High Morbidity Research Articles

A longitudinal study of the blood and urine metabolome of Vipera berus envenomated dogs

Envenomation of dogs by the common European adder (Vipera berus) is associated with high morbidity. The cytotoxic venom of Vipera berus contains enzymes with the potential to cause acute kidney injury, among other insults, however robust biomarkers for such effects are lacking. A prospective observational follow-up study of naturally envenomated dogs and controls was conducted to fill knowledge gaps regarding canine Vipera berus envenomation, attempt to identify novel biomarkers of envenomation and related kidney injury, and elucidate potential long-term effects. Blood and urine samples were analyzed with a global metabolomics approach using liquid chromatography-mass spectrometry, uncovering numerous features significantly different between cases and controls. After data processing and feature annotation, eight features in blood and 24 features in urine were investigated in order to elucidate their biological relevance. Several of these are associated with AKI, while some may also originate from disturbed fatty acid β-oxidation and soft tissue damage. A metabolite found in both blood and a venom reference sample may represent identification of a venom component in case dogs. Our findings suggest that envenomated dogs treated according to current best practice are unlikely to suffer permanent injury.

Ginsenoside Rh2 Reduced Neurogenesis Dysfunction to Alleviate Depression-like Behaviour in CSDS-induced Mice

Background: Depression is a mental health disorder with high morbidity and disability rates that has harmful effects on public health worldwide. Despite many hypotheses about its mechanism have been put forward, its deeper mechanism is still unclear. Nowadays, there are many antidepressants developed by pharmaceutical companies, such as fluoxetine, ketamine, and paroxetine used in clinical practice, but the therapeutic effects are not satisfactory, with serious adverse reactions and drug addiction. Objective: Ginsenoside Rh2 (G-Rh2) is one of the major bioactive ginsenosides extracted from Panax ginseng that has been conducted for the treatment of many inflammatory diseases. However, the possible mechanisms of G-Rh2 involved in these neuroprotective effects on neuroinflammation are currently unclear. Methods: We established a CSDS depression model in normal mice, and then the depressive symptoms of mice were evaluated by a series of behavioral testing. Finally, molecular biology experiments were conducted to demonstrate that G-Rh2 had anti-inflammatory and antidepressant effects. Results: We showed that G-Rh2 (30 mg/kg) significantly relieved depressive behavior in mice via attenuating oxidative stress injury and release of proinflammatory cytokines. Moreover, G-Rh2 reduced impaired neurogenesis in the hippocampus of CSDS-induced mice. Conclusion: We demonstrated the anti-inflammatory and antioxidative effects of G-Rh2 to alleviate depression through improved neurogenesis in depressive mice for the first time. What's more, we aimed to verify the protective effects of G-Rh2 on neuroinflammation and provide novel insights for understanding the roles of G-Rh2 in the treatment of depression

Primary chemoradiation versus neoadjuvant chemotherapy followed by surgery as treatment strategy for locally advanced vulvar carcinoma (VULCANize2)

BackgroundCurrent treatment options for patients with locally advanced vulvar cancer are limited and associated with high morbidity. Therefore, it is important to develop new and safe treatment strategies for this...

Demographic and economic inequality of antenatal care coverage in 4 African countries with a high maternal mortality rate

BackgroundMaternal deaths are concentrated in low and middle-income countries, and Africa accounts for over 50% of the deaths. Women from socioeconomically disadvantaged households have higher morbidity and mortality rates and lower access to maternal health services. Understanding and addressing these inequalities is crucial for achieving the Sustainable Development Goals and improving maternal health outcomes. This study examines the demographic and economic disparities in the utilization of antenatal care (ANC) in four countries with high maternal mortality rates in Africa, namely Nigeria, Chad, Liberia, and Sierra Leone.MethodThe study utilised data from Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS) from Nigeria, Chad, Liberia, and Sierra Leone. The data was obtained from the Health Equity Assessment Toolkit (HEAT) database. The study examined ANC service utilisation inequality in four dimensions such as economic status, education, place of residence, and subnational region across different subgroups by using four summary measures (Difference (D), Absolute Concentration Index (ACI), Population Attributable Risk (PAR), and Population Attributable Factor (PAF)).ResultA varying level of inequality in ANC coverage across multiple survey years was observed in Nigeria, Chad, Liberia, and Sierra Leone. Different regions and countries exhibit varying levels of inequality. Disparities were prominent based on educational attainment and place of residence. Higher level of inequality was generally observed among individuals with higher education and those residing in urban areas. Inequality in ANC coverage was also observed by economic status, subnational region, and other factors in Nigeria, Chad, Liberia, and Sierra Leone. ANC coverage is generally higher among the richest quintile subgroup, indicating inequality. Nigeria and Chad show the highest levels of inequality in ANC coverage across multiple measures. Sierra Leone displays some variation with higher coverage among the poorest quintile subgroup.Conclusion and recommendationInequalities in ANC coverage exist across age groups and survey years in Nigeria, Chad, Liberia, and Sierra Leone. Disparities are prominent based on education, residence, and economic status. Efforts should focus on improving access for vulnerable groups, enhancing education and awareness, strengthening healthcare infrastructure, and addressing economic disparities.

