Rejected

There is an unmet need for novel therapeutic tools relieving chronic pain. Hydrogen sulfide (HS) is highly involved in pain processes; however, the development of ideal matrices for sulfide donor compounds remains a great pharmaceutical challenge. We aimed to establish a suitable transdermal therapeutic system (TTS) using the HS donor diallyl disulfide (DADS) as a model compound. After the preparation of DADS, its solubility was investigated in different liquid excipients (propylene glycol, polyethylene glycol, silicone oil) and its membrane diffusivity was assessed in silicone matrices of different compositions. Drug-releasing properties of DADS-containing patches with different silicone oil contents were determined with Franz and flow-through cells. We found a correlation between the liquid excipient content of the patch and the diffusion rate of DADS. DADS showed the best solubility in dimethyl silicone oil, and the diffusion constant was proportional to the amount of oil above the 3 m/m% threshold value. The 8-day-old patch showed a significantly lower, but better-regulated, drug release over time than the 4-day-old one. In conclusion, the silicone-based polymer matrix developed in this study is suitable for stable storage and optimal release of DADS, providing a good basis for a TTS applied in chronic pain.

Hyperimmunoglobulin D syndrome (HIDS) is a hereditary autoinflammatory disease characterized by recurrent inflammatory attacks with fever, abdominal pain, lymphadenopathy, aphthous stomatitis, and skin lesions. There are few reports on HIDS patients complicated with macrophage activation syndrome (MAS); however, to our knowledge, there is no case of HIDS with recurrent MAS attacks. We report two pediatric patients initially diagnosed as Kawasaki disease and systemic juvenile idiopathic arthritis presented with recurrent MAS episodes with prolonged fever, skin rash, hepatosplenomegaly, cervical lymphadenopathy, aphthous stomatitis, headache, pancytopenia, hyperferritinemia, and hypofibrinogenemia, finally diagnosed as HIDS with a documented homozygous MVK gene mutation. This is the first report on recurrent MAS attacks due to HIDS in pediatric patients who were successful treated with corticosteroids and anti-IL-1 therapies. Thus, clinicians should be vigilantly investigated signs of autoinflammatory diseases in patients with recurrent MAS attacks during their disease course, and HIDS should be considered an underlying disease for triggering recurrent MAS attacks. We have also reviewed the current literature regarding HIDS cases complicated with a MAS attack and summarized their demographic, treatment, and outcome characteristics. Key points • Hyperimmunoglobulin D syndrome should be considered in differential diagnosis in patients who experienced recurrent macrophage activation syndrome attacks.

Idiopathic generalized epilepsies (IGEs) represent 15-20% of all cases of epilepsy in children. This study explores predictors of long-term outcome in a sample of children with childhood absence epilepsy (CAE). The medical records of patients with CAE treated at a university paediatric hospital between 1995 and 2022 were systematically reviewed. Demographics and relevant clinical data, including electroencephalogram, brain imaging, and treatment outcome were extracted. Outcomes of interest included success in seizure control and seizure freedom after anti-seizure medication (ASM) discontinuation. An analysis of covariance using the diagnostic group as a confounder was performed on putative predictors. We included 106 children (age 16.5 ± 6.63 years) with CAE with a mean follow-up of 5 years. Seizure control was achieved in 98.1% (in 56.6% with one ASM). Headache and generalized tonic-clonic seizures (GTCS) were more frequent in children requiring more than one ASM ( 0.001 and 0.002, respectively). Of 65 who discontinued ASM, 54 (83%) remained seizure-free, while 11 (17%) relapsed (mean relapse time 9 months, range 0-18 months). Relapse was associated with GTCS ( 0.001) and number of ASM ( 0.002). A history of headache or of GTCS, along with the cumulative number of ASMs utilized, predicted seizure recurrence upon ASM discontinuation. Withdrawing ASM in patients with these characteristics requires special attention.

