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In this randomized trial, HIV-positive adults with tuberculous meningitis were assigned to receive 6 to 8 weeks of dexamethasone or placebo in addition to tuberculosis treatment. No benefit of dexamethasone was observed.

Transdermal delivery provides numerous benefits over conventional routes of administration. However, this strategy is generally limited to a few molecules with specific physicochemical properties (low molecular weight, high potency, and moderate lipophilicity) due to the barrier function of the stratum corneum layer. Researchers have developed several physical enhancement techniques to expand the applications of the transdermal field; among these, microneedle technology has recently emerged as a promising platform to deliver therapeutic agents of any size into and across the skin. Typically, hydrophilic biomolecules cannot penetrate the skin by passive diffusion. Microneedle insertion disrupts skin integrity and compromises its protective function, thus creating pathways (microchannels) for enhanced permeation of macromolecules. Microneedles not only improve stability but also enhance skin delivery of various biomolecules. Academic institutions and industrial companies have invested substantial resources in the development of microneedle systems for biopharmaceutical delivery. This review article summarizes the most recent research to provide a comprehensive discussion about microneedle-mediated delivery of macromolecules, covering various topics from the introduction of the skin, transdermal delivery, microneedles, and biopharmaceuticals (current status, conventional administration, and stability issues), to different microneedle types, clinical trials, safety and acceptability of microneedles, manufacturing and regulatory issues, and the future of microneedle technology.

PurposeThis study investigated in vitro transdermal delivery of methotrexate through dermatomed porcine ear and cadaver human skin treated with poly (D,L-lactide-co-glycolide) acid microneedles or fractional ablative laser.MethodsPLGA microneedles were fabricated and characterized using scanning electron microscopy and mechanical assessment techniques. The integrity of treated skin was evaluated by rheometer, transepidermal water loss, and skin electrical resistance measurements. Successful skin microporation was demonstrated by dye binding, histology, pore uniformity, confocal laser microscopy, and DermaScan studies. In vitro permeation experiment was performed on Franz diffusion cells to determine drug delivery into and across the skin.ResultsBoth physical treatments resulted in a considerable decrease in skin resistance and an increase in transepidermal water loss value. The laser-created microchannels were significantly larger than those formed by microneedles (p < 0.05). An effective force of 41.04 ± 18.33 N was required to achieve 100% penetration efficiency of the microneedles. For both porcine ear and human skin, laser ablation provided a significantly higher methotrexate permeability into the receptor chamber and skin layers compared to microneedle poration and untreated skin (p < 0.05).ConclusionsBoth fractional ablative laser and polymeric microneedles markedly enhanced in vitro transdermal delivery of methotrexate into and across skin.

The coronavirus disease 2019 (COVID-19) pandemic causes fear, as its immediate consequences for the public have produced unprecedented challenges for the education and healthcare systems. We aimed to validate the fear of COVID-19 scale (FCoV-19S) and examine the association of its scores with health literacy and health-related behaviors among medical students. A cross-sectional study was conducted from 7 to 29 April 2020 on 5423 students at eight universities across Vietnam, including five universities in the North, one university in the Center, two universities in the South. An online survey questionnaire was used to collect data on participants’ characteristics, health literacy, fear of COVID-19 using the FCoV-19S, and health-related behaviors. The results showed that seven items of the FCoV-19S strongly loaded on one component, explained 62.15% of the variance, with good item–scale convergent validity and high internal consistency (Cronbach’s alpha = 0.90). Higher health literacy was associated with lower FCoV-19S scores (coefficient, B, −0.06; 95% confidence interval, 95%CI, −0.08, −0.04; p < 0.001). Older age or last academic years, being men, and being able to pay for medication were associated with lower FCoV-19S scores. Students with higher FCoV-19S scores more likely kept smoking (odds ratio, OR, 1.11; 95% CI, 1.08, 1.14; p < 0.001) or drinking alcohol (OR, 1.04; 95% CI, 1.02, 1.06; p < 0.001) at an unchanged or higher level during the pandemic, as compared to students with lower FCoV-19S scores. In conclusion, the FCoV-19S is valid and reliable in screening for fear of COVID-19. Health literacy was found to protect medical students from fear. Smoking and drinking appeared to have a negative impact on fear of COVID-19. Strategic public health approaches are required to reduce fear and promote healthy lifestyles during the pandemic.

In the field of bioinspired soft robotics, to accomplish sophisticated tasks in human fingers, electroactive artificial muscles are under development. However, most existing actuators show a lack of high bending displacement and irregular response characteristics under low input voltages. Here, based on metal free covalent triazine frameworks (CTFs), we report an electro-ionic soft actuator that shows high bending deformation under ultralow input voltages that can be implemented as a soft robotic touch finger on fragile displays. The as-synthesized CTFs, derived from a polymer of intrinsic microporosity (PIM-1), were combined with poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT-PSS) to make a flexible electrode for a high-performance electro-ionic soft actuator. The proposed soft touch finger showed high peak-to-peak displacement of 17.0 mm under ultralow square voltage of ±0.5 V, with 0.1 Hz frequency and 4 times reduced phase delay in harmonic response compared with that of a pure PEDOT-PSS-based actuator. The significant actuation performance is mainly due to the unique physical and chemical configurations of CTFs electrode with highly porous and electrically conjugated networks. On a fragile display, the developed soft robotic touch finger array was successfully used to perform soft touching, similar to that of a real human finger; device was used to accomplish a precise task, playing electronic piano. Actuators often show a lack of high bending displacement with back relaxation and irregular response characteristics under low input voltages. Here, the authors demonstrate a covalent triazine framework-based electroionic soft actuator that shows controllable high bending deformation under low input voltages.

