -0.71,95%CI = -1.21,-0.22). Citicoline (SMD = -1.05,95%CI = -1.86,-0.23), L-lysine (SMD = -1.04,95%CI = -1.84,-0.24), N-acetylcysteine (SMD = -0.89,95%CI = -1.35,-0.43) and sarcosine (SMD = -0.61,95%CI = -1.02,-0.21) outperformed placebo augmentation of TAU ("any phase"). Drop-out due to any cause or adverse events did not differ between nutraceutical/phytoceutical vs. placebo+TAU. Sarcosine, citicoline, and N-acetylcysteine are promising augmentation interventions in stable patients with schizophrenia, yet the quality of evidence is low to very low. Further high-quality trials in acute phases/specific outcomes/difficult-to-treat schizophrenia are warranted.

Frequency of Leptospira in the Blood of Patients with Fever of Unknown Origin in Sinaloa, Mexico.

Background: Leptospira is a genus of bacteria that causes the zoonotic disease known as leptospirosis, which mainly affects countries with tropical and subtropical climates. Its prevalence may be underestimated because the initial stage of the infection is characterized by presenting a febrile condition that is easily confused with other diseases, such as dengue. This work reports the frequency of leptospirosis in the blood of patients with febrile symptoms of unknown origin. Materials and Methods: A total of 218 peripheral blood samples were analyzed from volunteer participants from Culiacan Sinaloa in June 2019, one half corresponded to patients with undiagnosed febrile symptoms and the other half to asymptomatic volunteers. Data collected included the age and sex of the participants. Leptospira was detected by qPCR using a fragment of the lipL32 gene from the bacteria's genome as a target. Fisher's exact test was used as a statistical method to estimate the relationship between the infection and the data collected. Results: The study group comprised 134 female and 84 male patients ranging from ages 1 to 92 years, averaging 41 years. In this study, Leptospira infection was identified in the blood of 22/218 participating volunteers (10.09%), of which 20/109 (18.34%) presented febrile symptoms, whereas 2/109 (1.83%) were asymptomatic. The most affected participants were women with ages between 27 and 59 years. However, the analysis of the relationship between infection and the variables studied did not show statistical significance. Conclusions: Leptospirosis was detected in blood samples from patients with undiagnosed febrile illness and asymptomatic symptoms in Sinaloa. The lipL32 gene is useful as a target in identifying Leptospira in human blood in the acute phase of the disease.

Using the ClinFIT COVID-19 Instrument to Assess the Functional Impairments Specific to Post-COVID-19 Patients in Romania

Introduction: The COVID-19 pandemic has led to approximately 3.5 million cases in Romania, causing systemic inflammation and over 200 symptoms affecting various body systems. This complexity has challenged rehabilitation systems, necessitating personalized plans tailored to each patient’s illness stage and impairment level. The ISPRM-developed ClinFIT COVID-19 instrument, aligned with the ICF categories, assists in assessing patients during acute, post-acute, and long-term phases. Objective: This study aimed to evaluate and assess functional impairments in post-COVID-19 patients in Romania, with a secondary goal of generating rehabilitation directions. Methods: Data were collected from patients at two Bucharest medical centers, including those with persistent symptoms post-acute phase. Participants were assessed using the adapted ClinFIT COVID-19 instrument, and descriptive statistics were applied. Conclusions: Findings revealed diverse functional impairments in physical, psychological, and social domains among post-COVID-19 patients, with severe impairments more common in those with long-term COVID-19. Complete impairment in complex movement and paid work was noted, affecting one-third of salaried employees and forcing some to retire. In the acute phase, the most frequent functional impairments were sleep, attention, pain sensation, and exercise tolerance functions. In contrast, the most severely affected functions were exercise tolerance and mobility joint functions. Age did not positively correlate with any of the analyzed functions. In the post-acute phase, sleep, energy, and drive functions remained the most frequently affected functions, while the most severely affected was, by far, the moving around function. In the post-acute period, respiratory and respiratory muscle functions strongly correlated with all tasks related to physical activity. In the long COVID-19 phase, remunerative employment was the most severely affected function, while attention functions remained the most frequently affected, similar to the acute phase. The ClinFIT COVID-19 instrument effectively captured these impairments, underscoring the need for comprehensive rehabilitation strategies.