Status of vector protection measures and awareness regarding vector borne diseases in families residing in a Nirmal Gram Puraskar village in India.

Mosquito-borne diseases are increasing problems in various parts of the world, causing high mortality and morbidity for humans. This study was done to assess the vector protection measures taken by rural BPL (below-poverty-line) families, and to assess the awareness about vector-borne diseases along with Total Sanitation Campaign (TSC) in rural BPL families. A cross-sectional study was conducted in rural areas, which won Nirmal Gram Puraskar Award, among 96 BPL families for a period of three months. These families (every 5th) were selected by systematic random sampling until we reached a sample size. Basic sociodemographic details, status of vector protection measures, solid waste management, vector- borne diseases and total sanitation campaign details were collected from the study participants. Pre-tested, semi-structured questionnaire was applied to the head of the families which included sanitation status at home by a house-to-house visit. The data collected was analysed using SPSS version 20. Data was presented as frequency, percentages, mean and SD. Among 96 families (454 adults and children) studied 84 (87.5%) were males and 12 (12.5%) were females. 291 (64.1%) were using one or the other mosquito protection measures, 52 (54.2%) were using bednets and 23 (23.9%) were using coils. 12 families (12.5%) were not using any mosquito protection measures. In our study, 66 (68.8%) families had individual household latrine (IHHL) and 50 (52.1%) had open drainage. Even though 314 participants had an access to individual household latrine, 20 (6.36%) had practice of open-air defecation compared to 127 (90.7%) who practiced open-air defecation without an access to individual household latrine. When asked about the awareness regarding vector-borne diseases, 56 (58.3%) were aware about chikungunya, 47 (48.9%) about dengue, 46 (47.9%) about malaria, 14 (14.6%) and only 5 (5.2%) families were aware about Japanese encephalitis. In this study, 37 (38.5%) were aware about the total sanitation campaign and 40 (41.6%) were aware about government support for sanitation. While there is a general awareness of vector-borne diseases, the implementation of vector protection measures is not uniform across the village. There is a need for targeted interventions to improve the effectiveness of vector protection measures and increase awareness among the community.

Doxycycline inhibits neurotropic enterovirus proliferation in vitro

Human enteroviruses (EVs) represent a global public health concern due to their association with a range of serious pediatric illnesses. Despite the high morbidity and mortality exerted by EVs, no broad-spectrum antivirals are currently available. Herein, we presented evidence that doxycycline can inhibit in vitro replication of various neurotropic EVs, including enterovirus A71 (EV-A71), enterovirus D68 (EV-D68), and coxsackievirus (CV)-A6, in a dose-dependent manner. Further investigations indicated that the drug primarily acted at the post-entry stage of virus infection in vitro, with inhibitory effects reaching up to 89% for EV-A71 when administered two hours post-infection. These findings provide valuable insights for the development of antiviral drugs against EV infections.

Deciphering the Molecular Mechanisms behind Drug Resistance in Ovarian Cancer to Unlock Efficient Treatment Options.

Ovarian cancer is a highly lethal form of gynecological cancer. This disease often goes undetected until advanced stages, resulting in high morbidity and mortality rates. Unfortunately, many patients experience relapse and succumb to the disease due to the emergence of drug resistance that significantly limits the effectiveness of currently available oncological treatments. Here, we discuss the molecular mechanisms responsible for resistance to carboplatin, paclitaxel, polyadenosine diphosphate ribose polymerase inhibitors, and bevacizumab in ovarian cancer. We present a detailed analysis of the most extensively investigated resistance mechanisms, including drug inactivation, drug target alterations, enhanced drug efflux pumps, increased DNA damage repair capacity, and reduced drug absorption/accumulation. The in-depth understanding of the molecular mechanisms associated with drug resistance is crucial to unveil new biomarkers capable of predicting and monitoring the kinetics during disease progression and discovering new therapeutic targets.

