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Background Monoclonal antibodies (mAbs) effectively treat and prevent various diseases, but their clinical application is hindered by issues related to the route of administration and pharmacokinetics (PK). Intravenous (IV) administration is cumbersome, while subcutaneous (SC) administration is hampered by lower bioavailability and potential for immunogenicity. This study evaluated the efficacy of liposomal formulations in enhancing the subcutaneous (SC) delivery and PK of broadly neutralizing antibodies (bNAbs) directed against HIV., Methods: mAbs were encapsulated in liposomes with and without PEGylation. The liposomes were characterized for particle size, polydispersity index, zeta potential, and release. Thereafter, mice were injected with free mAbs or liposome-encapsulated mAbs, and PK was evaluated., Results: Liposomes exhibited sizes of 85-92 nm with negative surface charges. Encapsulation efficiencies were 61 % for PEGylated and 58 % for non-PEGylated liposomes. Stability testing over 16 weeks revealed that formulations remained stable at 4 °C but showed leakage at 37 C. Cytotoxicity assays confirmed that the liposomal formulations did not affect cell viability or induce apoptosis in HMEC-1 cells. In vivo, PK studies in humanized FcRn mice indicated that the PEGylated formulations generally had higher half-life, Cmax, AUC, and MRT, and lower CL values compared to their non-PEGylated formulations of the same injection type. Both liposomal formulations showed improvements in bioavailability and extended half-life compared to free mAbs administered via SC and IV routes. Compared to the gold standard of IV free mAb injection, SC injection of antibodies encapsulated in PEGylated liposome had up to 80 % higher bioavailability and 45 % extension of half-life. Compared to the SC free mAb injection, the differences were even more pronounced, with liposomal SC injection having up to 113 % higher bioavailability and 81 % extension of half-life., Conclusion: Overall, liposomal encapsulation effectively protected SC injected mAbs from degradation, facilitated sustained release, and improved PK profiles, suggesting a promising strategy for enhancing the therapeutic potential of mAbs in conditions that need repeated injections. Future work should further optimize liposomal formulations to increase loading capacity, stability, and release kinetics., Statement of Significance: This study addresses a challenge in the administration of monoclonal antibodies (mAbs). Intravenous administration requires additional resources, including nursing staff, making it time-consuming and costly. Although subcutaneous (SC) administration offers a less expensive and more patient-friendly option, it suffers from lower bioavailability and potentially shorter half-life. In this study, we encapsulated mAbs in liposomal formulations specifically designed to enhance their pharmacokinetics by promoting efficient lymphatic transport. Compared with both SC and even IV administration of free antibodies, liposomal formulations of mAbs remarkably improve bioavailability and extend the half-life. This innovative approach combines the comfort of SC administration with enhanced pharmacokinetics, addressing the limitations of current SC delivery methods. Liposomal formulations have the ability to greatly improve SC mAb administration by reducing the amount of antibody needed to be administered, reducing the frequency of injections, and potentially protecting against immunogenicity., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Inc.)

Objective: To compare the demographics, clinical characteristics, and in-hospital mortality rates between community-acquired bacterial meningitis cases and postoperative bacterial meningitis., Study Design: Analytical study. Place and Duration of the Study: Department of Infectious Diseases and Clinical Microbiology, Diskapi Yildirim Beyazit Training and Research Hospital, Ankara, Turkiye, from 2016 to 2022., Methodology: A total of 153 patients diagnosed with bacterial meningitis were included and categorised into two groups: 95 (62.1%) with community-acquired bacterial meningitis (CABM) and 58 (37.9%) with postoperative bacterial meningitis (POBM). Demographics, clinical features, laboratory, paraclinical findings, treatments, and outcomes of the cases were compared. Data were retrieved using a standard data collection form from the electronic medical records., Results: A substantial portion (58.8%) of all patients had comorbidities. Fever was the common symptom in all groups. Headache, neck stiffness, nausea, and vomiting were more often observed in the CABM group (p <0.001). Upon admission, the CABM exhibited higher levels of white blood cell count, C-reactive protein, and procalcitonin (p = 0.017, p = 0.004, p = 0.007, respectively). Overall 33.1% had positive cerebrospinal fluid cultures. The overall mortality rate was 26.8%. POBM was associated with longer hospital and intensive care unit (ICU) stays (p <0.001). Shorter treatment durations, lower Glasgow coma scale scores (GCS), higher Charlson Comorbidity Index values, and elevated markers of inflammation were related to mortality., Conclusion: This study illuminates the differences in clinical presentations and outcomes between community-acquired and postoperative bacterial meningitis. It also suggests that factors such as lower GCS scores, comorbidities, and elevated inflammation markers at the last follow-up may be associated with unfavourable clinical outcomes in bacterial meningitis., Key Words: Postoperative meningitis, Central nervous system infection, Cerebrospinal fluid, Antibiotics.

