Rejected

Graviola ( L.), a plant growing in tropical regions, has many names and a range of ethnomedicinal uses. The leaves are used to treat insomnia, diabetes, cystitis, and headaches, the crushed seeds have anthelmintic properties, and the fruits are used in the preparation of ice creams, candy, syrups, shakes, and other beverages. The key active components are believed to be annonaceous acetogenins, with more than 100 such compounds having been isolated from . The plant is also a source of a range of phenolic compounds, essential oils, alkaloids, flavonol triglycosides, and megastigmanes, together with various minerals, including Mg, Fe, Cu, K, and Ca. Its key phenolic compounds are rutin, kaempferol, and quercetin. This paper provides an overview of the current state of knowledge about the antioxidant properties of various graviola organs and their major constituents, based on a review of various electronic databases. However, few findings have been obtained from clinical trials, and few in vitro and animal studies suggest that graviola preparations have antioxidant properties; as such, the antioxidant potential of graviola, and its safety, remain unclear.

Regional anesthesia (RA) may improve patient-related outcomes, including decreased operative complications, shortened recovery times, and lower hospital readmission rates. More analyses are needed using a diverse set of databases to examine characteristics associated with the receipt of RA.

Oral lichen planus (OLP) is a chronic inflammatory disease of unknown etiology which affects the oral mucosa. OLP varies in its clinical features from a reticular form that is, in most cases, asymptomatic, to atrophic-erosive, and is accompanied by symptoms of burning sensation and pain followed by difficulty in eating. Given the fact that OLP is a disease of unknown etiology, the treatment is symptomatic and involves suppressing the signs and symptoms of the disease using various topical and systemic drugs. The first line of therapy for treating symptomatic OLP is topical corticosteroids, whereas systemic corticosteroids are used for treating persistent lesions that do not respond to local treatment. However, the lack of convincing evidence on the efficacy of previous therapies, including topical corticosteroids, and numerous side effects that have appeared over recent years has resulted in the emergence and development of new therapeutic options. Some of the therapies mentioned are tacrolimus, efalizumab, dapson, interferon, retinoic acid, photochemotherapy with psoralen and ultraviolet A rays (PUVA), aloe vera, antimalarials, antibiotics and others. These therapies only partially meet the properties of efficacy and safety of use, thus justifying the continuous search and testing of new treatment methods.

A woman in her late 70s with bilateral total hip arthroplasty (THA) presented with left hip pain arising immediately after the last THA procedure, progressively worsening. Clinically, a severe abductor insufficiency with Trendelenburg limp was observed. Moreover, symptomatic leg length discrepancy required a contralateral heel lift of 0.5 cm. She was previously managed conservatively without any clinical benefit. Radiographs showed a well-fixed uncemented straight, sitting proud stem. MRI showed a large abductor tear. A minimally invasive proximal advancement of the greater trochanter was planned to allow direct surgical repair of the abductor lesion. The patient made a good recovery, and 12 months after surgery, wire removal was performed. The patient gained significant improvements in hip function (Harris Hip Score from 52 to 89), full limp recovery and complete pain relief at 13 months follow-up from primary surgery.

This study aimed to determine distinguishing predictors and develop a clinical score to differentiate COVID-19 and common viral infections (influenza, respiratory syncytial virus (RSV), dengue, chikungunya (CKV), and zika (ZKV)). This retrospective study enrolled 549 adults (100 COVID-19, 100 dengue, 100 influenza, 100 RSV, 100 CKV, and 49 ZKV) during the period 2017-2020. CKV and ZKV infections had specific clinical features (i.e., arthralgia and rash); therefore, these diseases were excluded. Multiple binary logistic regression models were fitted to identify significant predictors, and two scores were developed differentiating influenza/RSV from COVID-19 (Flu-RSV/COVID) and dengue from COVID-19 (Dengue/COVID). The five independent predictors of influenza/RSV were age > 50 years, the presence of underlying disease, rhinorrhea, productive sputum, and lymphocyte count < 1000 cell/mm. Likewise, the five independent predictors of dengue were headache, myalgia, no cough, platelet count < 150,000/mm, and lymphocyte count < 1000 cell/mm. The Flu-RSV/COVID score (cut-off value of 4) demonstrated 88% sensitivity and specificity for predicting influenza/RSV (AUROC = 0.94). The Dengue/COVID score (cut-off value of 4) achieved 91% sensitivity and 94% specificity for differentiating dengue and COVID-19 (AUROC = 0.98). The Flu-RSV/COVID and Dengue/COVID scores had a high discriminative ability for differentiating influenza/RSV or dengue infection and COVID-19. The further validation of these scores is needed to ensure their utility in clinical practice.

Suspected optic disc swelling is a common presentation in children. The delineation between true optic disc swelling and pseudopapilloedema, its common masquerade, requires careful evaluation. A streamlined pathway is required to avoid unnecessary investigations.

Terminally differentiated keratinocytes are critical for epidermal function and surrounded by involucrin (IVL). Increased IVL expression is associated with a near selective sweep in European populations compared to African. This positive selection for increased IVL in the epidermis identifies human adaptation out-of-Africa. The functional significance is unclear. We hypothesize Ivl to modulate the environmentally sensitive Vitamin D receptor (Vdr) in the epidermis. We investigated Vdr activity in Ivl -/- and wild-type (WT) mice using vitamin D agonist (MC903) treatment and comprehensively determined the inflammatory response using single-cell RNA sequencing (scRNA-seq) and associated skin microbiome changes using 16S bacterial phylotyping. Vdr activity and target gene expression were reduced in Ivl -/- mouse skin, with decreased MC903-mediated skin inflammation and significant reductions in CD4+ T cells, basophils, macrophages, monocytes, and type II basal keratinocytes and increase in suprabasal keratinocytes. Coinciding with the dampened MC903-mediated inflammation, skin microbiota of Ivl -/- mice was more stable compared to WT mice, which exhibited a MC903-responsive increase in Bacteroidetes and decrease in Firmicutes. Together, our studies in Ivl -/- mice identify a functional role for Involucrin to positively impact Vdr activity and suggest an emerging IVL/VDR paradigm for adaptation in the human epidermis.

Biologic disease-modifying anti-rheumatic drugs (bDMARDs), including certolizumab pegol (CZP), are effective treatment options for the management of non-radiographic spondyloarthritis (nr-axSpA). In the absence of head-to-head comparisons in nr-axSpA, we conducted a systematic literature review (SLR) and indirect treatment comparison (ITC) to better understand the comparative efficacy of CZP vs. other bDMARDs.

A retrospective analysis of clinical data of 60 patients with primary empty sella (PES) was conducted to further improve the understanding of the disease.

Insomnia is a common condition that may be caused by or coexist with other medical or psychological illnesses. Nearly a quarter of a billion people across the globe suffer from insomnia frequently. Lemborexant, a dual orexin receptor antagonist, is a recently authorized hypnotic-based medication for insomnia. The purpose of this systematic review is to further investigate its efficacy and safety profile, with the primary goal of comparing the effects of two FDA-approved doses of lemborexant, 5 mg and 10 mg (LEM5 and LEM10, respectively).