The safety of trastuzumab deruxtecan (DS-8201) with a focus on interstitial lung disease and/or pneumonitis: A systematic review and single-arm meta-analysis.

Previous studies involving risk-benefit analysis of trastuzumab deruxtecan (DS-8201) have indicated the benefit of this treatment, although it may increase the risk of interstitial lung disease (ILD) and/or pneumonitis in certain patients. This study aimed to assess the safety of DS-8201. A search was done for relevant articles in four electronic databases: PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov. All reports published up until November 2, 2022, were included, and study types were restricted to clinical trials; the last search was then updated to January 10, 2023. We also assessed the quality of the literature with the Cochrane Handbook for Systematic Reviews of Interventions and the Methodological Index for Non-Randomized Studies tool, and then performed a meta-analysis with R version 4.2.1. A total of 1428 patients reported in 13 articles were included in this study. The analysis revealed that the most common all-grade treatment-emergent adverse events (TEAEs) were nausea and fatigue. The most common TEAE of grade 3 or above (grade ≥3) was neutropenia. The incidences of ILD and/or pneumonitis for all-grade and grade ≥3 TEAEs were 12.5% and 2.2%, respectively. This comprehensive summary of the incidence of TEAEs associated with DS-8201 in clinical trials provides an important guide for clinicians. The most common TEAEs were gastrointestinal reactions and fatigue; meanwhile, the most common grade ≥3 TEAE was hematological toxicity. ILD and/or pneumonitis were specific adverse drug reactions associated with DS-8201, of which physicians should be particularly aware for their higher morbidity and rates of grade ≥3 TEAEs.

Antiviral Activities of Heparan Sulfate Mimetic RAFT Polymers Against Mosquito-borne Viruses.

Mosquito-borne viruses are a major worldwide health problem associated with high morbidity and mortality rates and significant impacts on national healthcare budgets. The development of antiviral drugs for both the treatment and prophylaxis of these diseases is thus of considerable importance. To address the need for therapeutics with antiviral activity, a library of heparan sulfate mimetic polymers was screened against dengue virus (DENV), Yellow fever virus (YFV), Zika virus (ZIKV), and Ross River virus (RRV). The polymers were prepared by RAFT polymerization of various acidic monomers with a target MW of 20 kDa (average Mn ∼ 27 kDa by GPC). Among the polymers, poly(SS), a homopolymer of sodium styrenesulfonate, was identified as a broad spectrum antiviral with activity against all the tested viruses and particularly potent inhibition of YFV (IC50 = 310 pM). Our results further uncovered that poly(SS) exhibited a robust inhibition of ZIKV infection in both mosquito and human cell lines, which points out the potential functions of poly(SS) in preventing mosquito-borne viruses associated diseases by blocking viral transmission in their mosquito vectors and mitigating viral infection in patients.

New Biomarker Candidates of Sepsis: Diagnostic and Prognostic Value of Presepsin, Angiopoietin 1 and 2

