Nerve to subclavius for neurotization procedures: an anatomical feasibility study.

Injuries to the inferior trunk of the brachial plexus and its components can be debilitating. As such injuries are prioritized by surgeons during repair, an additional nerve transfer is considered herein. In the supine position, 13 adult cadavers (26 sides) underwent dissection of the nerve to subclavius and the proximal brachial plexus in the supraclavicular region. Once the nerve was located and isolated from origin to termination, measurements of its length and diameter were made. Next, the C8 and T1 roots and inferior trunk were identified. The distal end of the nerve to subclavius was transected and swung to these roots and the inferior trunk. Once the nerves to subclavius were transposed and in a tension-free manner, the length of excess nerve following being brought to each of these nerves was measured. A nerve to subclavius was identified on all sides. The nerve originated from the superior trunk and traveled anterior to the middle and inferior trunks on all sides. The mean diameter of the nerve to subclavius was 0.8 mm, and the mean length was 57 mm. After cutting the nerve to subclavius at its entrance into the subclavius muscle, the distal nerve could be transferred tension free to the inferior trunk of the brachial plexus and T1 ventral ramus on all sides. The distal nerve to subclavius reached the T1 ventral ramus with an average of 18 mm of additional length and to the C8 ventral ramus with an average of 19 mm. The nerve also could be transferred to the inferior trunk of the brachial plexus with an average of 20 mm of additional length. The nerve to subclavius was found to have approximately 3000 axons. To our knowledge, use of the nerve to subclavius has previously not been used for nerve transfer procedures. Based on our cadaveric study, this often-overlooked nerve can be easily transposed to other regional nerves such as the inferior trunk of the brachial plexus.

The Occipitalis Muscle as an Adjunct Superficial Landmark for the Transverse Sinus and Transverse-Sigmoid Junction: An Anatomical Study With Application to Posterior Cranial Fossa Surgery.

INTRODUCTION: Although neuronavigation systems are widely used for identifying deep intracranial structures, additional superficial anatomical landmarks can be useful when this technology is not available or is not working properly. Herein, we investigate the potential of the occipitalis muscle (OM), rarely mentioned in neurosurgical literature, as a superficial landmark for the transverse sinus (TS) and transverse-sigmoid sinus junction (TSJ). METHODS: Eighteen adult cadaveric heads underwent dissection. The borders of the OM were identified and measured. The muscle was then removed and the bone underlying the muscle was drilled. The relationships between the OM and the underlying dural venous sinuses were then investigated by using a surgical microscope. RESULTS: The OM is a quadrangular-shaped muscle, that invariably crosses the lambdoid suture, showing relationships with the TS inferiorly and the TSJ laterally. The medial border was located a mean of 2.7 cm from the midline and its lower edge was a mean of 1.6 cm above the TS. The inferior border was found between the lambdoid suture and the superior nuchal line in all the specimens. The medial half of the inferior margin was placed on average 1.1 cm superiorly to the TS while the lateral margin ran just above or over the TS. The lateral border was located a mean of 1.1 cm medially to the asterion and approximated the mastoid notch, being within 1-2 cm from it. The TSJ was between 2.1 and 3.4 cm lateral to OM lateral border. CONCLUSION: A combination of superficial anatomical landmarks can be useful for surgical planning. We found that the OM represents a valuable aide for neurosurgeons and is a reliable landmark for the deeper-lying TS and TSJ.

Anatomy and Histology of the Petrous Carotid Membrane: Application to Skull Base Surgery.

BACKGROUND: Published reports regarding the tissue types that surround the internal carotid artery (ICA) as it travels through the carotid canal vary. Reports have variably defined this membrane as periosteum, loose areolar tissue, or dura mater. With such discrepancies and realizing that knowledge of this tissue might be important for skull base surgeons who expose or mobilize the ICA at this location, the present anatomical/histological study was performed. METHODS: In 8 adult cadavers (16 sides), the contents of the carotid canal were evaluated; specifically, the membrane surrounding the petrous part of the ICA was studied, and its relationship to the deeper lying artery was observed. These specimens were stored in formalin and submitted for histological evaluation. RESULTS: Grossly, the membrane within the carotid canal traversed the entire carotid canal and was loosely adherent to the underlying petrous part of the ICA. Histologically, all membranes surrounding the petrous part of the ICA were consistent with dura mater. The dura mater of the carotid canal had an outer endosteal layer and an inner meningeal layer as well as a clear dural border cell layer in most specimens that approximated and was loosely applied to the adventitial layer of the petrous part of the ICA. CONCLUSIONS: The membrane that surrounds the petrous part of the ICA is dura mater. To our knowledge, this is the first histological investigation of this structure and thus serves to establish the true identity of this membrane and correct previous reports in the literature that have erroneously concluded that it is periosteum or loose areolar tissue.

