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Category: Bunion; Midfoot/Forefoot Introduction/Purpose: The utility of Lateral soft tissue release (LSTR) in the setting of percutaneous Hallux Valgus (PHV) surgery is still debated. Our aim was to conduct a systematic review of the literature comparing the results of PHV surgery with and without LSTR in order to define the benefits and risks related to this procedure. Our hypotheses were that LSTR would 1) reduce the risk or recurrence of the deformity without increasing the risk of complication and 2) lead to an improved clinical outcome with greater radiological correction. Methods: This systematic review followed the PRISMA checklist and was prospectively registered in the Prospero database (CRD4202230). Pubmed, Embase, Cochrane Library and Scopus were used to identify clinical papers reporting results after PHV surgery. Studies were pooled in two categories: PHV with LSTR (Group 1 or G1) and PHV without LSTR (Group 2 or G2). Data regarding the study design, demographics, the surgical procedure and the clinical and radiological outcome were extracted and compared. The modified Coleman Methodology score (mCMS) was used to assess the quality of studies included. Results: Sixteen studies were selected (G1:594 feet;G2:553 feet). The sample size (p=0.11), sex distribution (p=0.57), length of follow-up (p=0.79), size of the incision (p=0.13) were comparable. Studies in G2 included a younger population (54+-6.3 vs 44.4+- 6.8 years;p=0.006), however age did not correlate with the clinical and radiological outcome (all p>0.05). The pooled proportion of complication in the two groups (27%, 95%CI 17-38 and 25%, 95%CI 12-37, respectively) and the pooled proportion of recurrence at a minimum 18-month follow-up (2%, 95%CI 0-3 and 2%, 95%CI 0-5, respectively) didn't differ (p=0.79 and p=0.70). The pre- (51.7+-10.6 and 45.8+-1.7 points;p=0.23) and post-operative AOFAS scores (89.4+-4.3 and 86.9+-3.2 points;p=0.16) and the pre-(HVA:29.7+-2.9 and 44.1+-26.8 degrees,p=0.23)(IMA:12.5+-4.2 and 14.1+-2.6 degrees;p=0.94) and post-operative radiological angles (HVA:12.1+-4.3 and 12.3+-2.3;p=0.47)(IMA:9.2+-2.2 and 7.9+-1.3;p=0.2) didn't differ in the two groups. The methodological quality of studies (mCMS: 68.7+-11 points in G1, 63.4+-14.3 points in G2;p=0.2) was similar in G1 and G2 Conclusion: Lateral soft tissue release during percutaneous HV surgery does not seem to improve the clinical and radiological outcome nor reduces the risk of recurrence of the deformity at a mean 4-year follow-up.

Most life scientists would agree that understanding how cellular processes work requires structural knowledge about the macromolecules involved. For example, deciphering the double-helical nature of DNA revealed essential aspects of how genetic information is stored, copied and repaired. Yet, being reductionist in nature, structural biology requires the purification of large amounts of macromolecules, often trimmed off larger functional units. The advent of cryogenic electron microscopy (cryo-EM) greatly facilitated the study of large, functional complexes and generally of samples that are hard to express, purify and/or crystallize. Nevertheless, cryo-EM still requires purification and thus visualization outside of the natural context in which macromolecules operate and coexist. Conversely, cell biologists have been imaging cells using a number of fast-evolving techniques that keep expanding their spatial and temporal reach, but always far from the resolution at which chemistry can be understood. Thus, structural and cell biology provide complementary, yet unconnected visions of the inner workings of cells. Here we discuss how the interplay between cryo-EM and cryo-electron tomography, as a connecting bridge to visualize macromolecules in situ, holds great promise to create comprehensive structural depictions of macromolecules as they interact in complex mixtures or, ultimately, inside the cell itself.