Objective: Sepsis is an uncontrolled inflamatory response that occurs in the body towards infection. It’s an important clinical picture that is seen in high morbidity and mortality so early diagnose and treatment areimportant. For that reason, for the septic cases to get early diagnosis and to predict the prognosis, new biomarkers are needed nowadays. Presepsin, angiopoietin 1 and angiopoietin II are biomarkers that are not usedroutinely yet, in our study, according to the new description given in Sepsis 3 meeting, in cases that are diagnosed with sepsis, we aimed at comparing diagnostic and prognostic values of these biomarkers. Methods: In our study, there were two groups. Patient group consisting of 48 cases with 33 men and 15 women and control group consisting of 42 cases with 23 men and 19 women. Control group is selected within patient relatives with similarities of age and sex. Demographic datas, accompanying diseases, APACHE II, SAPS and SOFA scores counted in the first 24 hours, leukocyte count, eritrocyte sedimentation rate, C-reactive protein, procalcitonin value, culture sampling results (blood, urine, sputum, endotracheal aspirate) that are measured in their stays, 7th and 28th day mortality counts after their ICU stays are written down. Presepsin, angiopoietin I and angiopoietin II are detected by sandwich ELISA method. Results: According to demographic features there isn’t any significant statistical difference between the patient group and the control group (p>0.005). In patient group Presepsin, angiopoietin I and angiopoietin II values were statistically high significantly compared to the control group (p<0.001). After the evaluation, serumpresepsin value noticed that has a diagnostic value in the diagnosis of sepsis (EAA: 0.74, 95%GA: 0.64–0.85, p<0.001). The suggested border value for this value is predicted as 0.47, 73%sensitivity and 62% specificity are determined. Serum angiopoietin I value noticed that has a diagnostic value in the diagnosis of sepsis (EAA: 0.80, 95%GA: 0.71–0.89, p<0.001). The suggested border value for this value is predicted as 178.24, 69% sensitivity and 69% specificity are determined. Serum angiopoietin II value noticed that has a diagnostic value in the diagnosis of sepsis (EAA: 0.89, 95% GA: 0.82–0.95, p<0.001). The suggested border value for this value is predicted as 77.56, 84% sensitivity and 83% specificity are determined. Conclusions: In our study, presepsin, angiopoietin I and angiopoietin II values are determined as statistically high according to healthy control group and are found successful with high sensitivity and specificity in diagnosing. Presepsin, angiopoietin I and angiopoietin II values in septic patients are found successful with high sensitivity and specificity at 7th and 28th days mortality prediction.

Oroxin A alleviates early brain injury after subarachnoid hemorrhage by regulating ferroptosis and neuroinflammation

BackgroundSubarachnoid hemorrhage (SAH), a severe subtype of stroke, is characterized by notably high mortality and morbidity, largely due to the lack of effective therapeutic options. Although the neuroprotective potential of PPARg and Nrf2 has been recognized, investigative efforts into oroxin A (OA), remain limited in preclinical studies.MethodsSAH was modeled in vivo through filament perforation in male C57BL/6 mice and in vitro by exposing HT22 cells to hemin to induce neuronal damage. Following the administration of OA, a series of methods were employed to assess neurological behaviors, brain water content, neuronal damage, cell ferroptosis, and the extent of neuroinflammation.ResultsThe findings indicated that OA treatment markedly improved survival rates, enhanced neurological functions, mitigated neuronal death and brain edema, and attenuated the inflammatory response. These effects of OA were linked to the suppression of microglial activation. Moreover, OA administration was found to diminish ferroptosis in neuronal cells, a critical factor in early brain injury (EBI) following SAH. Further mechanistic investigations uncovered that OA facilitated the translocation of nuclear factor erythroid 2-related factor 2 (Nrf-2) from the cytoplasm to the nucleus, thereby activating the Nrf2/GPX4 pathway. Importantly, OA also upregulated the expression of FSP1, suggesting a significant and parallel protective effect against ferroptosis in EBI following SAH in synergy with GPX4.ConclusionIn summary, this research indicated that the PPARg activator OA augmented the neurological results in rodent models and diminished neuronal death. This neuroprotection was achieved primarily by suppressing neuronal ferroptosis. The underlying mechanism was associated with the alleviation of cellular death through the Nrf2/GPX4 and FSP1/CoQ10 pathways.

Risk factors and prognostic significance of early postoperative complications for patients who underwent pneumonectomy for lung cancer

BackgroundAlthough pneumonectomy has relatively high mortality and morbidity rates, it remains valid in the surgical treatment of lung cancer. This study aims to evaluate the prognostic significance of postoperative complications after pneumonectomy and demonstrate the risk factors related to early postoperative complications.MethodsPatients who underwent pneumonectomy for non-small cell lung cancer between January 2008 and May 2021 were included in the study. Factors related to the development of early postoperative complications and overall survival were evaluated by univariate and multivariate analyses.ResultsA total of 136 patients were included in the study. Early postoperative complications were seen in 33 (24.3%) patients and late postoperative complications in 7 (5.1%) patients. The amount of cigarette smoking, and the operation side were the independent variables that affect the development of early postoperative complications. In multivariate analysis, smoking amount and pericardial invasion were associated with the development of postoperative hemorrhage, and advanced age was associated with the development of postoperative pneumonia.ConclusionsEarly postoperative complications have a negative effect on the prognosis after pneumonectomy therefore careful patient selection and preoperative risk assessment are essential to minimize the occurrence of complications and improve patient outcomes.Trial registrationThis observational study was approved by the (Ethical Committee of Dr. Suat Seren Chest Diseases and Chest Surgery Education and Research Center) Institutional Review Board of our center (E-49109414-604.02.02-218625439).