Pectorobrachioepicondylaris musculoaponeurotic band: case description with evidence of median nerve compression.

Upper limb muscle variations can be encountered on imaging or at surgery. We report an unusual muscle and band found during routine dissection of the arm in a cadaver. This case is described and salient literature reviewed. A band was found that traveled from the insertion of the pectoralis major tendon distally and obliquely toward the medial intermuscular septum and medical epicondyle. Fibers of the brachialis were found to interdigitate into the band. A tunnel was formed that carried the median nerve and brachial vessels. Evidence of median nerve compression was observed. We considered this an example of a pectorobrachioepicondylaris muscle. However, some can lead to clinical presentations. Although the significance of the case reported herein is not certain, signs of median nerve compression were identified. We believe that the term pectorobrachioepicondylaris bests describes the muscle reported herein and that our case represents a previously unreported variant of this muscle.

The anatomy of the tendon of abductor pollicis longus and its morphological variations: An anatomical approach emphasizing the clinical relevance.

PURPOSE: The anatomical literature describes the abductor pollicis longus as a muscle with a single tendon inserting on the base of the first metacarpal bone, but investigations have shown that it often exhibits morphological variations. However, methodological approaches used to describe these variations have not been useful in a clinical context. Therefore, the purpose of this investigation was to study and relate such anatomical variations in a clinical context. BASIC PROCEDURES: Thirty upper limbs from the body donation program were dissected using standard procedures to identify the number of abductor pollicis longus (APL) tendons, their position, site of insertion, length, width and thickness. The presence or absence of the extensor pollicis brevis muscle was also noted. Inter and intra-observer reliability was analysed. MAIN FINDINGS: A total number of 71 tendons from the APL muscle were found in the thirty limbs. The most frequent distribution pattern was a main tendon inserted on the base of the first metacarpal and an accessory tendon inserted into the abductor pollicis brevis muscle. These tendons could divide into various tendinous slips that could insert in different locations. Also, clustering algorithms and classical statistical tests showed tendons inserting on the first metacarpal were longer than tendons not inserting on the first metacarpal (p = 0.03), while medial tendons and tendons from an APL muscle with supernumerary tendons were narrower (p < 0.001). The absence of the extensor pollicis brevis muscle was not related to the presence of supernumerary APL tendons. CONCLUSIONS: Radiological and surgical implications of these results are important when examining this region of the hand and wrist. The pathophysiology and treatment of de Quervain's tenosynovitis, trapeziometacarpal arthritis and trapeziometacarpal subluxation or laxity could be influenced by the results of our findings.

The sublingual branch of the lingual nerve: Anatomical study and suggestion for a new terminology.

The lingual nerve carries somatosensory fibers from the anterior two-thirds of tongue. The parasympathetic preganglionic fibers arising from the chorda tympani also travel with the lingual nerve in the infratemporal fossa to synapse in the submandibular ganglion to innervate the sublingual gland. However, only a few studies have investigated the specific nerve that innervates the sublingual gland and surrounding tissue i.e., the so-called sublingual nerve. Therefore, this study aimed to clarify the anatomy and definition of the sublingual nerves. Thirty sides from formalin fixed cadaveric hemiheads underwent microsurgical dissection of the sublingual nerves. The sublingual nerves were found on all sides and categorized into three branches, i.e., branches to the sublingual gland, branches to the mucosa of the floor of the mouth, and gingival branches. Additionally, branches to the sublingual gland were subcategorized into types I and II based on the origin of the sublingual nerve. We suggest that the lingual nerve branches should be categorized into five branches, i.e., branches to the isthmus of the fauces, sublingual nerves, lingual branches, posterior branch to the submandibular ganglion, and branches to the sublingual ganglion.

Pulmonary barotrauma in SCUBA diving-related fatalities: a histological and histomorphometric analysis.

Arterial gas embolism following pulmonary barotrauma occurs in 13-24% of cases of diving deaths. The study aimed to evaluate the usefulness of a histomorphometric digital analysis in the detection of air space over-distension due to pulmonary barotrauma. The study was performed on lung parenchyma specimens of 12 divers: six had died due to arterial gas embolism following pulmonary barotrauma (mean age at death of 54 years, range of 41-61 years), and six had drowned in saltwater without a diagnosis of pulmonary barotrauma (mean age at death of 54 years, range of 41-66 years) (positive controls). For negative controls, six cases of non-SCUBA divers (mean age of death of 42 years, range of 23-55 years) who died of intracerebral haemorrhage were evaluated. No significant differences were observed in the characteristics of the air spaces between control groups (positive and negative). However, differences were observed in the area occupied by air spaces and the percentage of air space area when we compared the case group to the controls (p < 0.01); and there was a slight difference in the maximum and minimum diameters of air space (p < 0.05). The mean area occupied by air spaces and the mean percentage of air space were the most useful for discriminating pulmonary barotrauma from other causes of death (100% sensitivity and 91.7% specificity). Based on our study, inclusion of an increased pattern of air spaces as a possible diagnostic criterion for pulmonary barotrauma would be useful in discerning the cause of diving death.