Vaccination represents a critical preventive strategy in the current global healthcare system, serving as an indispensable intervention against diverse pathogenic threats. Although conventional immunization relies predominantly on hypodermic needle-based administration, this method carries substantial limitations, including needle-associated fear, bloodborne pathogen transmission risks, occupational injuries among healthcare workers, waste management issues, and dependence on trained medical personnel. Microneedle technology has emerged as an innovative vaccine delivery system, offering convenient, effective, and minimally invasive administration. These microscale needle devices facilitate targeted antigen delivery to epidermal and dermal tissues, where abundant populations of antigen-presenting cells, specifically Langerhans and dermal dendritic cells, provide robust immunological responses. Multiple research groups have extensively investigated microneedle-based vaccination strategies. This transdermal delivery technique offers several advantages, notably circumventing cold-chain requirements and enabling self-administration. Numerous preclinical investigations and clinical trials have demonstrated the safety profile, immunogenicity, and patient acceptance of microneedle-mediated vaccine delivery across diverse immunization applications. This comprehensive review examines the fundamental aspects of microneedle-based immunization, including vaccination principles, transcutaneous immunization strategies, and microneedle-based transdermal delivery—including classifications, advantages, and barriers. Furthermore, this review addresses critical technical considerations, such as treatment efficacy, application methodologies, wear duration, dimensional optimization, manufacturing processes, regulatory frameworks, and sustainability considerations, followed by an analysis of the future perspective of this technology.

Silver nanoparticles have attracted great interests widely in medicine due to its great characteristics of antibacterial activity. In this research, the antibacterial activity and biocompatibility of a topical gel synthesized from polyvinyl alcohol, chitosan, and silver nanoparticles were studied. Hydrogels with different concentrations of silver nanoparticles (15 ppm, 30 ppm, and 60 ppm) were evaluated to compare their antibacterial activity, nanoparticles’ sizes, and in vivo behaviors. The resulted silver nanoparticles in the hydrogel were characterized by TEM showing the nanoparticles’ sizes less than 22 nm. The in vitro results prove that the antibacterial effects of all of the samples are satisfied. However, the in vivo results demonstrate the significant difference among different hydrogels in wound healing, where hydrogel with 30 ppm shows the best healing rate.

Bone cement is used as a mortar for securing bone implants, as bone void fillers or as spacers in orthopaedic surgery. Antibiotic-loaded bone cements (ALBCs) have been used to prevent and treat prosthetic joint infections by providing a high antibiotic concentration around the implanted prosthesis. High antibiotic concentrations are, on the other hand, often associated with tissue toxicity. Controlling antibiotic release from ALBCS is key to achieving effective infection control and promoting prosthesis integration with the surrounding bone tissue. However, current ALBCs still need significant improvement in regulating antibiotic release. In this review, we first provide a brief introduction to prosthetic joint infections, and the background concepts of therapeutic efficacy and toxicity in antibiotics. We then review the current state of ALBCs and their release characteristics before focusing on the research and development in controlling the antibiotic release and osteo-conductivity/inductivity. We then conclude by a discussion on the need for better in vitro experiment designs such that the release results can be extrapolated to predict better the local antibiotic concentrations in vivo.

We report a case of IgG4-related dacryoadenitis and sialadenitis (Mikulicz’s disease) with acquired hemophilia A (AHA) in a pediatric patient. An 11-year-old female presented with intermittent swelling of the bilateral upper eyelids and neck areas. Clinical examination revealed bilateral swollen upper eyelids with palpable mass lesions in the lacrimal fossa. The submandibular and sublingual glands were enlarged, tender, and movable. Neck ultrasound showed bilateral gland enlargement with irregular hypoechoic parenchyma. Maxillofacial magnetic resonance imaging (MRI) revealed bilateral lacrimal glands enlargement, homogeneous enlarged bilateral submandibular and parotid glands, measuring 4.7 × 3.9 cm. Laboratory investigation showed increased activated partial prothromboplastin time (80.9 s), markedly decreased FVIII activity (0.6%), a high titer of FVIII inhibitor (480 Bethesda units/mL), and a remarkable increase in serum IgG4 level (1005.68 mg/dL). A left submandibular gland biopsy revealed marked lympho-plasmacytic infiltration with scattered eosinophils. Immunohistochemical staining for IgG4 showed numerous IgG4-positive plasma cells (>100 per high-power field), with a ratio of IgG4-positive to IgG-positive cells >40%. The symptoms were markedly relieved following corticosteroid therapy. IgG4-related dacryoadenitis and sialadenitis (Mikulicz’s disease) with acquired hemophilia A (AHA) can also be seen in the pediatric population and should be considered a differential diagnosis in patients with relevant symptoms.