We report a case of recurrent pain attacks during romiplostim treatment in a woman with immune thrombocytopenia carrying a heterozygous MEFV mutation. Five months after starting treatment with romiplostim for immune thrombocytopenia, she was diagnosed with idiopathic pericarditis. She was switched to eltrombopag, but thrombocytopenia did not improve. Romiplostim was restarted 7 months later, although she then developed recurrent right hypochondrial pain. The pain typically occurred three days after the romiplostim injection and resolved two days later. She had never experienced such recurrent pain before starting romiplostim or after discontinuing it. Genetic analysis showed that she carried a heterozygous R202Q alteration in exon 2 of the MEFV gene. MEFV mutation is known to cause familial Mediterranean fever, which is characterized by symptoms such as recurrent fever, abdominal and chest pain, arthritis, and pericarditis. This case suggests that romiplostim has the potential to trigger recurrent pain/inflammation attacks in individuals with systemic inflammatory abnormalities.

Reversible splenial-lesion syndrome (RESLES) is a relatively rare and underrecognized clinical-imaging syndrome involving the splenium of the corpus callosum (SCC). RESLES can be caused by various etiologies.

This research was carried out to examine the effect of childbirth-related Internet use by pregnant women on fear of childbirth (FOC). The descriptive study was conducted with 350 pregnant women who applied to the Outpatient Polyclinic of Gynaecology and Obstetrics. Of the pregnant women who used the Internet, 72.9% did so to research information about childbirth. The pregnant women used the Internet mostly to obtain information about coping with labour pain (43.4%), the delivery process (46.9%), the needs list at delivery (39.4%), about C-section/epidural analgesia for labour (26.8%), and about the environment of the delivery room (25.7%). It was determined that there was a statistically significant difference ( < .05) between the delivery-related video viewing status of the pregnant women, the mean score of the W-DEQ Version A ( < .05), and the FOC was lower in those who watched videos about delivery.IMPACT STATEMENT Previous studies have shown that pregnant women frequently use the Internet as a source of information about childbirth. The findings of this study reveal that watching videos and listening to or reading the narrations significantly affected the FOC. Nurses who provide preconception and antenatal care should consider Internet use as a risk factor for FOC and should guide pregnant women to reliable sources.

Norepinephrine is a catecholamine neurotransmitter that has been extensively implicated in the neurobiology of major depressive disorder (MDD). An accumulating body of evidence indicates that investigations into the action of norepinephrine at the synaptic/receptor level hold high potential for a better understanding of MDD neuropathology and introduce possibilities for developing novel treatments for depression. In this review article, we discuss recent advances in depression neuropathology and the effects of antidepressant medications based on preclinical and clinical studies related to beta-adrenergic receptor subtypes. We also highlight a beta-3 adrenergic receptor-involved mechanism that promotes stress resilience, through which antidepressant efficacy is achieved in both rodent models for depression and patients with major depression-an alternative therapeutic strategy that is conceptually different from the typical therapeutic approach in which treatment efficacy is achieved by reversing pathological alterations rather than by enhancing a good mechanism such as natural resilience. Altogether, in this review, we systematically describe the role of beta-adrenergic receptors in depression and stress resilience and provide a new avenue for developing a conceptually innovative treatment for depression.

The aim of this study was to describe the factors affecting mid- and late aortic remodelling following TEVAR with PETTICOAT technique among patients with complicated acute or subacute type B aortic dissection.

The objective is to develop immediate release buccal films of Eletriptan Hydrobromide (EHBR) using hydroxypropyl methylcellulose (HPMC) E5. The buccal films have the ability to disintegrate rapidly and provide both systemic and local effects. The solvent casting method was employed to prepare the films and the central composite rotatable design (CCRD) model was used for film optimization. All the formulated films were characterized for physicochemical evaluation (Fourier transform infrared spectroscopy (FTIR), X-ray Diffraction (XRD), differential scanning calorimetry (DSC), and Scanning electron microscopy (SEM), in in-vitro, ex-vivo, and in-vivo drug release. The fabricated films were transparent, colorless, and evenly distributed. The FTIR spectra showed no chemical interaction between the drug and excipients. In in-vitro analysis, the film has the highest% drug release (102.61 ± 1.13), while a maximum of 92.87 ± 0.87% drug was diffused across the cellulose membrane having a pore size of 0.45 µm. In the ex-vivo study, drug diffusion across the goat mucosa was performed and 80.9% of the drug was released in 30 min. In-vivo results depict a mean half-life (t½) of 4.54 ± 0.18 h and a C of 128 ± 0.87 (ng/mL); T was achieved in 1 h. Furthermore, instability and histopathological studies buccal films were proven to be safe and act as an effective dosage form. In a nutshell, optimized and safe instant release EHBR buccal films were prepared that have the tendency to provide effect effectively.