3DFRINet: A Framework for the Detection and Diagnosis of Fracture Related Infection in Low Extremities Based on 18F-FDG PET/CT 3D Images

Fracture related infection (FRI) is one of the most devastating complications after fracture surgery in the lower extremities, which can lead to extremely high morbidity and medical costs. Therefore, early comprehensive evaluation and accurate diagnosis of patients are critical for appropriate treatment, prevention of complications, and good prognosis. 18Fluoro-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is one of the most commonly used medical imaging modalities for diagnosing FRI. With the development of deep learning, more neural networks have been proposed and become powerful computer-aided diagnosis tools in medical imaging. Therefore, a fully automated two-stage framework for FRI detection and diagnosis, 3DFRINet (Three Dimension FRI Network), is proposed for 18F-FDG PET/CT 3D imaging. The first stage can effectively extract and fuse the features of both modalities to accurately locate the lesion by the dual-branch design and attention module. The second stage reduces the dimensionality of the image by using the maximum intensity projection, which retains the effective features while reducing the computational effort and achieving excellent diagnostic performance. The diagnostic performance of lesions reached 91.55% accuracy, 0.9331 AUC, and 0.9250 F1 score. 3DFRINet has an advantage over six nuclear medicine experts in each classification metric. The statistical analysis shows that 3DFRINet is equivalent or superior to the primary nuclear medicine physicians and comparable to the senior nuclear medicine physicians. In conclusion, this study first proposed a method based on 18F-FDG PET/CT three-dimensional imaging for FRI location and diagnosis. This method shows superior lesion detection rate and diagnostic efficiency and therefore has good prospects for clinical application.

COVID-19 Prevention and Mitigation Decision-Making Processes While Navigating Chronic Disease Care: Perspectives of Black Adults with Heart Failure and Diabetes.

Heart failure and diabetes are comorbidities that disproportionately contribute to high morbidity and mortality among Blacks. Further compounding the racial and ethnic disparities in COVID-19 health outcomes, Blacks with cardiometabolic diseases are at high risk of experiencing serious complications or mortality from COVID-19. This study aimed to assess how Blacks with heart failure and diabetes navigated chronic care management during the COVID-19 pandemic. A mixed methods study including in-depth interviews and surveys with adults diagnosed with heart failure and diabetes (n = 17) was conducted in 2021-2022. Verbatim transcripts were analyzed using a thematic analysis approach. Participants reported that while the pandemic initially caused delays in access to health services, shifts to telemedicine allowed for continued care despite preferences for in-person appointments. Various sources of information were used in different ways to make decisions on how to best reduce health risks due to COVID-19, but individuals and institutions affiliated with science and medicine, or who promoted information from these sources, were considered to be the most trusted sources of information among those who relied on outside guidance when making health-related decisions. Individuals' self-awareness of their own high-risk status and perceived control over their exposure levels to the virus informed what COVID-19 prevention and mitigation strategies people used. Information backed by scientific data was an important health communication tool that alongside other factors, such as fear of mortality due to COVID-19, encouraged individuals to get vaccinated and adopt other COVID-19 prevention and mitigation behaviors.

A systematic review and meta-analysis of diagnostic test accuracy of chest ultrasound in diagnosing pediatric pulmonary tuberculosis.

Despite medical advancement, pediatric pulmonary tuberculosis (PTB) still has high morbidity and mortality, due to challenging detection in clinical practice. Ultrasound has been touted as the next best diagnostic tool but currently, this claim is unfounded. Therefore, this study aims to systematically review the diagnostic parameters of chest ultrasound in diagnosing pediatric PTB. The literature search started and ended on December 23, 2023. We searched MEDLINE, Cochrane Library, Pubmed, Science Direct, and Google Scholar. Our research question could be formulated as "In pediatric patients who present with signs and symptoms of PTB such as fever, cough, and poor weight gain, how accurate is chest ultrasound in ruling in and ruling out pediatric PTB when the diagnosis is compared to culture, PCR or CXR?" This systematic review adhered to the PRISMA-DTA guidelines while the meta-analysis was conducted with STATA program using the "midas" and "metandi" commands. There are five studies included with 137 positive PTB children. The combined sensitivity is 84% (95% confidence interval [CI]: 76-89), specificity of 38% (95% CI: 24-54), and summary receiver operating curve yields an area under the curve of 0.83 (95% CI: 0.80-0.86). The I2 value is 24% (95% CI: 0-100) with a p-value of 0.13. The combined negative predictive value is 0.68 (95% CI: 0.58-0.79), and the positive predictive value is 0.57 (95% CI: 0.51-0.63). The positive likelihood ratio is 1 with a 6% increase from the baseline while the negative likelihood ratio is 0.43 with a 12% decrease from the baseline. Chest ultrasound is sensitive but currently could neither exclude nor confirm pediatric PTB.