The Injury Progression in Acute Blast-Induced Mild Traumatic Brain Injury in Rats Reflected by Diffusion Tensor Imaging and Immunohistochemical Examination.

Diffusion tensor imaging (DTI) has emerged as a promising neuroimaging tool for detecting blast-induced mild traumatic brain injury (bmTBI). However, lack of refined acute-phase monitoring and reliable imaging biomarkers hindered its clinical application in early diagnosis of bmTBI, leading to potential long-term disability of patients. In this study, we used DTI in a rat model of bmTBI generated by exposing to single lateral blast waves (151.16 and 349.75 kPa, lasting 47.48 ms) released in a confined bioshock tube, to investigate whole-brain DTI changes at 1, 3, and 7 days after injury. Combined assessment of immunohistochemical analysis, transmission electron microscopy, and behavioral readouts allowed for linking DTI changes to synchronous cellular damages and identifying stable imaging biomarkers. The corpus callosum (CC) and brainstem were identified as predominantly affected regions, in which reduced fractional anisotropy (FA) was detected as early as the first day after injury, with a maximum decline occurring at 3 days post-injury before returning to near normal levels by 7 days. Axial diffusivity (AD) values within the CC and brainstem also significantly reduced at 3 days post-injury. In contrast, the radial diffusivity (RD) in the CC showed acute elevation, peaking at 3 days after injury before normalizing by the 7-day time point. Damages to nerve fibers, including demyelination and axonal degeneration, progressed in lines with changes in DTI parameters, supporting a real-time macroscopic reflection of microscopic neuronal fiber injury by DTI. The most sensitive biomarker was identified as a decrease in FA, AD, and an increase in RD within the CC on the third day after injury, supporting the diagnostic utility of DTI in cases of bmTBI in the acute phase.

The Demography of Crisis‐Driven Outflows from Venezuela

AbstractThe Venezuelan exodus represents the largest known displacement of people in recent Latin American history. The regional crisis caused by this mass Venezuelan migration drove the development of multiple interagency initiatives (such as the R4V platform) as well as academic attempts to keep track of outflow intensity. However, little is known about the age and gender composition of the emigrants since most existing literature to date has focused primarily on total volume and country‐specific shares of migration outflows. This study examines the demographics of recent outflows from Venezuela, the chronology of associated changes, and the demographic implications for those remaining in the country. Official counts of Venezuelan‐born populations compiled in seven main destinations are used to estimate annual outflows by age and gender from 2011 to 2021. Changes in the demographic composition of emigration are traced using parameters of the Rogers–Castro model, specifically the children‐to‐labor force dominance, and by decomposing the age contributions to the annual gross migraproduction rate. In the early phase of the crisis (2014–2017), emigration flows had high child dependency ratios. As the crisis entered its most acute phase (peaking in 2019), the mean age of migrants increased. Outward migration has resulted in the current Venezuelan population having 20 percent fewer women of reproductive age and 17.8 percent fewer individuals of working age. Consequently, the share of the population aged 60 or older has increased.

Long-term sequelae after viral meningitis and meningoencephalitis are frequent, even in mildly affected patients, a prospective observational study

IntroductionAn increasing number of studies demonstrate that viral meningitis and meningoencephalitis, even those with a mild course of meningitis, can result in residual sequelae.MethodsWe aimed to investigate the long-term outcome in both viral meningitis and meningoencephalitis/encephalitis patients and impact of long-term sequelae on patients’ social and professional daily lives in a prospective observational study with a follow-up period of 20 months.ResultsA total of 50 patients (12% encephalitis, 58% meningoencephalitis and 30% meningitis) and 21 control persons participated in the study. The most common cause was the tick-borne encephalitis (TBE) virus. The most important persistent signs and symptoms after 2 years were subjective cognitive impairment (36%), fatigue and/or excessive daytime sleepiness (31%), disturbed nighttime sleep (31%) and headaches (13%), as well as feeling more rapidly exhausted after cognitive effort (53%). Independent of disease severity in the acute phase, almost one third of patients still reported mildly impaired social and/or professional life due to the long-term sequelae, with scores in the health status assessment still significantly lower compared to healthy controls.DiscussionRegardless of the severity of the acute illness and despite constant improvement within 2 years, 67% of patients still had persistent signs and symptoms, but these were only relevant to everyday social or professional life in about 30% of these patients.