Phedimus aizoon is native to east Asian countries that including China, Siberia, Korea, Mongolia, and Japan. In China, the plant is highly valued for use in folk medicine, for detoxification and analgesia, blood pressure, hemostasis, and used as an ornamental. In August 2021, a leaf spot and blight disease were observed on P. aizoon in a 120-ha field in Pizhou, Jiangsu Province, China where disease incidence reached 90%, and almost every leaf was withered. Early symptoms appeared as dark brown lesions on leaf margins that enlarged and coalesced to form large necrotic areas. In efforts to determine the cause of the disease, ten symptomatic leaves were randomly collected from ten different plants at the site. Diseased leaf pieces that measured 5 mm2 were disinfected in 75% ethyl alcohol for 30 s and 7% NaOCl for 60 s, rinsed three times in sterile distilled water, and placed on potato dextrose agar (PDA). Ten fungal isolates obtained by single-spore isolations were selected for further study. These isolates produced colonies that measured 70 to 82 mm in diameter after 7 days growth on PDA. Colonies were black to brown in color with gray-white aerial hyphae on their surfaces. The isolates produced conidia that were ovate to pear-shaped, brown to black in color, with 1 to 4 transverse septa and 0 to 1 oblique septa, smooth surfaced, parietal cells extending into the beak, and measured 10 to 35.5 × 5.0 to 12.5 μm. Conidiophores were brown, erect or curved, branched, with pronounced spore marks, and measured 7.5 to 37.5 × 2.5 to 5.0 μm. All ten fungal isolates were morphologically similar to Alternaria alternata (Simmons 2007). Two representative isolates FC01 and FC02 were used for molecular identification. The internal transcribed spacer (ITS) region, RNA polymerase second largest subunit (RPB2), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), translation elongation factor 1-alpha (TEF1), and Alternaria major allergen (Alt a 1) were amplified with the primers ITS4/ITS5, RPB2-5F2/RPB2-7CR (Khodaei and Arzanlou 2013), gpd1/gpd2, EF1-728F/EF1-986R (Nishikawa and Nakashima 2020) and Alt-for/Alt-rev (Woudenberg et al. 2015). The resulting sequences were deposited in GenBank (ITS, ON584560, ON564492; RPB2, ON729984, ON703241; GAPDH, ON652866, ON652867; TEF1, ON652868, ON652869; Alta1, ON652870, ON652871). Phylogenetic analyses showed 100% identity between FC01 and FC02 and the type strain CBS 916.96. Thus, the fungus was identified as A. alternata based on morphology and molecular analysis. Pathogenicity tests were done by spraying conidial suspensions containing 106 conidia per ml of A. alternata isolates FC01 and FC02 on leaves of five healthy P. aizoon plants, separately. Five control plants were sprayed with distilled water and both sets of plants covered with plastic bags and placed in a greenhouse maintained at 25⁰ C. Plastic bags were removed from plants after 48 h. Dark brown lesions developed on inoculated plants after 16 days and control plants remained symptomless. The pathogenicity tests were conducted three times. A. alternata was reisolated and identified based on morphological and molecular traits, thus fulfilling Koch's postulates. To our knowledge, this is the first report of A. alternata causing leaf blight on P. aizoon in China and worldwide. Based on the plant's medicinal value, further studies should be directed toward control of this disease.