Prediction of hospital-acquired influenza using machine learning algorithms: a comparative study

BackgroundHospital-acquired influenza (HAI) is under-recognized despite its high morbidity and poor health outcomes. The early detection of HAI is crucial for curbing its transmission in hospital settings.AimThis study aimed to investigate factors related to HAI, develop predictive models, and subsequently compare them to identify the best performing machine learning algorithm for predicting the occurrence of HAI.MethodsThis retrospective observational study was conducted in 2022 and included 111 HAI and 73,748 non-HAI patients from the 2011–2012 and 2019–2020 influenza seasons. General characteristics, comorbidities, vital signs, laboratory and chest X-ray results, and room information within the electronic medical record were analysed. Logistic Regression (LR), Random Forest (RF), Extreme Gradient Boosting (XGB), and Artificial Neural Network (ANN) techniques were used to construct the predictive models. Employing randomized allocation, 80% of the dataset constituted the training set, and the remaining 20% comprised the test set. The performance of the developed models was assessed using metrics such as the area under the receiver operating characteristic curve (AUC), the count of false negatives (FN), and the determination of feature importance.ResultsPatients with HAI demonstrated notable differences in general characteristics, comorbidities, vital signs, laboratory findings, chest X-ray result, and room status compared to non-HAI patients. Among the developed models, the RF model demonstrated the best performance taking into account both the AUC (83.3%) and the occurrence of FN (four). The most influential factors for prediction were staying in double rooms, followed by vital signs and laboratory results.ConclusionThis study revealed the characteristics of patients with HAI and emphasized the role of ventilation in reducing influenza incidence. These findings can aid hospitals in devising infection prevention strategies, and the application of machine learning-based predictive models especially RF can enable early intervention to mitigate the spread of influenza in healthcare settings.

Recent advances on anti-HIV chimeric antigen receptor-T-cell treatment to provide sustained HIV remission.

Successful sustained remission of HIV infection has been achieved after CCR5Δ32/Δ32 allogeneic hematopoietic stem cell transplantation for treatment of leukemia in a small cohort of people living with HIV (PLWH). This breakthrough demonstrated that the goal of curing HIV was achievable. However, the high morbidity and mortality associated with bone marrow transplantation limits the routine application of this approach and provides a strong rationale for pursuing alternative strategies for sustained long-term antiretroviral therapy (ART)-free HIV remission. Notably, long-term immune-mediated control of HIV replication observed in elite controllers and posttreatment controllers suggests that potent HIV-specific immune responses could provide sustained ART-free remission in PLWH. The capacity of chimeric antigen receptor (CAR)-T cells engineered to target malignant cells to induce remission and cure in cancer patients made this an attractive approach to provide PLWH with a potent HIV-specific immune response. Here, we review the recent advances in the design and application of anti-HIV CAR-T-cell therapy to provide a functional HIV cure. HIV reservoirs are established days after infection and persist through clonal expansion of infected cells. The continuous interaction between latently infected cells and the immune system shapes the landscape of HIV latency and likely contributes to ART-free viral control in elite controllers. CAR-T cells can exhibit superior antiviral activity as compared with native HIV-specific T cells, particularly because they can be engineered to have multiple HIV specificities, resistance to HIV infection, dual costimulatory signaling, immune checkpoint inhibitors, stem cell derivation, CMV TCR coexpression, and tissue homing ligands. These modifications can significantly improve the capacities of anti-HIV CAR-T cells to prevent viral escape, resist HIV infection, and enhance cytotoxicity, persistence, and tissue penetration. Collectively, these novel modifications of anti-HIV CAR-T cell design have increased their capacity to control HIV infection. Anti-HIV CAR-T cells can be engineered to provide potent and sustained in-vitro and in-vivo antiviral function. The combination of anti-HIV CAR-T cells with other immunotherapeutics may contribute to long-term HIV remission in PLWH.