Anti-HIV envelope broadly neutralizing antibodies (bnAbs) are alternatives to conventional antiretrovirals with the potential to prevent and treat infection, reduce latent reservoirs, and/or mediate a functional cure. Clinical trials with "first generation" bnAbs used alone or in combination show promising antiviral effects but also highlight that additional engineering of "enhanced" antibodies will be required for optimal clinical utility, while preserving or enhancing cGMP manufacturing capability. Here we report the engineering of an anti-CD4 binding-site (CD4bs) bnAb, N49P9.3, purified from the plasma of an HIV elite-neutralizer. Through a series of rational modifications we produced a variant that demonstrates: enhanced potency; superior antiviral activity in combination with other bnAbs; low polyreactivity; and longer circulating half-life. Additional engineering for manufacturing produced a final variant, eN49P9, with properties conducive to cGMP production. Overall, these efforts demonstrate the feasibility of developing enhanced anti-CD4bs bnAbs with greatly improved antiviral properties as well as potential translational value.

This study aimed to assess the severity and outcomes of COVID-19 in pregnant women, focusing on laboratory and radiological discrepancies between pregnant women and matched nonpregnant women. In this retrospective cross-sectional analysis, we matched 107 nonpregnant women with 66 pregnant women in terms of age, comorbidities, and the interval between symptom onset and hospital admission. Demographic, clinical, laboratory, and radiological data were collected, and chest CT scans were evaluated using a severity scale ranging from 0 to 5. Logistic regression and adjusted Cox regression models were used to assess the impact of various factors on pregnancy status and mortality rates. Differences in several laboratory parameters, including the neutrophil-to-lymphocyte ratio, liver aminotransferases, alkaline phosphatase, urea, triglycerides, cholesterol, HbA1c, ferritin, coagulation profiles, and blood gases, were detected. Radiologic exams revealed that nonpregnant women had sharper opacities, whereas pregnant women presented with hazy opacities and signs of crypt-organizing pneumonia. A notable difference was also observed in the pulmonary artery diameter. The mortality rate among pregnant women was 4.62%, which was comparable to the 5.61% reported in nonpregnant patients. Compared with nonpregnant patients, pregnancy did not significantly affect the severity or mortality of COVID-19. Our study revealed discernible differences in specific laboratory and imaging markers between pregnant and nonpregnant COVID-19 patients., (© 2024. The Author(s).)