Abstract Background Protein-coding genes have been considered the functional part of the genome, although they represent only 2% of the genome. In contrast, more than 90% of the genome produces non-coding RNA (ncRNA), including antisense (AS) genes, a type of long non-coding genes (encoding transcripts > 200 nucleotides) located on the opposite strand of coding genes. Therefore, antisense RNA (asRNA) can be complementary to the counterpart sense RNA, supporting a regulatory role with potential pathogenic consequences, as their deregulation has been associated with cardiovascular disease, cancer, and diabetes. Results We performed an in-depth review of AS genes in Ensembl and evaluated the expression of AS genes in human liver by third-generation RNA sequencing methods. Currently, 1656 AS genes overlapping with 1556 sense genes have been identified in the human genome. Coding genes with antisense counterparts were significantly larger and had higher transcriptional activity than genes without antisense counterparts. RNA nanopore sequencing of 15 human livers identified 185 transcripts (55 novel) from 150 known AS genes, and 1316 transcripts from 807 sense genes, with 111 sense-antisense pairs. Sense transcripts showed higher expression than antisense transcripts. Remarkably, RNA nanopore sequencing of human livers identified 146 transcripts (67 novel) corresponding to 118 possible novel AS genes. Conclusion This study reveals the landscape of AS genes in the human genome and demonstrates the power of long-read RNA sequencing to identify novel transcripts and even novel AS genes, exploring the relationship between sense and AS gene expression as well.

The long interspersed element-1 (LINE-1, hereafter L1) retrotransposon has generated nearly one-third of the human genome and serves as an active source of genetic diversity and human disease1. L1 spreads through a mechanism termed target-primed reverse transcription, in which the encoded enzyme (ORF2p) nicks the target DNA to prime reverse transcription of its own or non-self RNAs2. Here we purified full-length L1 ORF2p and biochemically reconstituted robust target-primed reverse transcription with template RNA and target-site DNA. We report cryo-electron microscopy structures of the complete human L1 ORF2p bound to structured template RNAs and initiating cDNA synthesis. The template polyadenosine tract is recognized in a sequence-specific manner by five distinct domains. Among them, an RNA-binding domain bends the template backbone to allow engagement of an RNA hairpin stem with the L1 ORF2p C-terminal segment. Moreover, structure and biochemical reconstitutions demonstrate an unexpected target-site requirement: L1 ORF2p relies on upstream single-stranded DNA to position the adjacent duplex in the endonuclease active site for nicking of the longer DNA strand, with a single nick generating a staggered DNA break. Our research provides insights into the mechanism of ongoing transposition in the human genome and informs the engineering of retrotransposon proteins for gene therapy.

Structural studies aiming to visualize the interaction of Tau with microtubules (MTs) face several challenges, the main concerning the fact that Tau has multiple MT-interacting regions. In particular, the four (or three) pseudo-repeats of Tau bind to identical elements along the MT lattice but do it through non-identical residues. In addition, any given Tau molecule can use all its repeats or just one for its engagement with MTs. Finally, the binding of one Tau is not necessarily in register with respect to the next one. The mismatch in the MT and Tau repeats, therefore, challenges conventional modes of image analysis when visualizing these samples using cryo-electron microscopy. This commentary is dedicated to those challenges and ways to circumvent them while aiming for an atomic description of the Tau-tubulin interaction.

Abstract Introduction Self‐expanding Y‐metal stents (SEMS) are best suited lesions with involvement of the carina and proximal main bronchi; however, Y‐stents can be difficult to place. These difficulties guided us to develop a modification of the classic technique that addresses some of the challenges during positioning. We present the Y reverse technique for Y stent insertion using a combination of rigid and flexible bronchoscopy. Materials and Methods This retrospective study included 15 consecutive patients, suffering from tracheal‐carina‐lower main bronchi complex, hospitalized at the Thoracic Surgery Unit of the Vanvitelli University of Naples between October 2021 and October 2023. Inclusion criteria: patients in which the length of the stenosis of the right bronchi was greater than that of the left bronchi, advanced oncological conditions, severe respiratory failure; exclusion criteria: Karnofsky scale with