Highly Pathogenic Avian Influenza (HPAI) H5 Clade 2.3.4.4b Virus Infection in Birds and Mammals.

Avian influenza viruses (AIVs) are highly contagious respiratory viruses of birds, leading to significant morbidity and mortality globally and causing substantial economic losses to the poultry industry and agriculture. Since their first isolation in 2013-2014, the Asian-origin H5 highly pathogenic avian influenza viruses (HPAI) of clade 2.3.4.4b have undergone unprecedented evolution and reassortment of internal gene segments. In just a few years, it supplanted other AIV clades, and now it is widespread in the wild migratory waterfowl, spreading to Asia, Europe, Africa, and the Americas. Wild waterfowl, the natural reservoir of LPAIVs and generally more resistant to the disease, also manifested high morbidity and mortality with HPAIV clade 2.3.4.4b. This clade also caused overt clinical signs and mass mortality in a variety of avian and mammalian species never reported before, such as raptors, seabirds, sealions, foxes, and others. Most notably, the recent outbreaks in dairy cattle were associated with the emergence of a few critical mutations related to mammalian adaptation, raising concerns about the possibility of jumping species and acquisition of sustained human-to-human transmission. The main clinical signs and anatomopathological findings associated with clade 2.3.4.4b virus infection in birds and non-human mammals are hereby summarized.

Children with Hirschsprung's disease have high morbidity in the first 5 years of life.

Hirschsprung's disease is a rare congenital anomaly of the colon with absence of the ganglionic nerve cells. The treatment of the anomaly is surgical. This population-based data-linkage cohort study was part of the EUROlinkCAT project and investigated mortality and morbidity for the first 5 years of life for European children diagnosed with Hirschsprung's disease. Nine population-based registries in five countries from the European surveillance of congenital anomalies network (EUROCAT) participated. Data on children born 1995-2014 and diagnosed with Hirschsprung's disease were linked to hospital databases. All analyses were adjusted for region and length of follow-up, which differed by registry. The study included 680 children with Hirschsprung's disease. One-year survival was 97.7% (95% CI: 96.4-98.7). Overall, 85% (82-87) had a code for a specified intestinal surgery within the first year increasing to 92% (90-94) before age 5 years. The median age at the first intestinal surgery up to 5 years was 28 days (11-46) and the median number of intestinal surgical procedures was 3.5 (3.1-3.9). Thirty days mortality after neonatal surgery (within 28 days after birth) was 0.9% (0.2-2.5) for children with a code for intestinal surgery within the first 28 days after birth and there were no deaths for children with a code for stoma surgery in the neonatal period. Children with Hirschsprung's disease have a high morbidity in the first 5 years of life requiring more surgical procedures in addition to the initial surgery. Mortality after neonatal surgery is low.

Current State and Future Perspective of Diabetic Wound Healing Treatment: Present Evidence from Clinical Trials.

Diabetes is a chronic metabolic condition that is becoming more common and is characterised by sustained hyperglycaemia and long-term health effects. Diabetes-related wounds often heal slowly and are more susceptible to infection because of hyperglycaemia in the wound beds. The diabetic lesion becomes harder to heal after planktonic bacterial cells form biofilms. A potential approach is the creation of hydrogels with many functions. High priority is given to a variety of processes, such as antimicrobial, pro-angiogenesis, and general pro-healing. Diabetes problems include diabetic amputations or chronic wounds (DM). Chronic diabetes wounds that do not heal are often caused by low oxygen levels, increased reactive oxygen species, and impaired vascularization. Several types of hydrogels have been developed to get rid of contamination by pathogens; these hydrogels help to clean up the infection, reduce wound inflammation, and avoid necrosis. This review paper will focus on the most recent improvements and breakthroughs in antibacterial hydrogels for treating chronic wounds in people with diabetes. Prominent and significant side effects of diabetes mellitus include foot ulcers. Antioxidants, along with oxidative stress, are essential to promote the healing of diabetic wounds. Some of the problems that can come from a foot ulcer are neuropathic diabetes, ischemia, infection, inadequate glucose control, poor nutrition, also very high morbidity. Given the worrying rise in diabetes and, by extension, diabetic wounds, future treatments must focus on the rapid healing of diabetic wounds.