Major depressive disorder (MDD) is a significant psychiatric condition, with many affected individuals not gaining remission from conventional treatments, leading to classification as treatment-resistant depression (TRD). This study aimed to investigate the potential of intravenous (IV) ketamine, particularly the S-enantiomer esketamine in nasal spray form, for treating patients with TRD and associated comorbidities. We report three cases of patients with diverse psychiatric and medical backgrounds whom all reported significant symptomatic relief from depressive episodes and suicidal ideation (SI) following esketamine administration. Additionally, esketamine seemed to proffer benefits beyond the primary depressive symptoms, positively impacting other comorbid conditions, such as agitation, self-injurious behavior (SIB), and chronic pain. The goal of this paper is to highlight that while esketamine's primary utility is in addressing TRD, its therapeutic potential may extend to a variety of associated conditions. However, it is crucial to underscore the heterogeneity of MDD, emphasizing the necessity for individualized therapeutic approaches and further research into esketamine's broader applications.Full article

Practice guidelines recommend fixed combinations of calcipotriol, a topical vitamin D analogue, and betamethasone dipropionate, a high potency corticosteroid, as first line topical treatment for mild to moderate plaque psoriasis of the body and scalp. A new foaming lotion for treatment of Psoriasis was developed and patented by the Spanish Ministry of Industry, Trade and Tourism (Invention patent reference number 202030824). The foaming lotion is composed of clobetasol, papaverine hydrochloride, spironolactone, milk-peptide-complex and propylene glycol. Three cases with moderate Psoriasis aged 34, 36 and 66 years old were treated with our new foaming lotion for 7-8 days. The three patients reported important improvement in the itching sensations and remission of the scaled lesions. Before and after application of the new foaming lotion, Psoriasis Area Severity Index (PASI) scores improved in the first patient from 24.3 to 1.8, in the second patient from 26.1 to 1.8, and in the third patient from 27 to 1.8. Our results show the short-term effectiveness of the new foaming lotion in treating moderate and extensive Psoriasis. Long follow-up is needed to evaluate the remission period of Psoriasis and possible side effects of the new topical treatment.Full article

Anaphylaxis can be associated with hemodynamic shock, which requires the early initiation of adrenaline as part of its management. Cardiogenic pulmonary edema is a frequent entity in emergency services with increased mortality in patients with acute coronary syndrome. The case report presents the case of a 55-year-old male patient who entered the emergency department with a non-ST-segment elevation myocardial infarction (NSTEMI) associated to pulmonary edema and anaphylaxis. During his stay in the emergency room, he had an anaphylactic reaction to dipyrone (metamizole) used for pain control. The patient presented signs of acute pulmonary edema, a hypertensive urgency after the use of adrenaline for the management of anaphylaxis.  There was doubt as to whether the dyspnea was of anaphylactic or cardiogenic origin, so an emergency ultrasound was performed, which suggested a bilateral pattern B.  This allowed timely management of ventilatory failure with systemic nitrates, diuretics, and oxygen therapy, which controlled blood pressure and resolved ventilatory failure. Subsequently, he was transferred to an institution with a hemodynamic service for the management of NSTEMI. We highlight the utility of emergency ultrasonography for immediate decision-making and the low prevalence of anaphylactic reaction in a patient with NSTEMI leading to acute pulmonary edema.Full article

Pulsatile blood flow in a subject-specific human aortic arch and its major branches is studied computationally for a peak Reynolds number of 1553 and a Womersley number of 22.74. The aortic geometry is constructed from the CT-scan images of a subject. The aorta has out-of-plane curvature and significant area variation along the flow direction. A physiologically representative pulsatile velocity waveform is applied as boundary condition at the inlet of the aorta. The primary velocity profiles are skewed towards the inner wall of the ascending aorta during the entire cardiac cycle. In the decelerating phase, reverse flow is noted along the inner wall and the magnitude of maximum velocity is about 50 % of the peak flow condition. Flow separation is observed in the inner wall of the ascending aorta during the decelerating and reverse flow phases of the cardiac cycle. In the accelerating phase, however, flow separation does not occur. The major observation of the present work is the existence of complex and asymmetrical vortical flow structures which are not observed either in simple curved pipes or in idealized aortic arch computational studies. The relative strength of the secondary flow with respect to the primary flow is quantified by means of Relative Secondary Kinetic Energy whose highest value is evaluated to be 1.202 occurring near the entrance of the right carotid artery during the maximum reverse flow condition. High values of wall shear stress is observed at distal of the left and right subclavian arteries, the bifurcation of brachiocephalic artery between right subclavian artery and right carotid artery, and proximal inner wall of descending aorta during the cardiac cycle. The wall shear stress at the bifurcations of the branches are low and oscillatory and generally correlates with the preferential sites for atherosclerosis. The flow structures on the aorta wall are explicitly highlighted by the limiting streamlines. The application of limiting streamlines to clearly elucidate the complex on-wall flow structures is one of the key contributions of the present study. During the decelerating and reverse flow phases several critical points are observed on the aortic wall. These complex flow structures vanish during the accelerating phase. The observations made in the present study will be helpful in creating accurate and clinically useful computational models.Full article

This paper leverages gene and cell therapy research in diverse disorders ranging from monogenic to infectious diseases to cancer and emerging breakthroughs, where one can harness individual genes or a synthetic gene sequence designed based on a shared molecular pattern in infected cells to better fight various disorders [1]. A pivotal task is to predict the performances of candidate gene therapies to guide clinical translational research using methods such as retrospective bioinformatic analyses. Implementing them to a large-scale gene therapy database reveals that it is feasible to construct and apply well-performing interpretable, supervised learning models [2]. Preliminary evidence of machine learning approaches' statistical significance helps clinicians and biomedical researchers, market participants, and regulatory and economic experts derive relevant, practical applications, thereby enhancing the deployment of gene therapy and genomics to achieve positive, long-term growth for humanity while alleviating the ongoing worldwide economic burden precipitated by prolonged and recurring diseases. Deploying machine learning techniques to accelerate gene and cell therapy drug development and trials shall also mitigate the existing obstacle of limited patient access to emerging, transformative medical innovations such as gene therapy due to skyrocketing prices, which often herald gene therapy products as the world's most expensive medicines [3]. Moreover, in preventing patients from accessing effective, life-saving genetic medicines, there commonly exists a multidimensional access gap encompassing the availability, affordability, and quality or acceptability of these clinical treatments. The ensuing substantial gap has repeatedly been documented and mainly emanates from differential institutional and socio-political choices around resource allocation at international and domestic levels [4]. Particularly, it is also due to the stringent licensure and regulatory approval processes underpinned by insufficient evidence for novel safety and clinical efficacy profiles for genetic therapies in multiple micro-local diagnoses and subpopulations. We believe that a higher likelihood of gene therapy adoption shall result when the clinical evidence path contains adequate representation from the most diverse and relevant patient populations [5].Full article