As the only reliable treatment option for end-stage liver diseases, conventional liver transplantation confronts major supply limitations. Accordingly, the decellularization of discarded livers to produce bioscaffolds that support recellularization with progenitor/stem cells has emerged as a promising translational medicine approach. The success of this approach will substantially be determined by the extent of extracellular matrix (ECM) preservation during the decellularization process. Here, we assumed that the matrix metalloproteinase (MMP) inhibition could reduce the ECM damage during the whole liver decellularization of an animal model using a perfusion-based system. We demonstrated that the application of doxycycline as an MMP inhibitor led to significantly higher preservation of collagen, glycosaminoglycans, and hepatic growth factor (HGF) contents, as well as mechanical and structural features, including tensile strength, fiber integrity, and porosity. Notably, produced bioscaffolds were biocompatible and efficiently supported cell viability and proliferation in vitro. We also indicated that produced bioscaffolds efficiently supported HepG2 cell function upon seeding onto liver ECM discs using albumin and urea assay. Additionally, MMP inhibitor pretreated decellularized livers were more durable in contact with collagenase digestion compared to control bioscaffolds in vitro. Using zymography, we confirmed the underlying mechanism that results in these promising effects is through the inhibition of MMP2 and MMP9. Overall, we demonstrated a novel method based on MMP inhibition to ameliorate the ECM structure and composition preservation during liver decellularization as a critical step in fabricating transplantable bioengineered livers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Primary deficiency of coenzyme Q 10 deficiency-4 (CoQ 10 D4) is a heterogeneous disorder affecting different age groups. The main clinical manifestation consists of cerebellar ataxia, exercise intolerance, and dystonia., Case Report: We provide a case of adolescence-onset ataxia, head tremor, and proximal muscle weakness accompanied by psychiatric features and abnormal serum urea (49.4 mg/dL), lactate (7.5 mmol/L), and CoQ10 level (0.4 µg/mL). Brain-MRI demonstrated cerebellar atrophy, thinning of the corpus callosum, and loss of white matter. Whole exome sequencing showed a homozygous missense mutation (c.911C>T; p.A304V) in CoQ8A gene which is a rare mutation and responsible variant of CoQ 10 D4. After supplementary treatment with CoQ 10 50 mg/twice a day for 2 months the clinical symptoms improved., Conclusion: These observations highlight the significance of the early diagnosis of potentially treatable CoQ8A mutation as well as patient education and follow-up. Our findings widen the spectrum of CoQ8A phenotypic features so that clinicians be familiar with the disease not only in severe childhood-onset ataxia but also in adolescence with accompanying psychiatric problems., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Researchers have examined different bio-inspired materials in tissue engineering and regenerative medicine to fabricate scaffolds to address tendon regeneration requirements. We developed fibers based on alginate (Alg) and hydroxyethyl cellulose (HEC) by wet-spinning technique to mimic the fibrous sheath of ECM. Various proportions (25:75, 50:50, 75:25) of 1 % Alg and 4 % HEC were blended to this aim. Two steps of crosslinking with different concentrations of CaCl 2 (2.5 and 5 %) and glutaraldehyde (2.5 %) were used to improve physical and mechanical properties. The fibers were characterized by FTIR, SEM, swelling, degradation, and tensile tests. The in vitro proliferation, viability, and migration of tenocytes on the fibers were also evaluated. Moreover, the biocompatibility of implanted fibers was investigated in an animal model. The results showed ionic and covalent molecular interactions between the components. In addition, by properly maintaining surface morphology, fiber alignment, and swelling, lower concentrations of HEC in the blending provided good degradability and mechanical features. The mechanical strength of fibers was in the range of collagenous fibers. Increasing the crosslinking led to significantly different mechanical behaviors in terms of tensile strength and elongation at break. Because of good in vitro and in vivo biocompatibility, tenocyte proliferation, and migration, the biological macromolecular fibers could serve as desirable tendon substitutes. This study provides more practical insight into tendon tissue engineering in translational medicine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Jagunal homolog 1 (JAGN1) has been recognized as an essential protein in neutrophil function. The mutated JAGN1 is responsible for immunodeficiency related to innate and humoral defense mechanisms. This deficiency impairs neutrophil development and function, leading to recurrent infections and facial dysmorphism as phenotypic consequences of severe congenital neutropenia (SCN). We report two siblings having the reported JAGN1 mutation with different clinical manifestations. Recurrent abscess formation unresponsive to antibiotic therapy, a history of delayed umbilical separation, frequent bacterial or fungal infection, dysmorphic face, failure to thrive, and other coexisting organ abnormalities should prompt physicians to syndromic immunodeficiencies involving neutrophils. Genetic investigations to elucidate the responsible mutation is critical as clinical management varies. Once the diagnosis is confirmed, a multi-disciplinary team should perform further workups to investigate other coexisting malformations and neurodevelopmental evaluation., (© 2023. The Author(s).)

A grid-connected photovoltaic (PV) system operates under fluctuated weather condition has been modeled and characterized based on specific test bed. A mathematical model of a small-scale PV system has been developed mainly for residential usage, and the potential results have been simulated. The proposed PV model based on three PV parameters, which are the photocurrent, IL, the reverse diode saturation current, Io, the ideality factor of diode, n. Accuracy of the proposed model and its parameters evaluated based on different benchmarks. The results showed that the proposed model fitting the experimental results with high accuracy compare to the other models, as well as the I-V characteristic curve. The results of this study can be considered valuable in terms of the installation of a grid-connected PV system in fluctuated climatic conditions.

Results and complications in 100 patients treated over a 3-year period with the laparoscopic approach for clinically diagnosed acute appendicitis are evaluated. They are compared with results and complications in 100 patients with the same diagnosis who had been treated with the open technique performed by the same surgeon during the same 3 years. The results suggest that laparoscopy provides excellent exposure of the appendix regardless of its position. In the absence of pathology of the appendix, laparoscopy allows for a thorough examination of the entire abdomen and pelvis and good exposure and definitive treatment of most surgical conditions encountered. In the event of appendicitis, regardless of its severity, laparoscopic appendectomy results in less postoperative pain, shorter hospital stays, faster return to normal activities, fewer postoperative complications, and superior cosmetic results. Our experience suggests that the laparoscopic approach is the best approach to diagnosis and treatment of the conditions encountered in patients with suspected appendicitis.