Background and objective: The depth of the prostate-specific antigen (PSA) decline after androgen receptor pathway inhibitor (ARPI) treatment combined with androgen deprivation therapy for patients with metastatic hormone-sensitive prostate cancer (mHSPC) may affect prognosis. The primary objective in our study was the correlation between the PSA response at 3 mo and radiologic progression-free survival (rPFS) at 24 mo. Three groups were defined according to the PSA decline: complete response (PSA ≤0.02 ng/ml), partial response (PSA >0.02 and ≤0.2 ng/ml), and incomplete response (PSA >0.2 ng/ml). Secondary objectives were correlation between the PSA response at 3 mo and overall survival, and the development of a model predicting complete PSA response. Methods: We conducted a retrospective multicenter study of patients with mHSPC treated with apalutamide from May 2018 to September 2023 registered in the Real-World Evidence APA registry across 20 centers. Key findings and limitations: We included 633 patients with mHSPC. The median age at diagnosis was 68 yr (interquartile range [IQR] 63–75) and median PSA was 16 ng/ml (IQR 7.5–64). Some 63% of the short had low-volume disease, 51% had de novo disease, 48% had recurrent disease. At 3 mo, 27% had a complete response, 42% a partial response, and 31% an incomplete response, with corresponding rRFS rates at 24 mo of 92%, 86%, and 63%. According to the predictive model, a complete PSA response at 3 mo was associated with the use of next-generation imaging and PSA

Abstract Background Osmotic Demyelination Syndrome (ODS) encompasses Central Pontine Myelinolysis and Extrapontine Myelinolysis, both of which are serious neurological conditions linked to the overly rapid correction of hyponatremia. Despite growing evidence, the exact etiology of ODS remains incompletely understood. The present paper describes two case studies, aiming to provide a comprehensive overview of the pathological findings and clinical outcomes associated with ODS. Case presentation Case #1. A 74-year-old woman was admitted to the emergency department following a head trauma caused by a loss of consciousness. Initial laboratory tests revealed severe hyponatremia (sodium level of 101 mmol/L) and hypokalemia (potassium level of 2.9 mmol/L). The patient underwent corrective therapy with saline and potassium chloride. Despite the correction of electrolyte imbalances, the patient developed a hyperintense lesion in the median portion of the pons on T2-fluid-attenuated inversion recovery (FLAIR) MRI sequence 14 days post-treatment, consistent with ODS. The patient’s condition deteriorated, leading to irreversible coma and status epilepticus, culminating in death 32 days after admission. Case #2. An 81-year-old woman with a medical history of hypothyroidism, hypertension, major depression, and stage 3 chronic kidney disease presented with mild gait disturbances. Subsequent testing revealed severe hyponatremia (sodium level of 100 mmol/L). Following an initial clinical improvement due to sodium correction, the patient’s condition worsened, with symptoms progressing to confusion, lethargy, and eventually, ODS. Dermatological manifestations, including blistering lesions and facial edema, appeared as the condition advanced. The patient succumbed to irreversible coma 47 days after admission. Conclusion ODS traditionally carried a poor prognosis, with high mortality rates and diagnoses often made postmortem. However, recent advances in understanding the pathophysiology, along with improvements in diagnostic techniques such as MRI and intensive care treatments, have led to earlier identification, treatment, and recognition of milder forms of the syndrome. Despite these advancements, ODS remains a critical condition with significant risks, particularly following the rapid correction of severe hyponatremia.

Crimean-Congo hemorrhagic fever (CCHF) is a tickborne disease caused by CCHF virus (CCHFV) (species Orthonairovirus haemorrhagiae, genus Orthonairovirus, family Nairoviridae, order Bunyavirales). Endemic in Africa, the Middle East, Asia, and [...]