Percutaneous hallux valgus surgery: Anatomical study of its safety and effectiveness.

BACKGROUND AND HYPOTHESIS: Although percutaneous hallux valgus surgery is increasing in popularity, concerns about safety regarding neurovascular and tendinous structures remain. The first aim of this body-donor study was to evaluate the safety of three common percutaneous portals. Secondly, to evaluate percutaneous surgery effectiveness in completing adductor tendon release and first ray osteotomies. PATIENTS AND METHODS: Twenty body-donor feet were included and underwent three percutaneous procedures, which are commonly performed in combination: distal metatarsal osteotomy, proximal phalanx osteotomy and adductor tendon release. After surgery, the distance between surgical portals and relevant neurovascular structures was measured. Damage to this neurovascular structures, tendons or articular cartilage was noted. Completion of adductor tendon release and osteotomies was verified. RESULTS: The medial dorsal digital nerve of the hallux was damaged in two specimens. Mild peritendon damage was observed in two feet. The rest of neurovascular and tendinous structures were intact. No cartilage damage was observed. The distance between the adductor tenotomy portal and the lateral dorsal digital nerve of the hallux and the first dorsal metatarsal artery was 3.3mm (SD 1.4) and 2.4mm (SD 1.8), respectively. Complete adductor tenotomy was achieved in 14 feet. CONCLUSIONS: The structure with the highest risk of damage during percutaneous hallux valgus surgery is the medial dorsal digital nerve. The lateral dorsal digital nerve and the first dorsal metatarsal artery might be at risk due to the small distance to the adductor tendon release portal. A deep anatomical knowledge and a meticulous surgical technique are required to avoid lesions to neurovascular and tendinous structures. LEVEL OF EVIDENCE: V, Cadaveric study.

Towards the Search for Potential Biomarkers in Osteosarcoma: State-of-the-Art and Translational Expectations.

Osteosarcoma represents a rare cause of cancer in the general population, accounting for <1% of malignant neoplasms globally. Nonetheless, it represents the main cause of malignant bone neoplasm in children, adolescents and young adults under 20 years of age. It also presents another peak of incidence in people over 50 years of age and is associated with rheumatic diseases. Numerous environmental risk factors, such as bone diseases, genetics and a history of previous neoplasms, have been widely described in the literature, which allows monitoring a certain group of patients. Diagnosis requires numerous imaging tests that make it possible to stratify both the local involvement of the disease and its distant spread, which ominously determines the prognosis. Thanks to various clinical trials, the usefulness of different chemotherapy regimens, radiotherapy and surgical techniques with radical intent has now been demonstrated; these represent improvements in both prognosis and therapeutic approaches. Osteosarcoma patients should be evaluated in reference centres by multidisciplinary committees with extensive experience in proper management. Although numerous genetic and rheumatological diseases and risk factors have been described, the use of serological, genetic or other biomarkers has been limited in clinical practice compared to other neoplasms. This limits both the initial follow-up of these patients and screening in populations at risk. In addition, we cannot forget that the diagnosis is mainly based on the direct biopsy of the lesion and imaging tests, which illustrates the need to study new diagnostic alternatives. Therefore, the purpose of this study is to review the natural history of the disease and describe the main biomarkers, explaining their clinical uses, prognosis and limitations.

Targeting PTEN Regulation by Post Translational Modifications.

Phosphatidylinositol-3,4,5-triphosphate (PIP3) is a lipidic second messenger present at very low concentrations in resting normal cells. PIP3 levels, though, increase quickly and transiently after growth factor addition, upon activation of phosphatidylinositol 3-kinase (PI3-kinase). PIP3 is required for the activation of intracellular signaling pathways that induce cell proliferation, cell migration, and survival. Given the critical role of this second messenger for cellular responses, PIP3 levels must be tightly regulated. The lipid phosphatase PTEN (phosphatase and tensin-homolog in chromosome 10) is the phosphatase responsible for PIP3 dephosphorylation to PIP2. PTEN tumor suppressor is frequently inactivated in endometrium and prostate carcinomas, and also in glioblastoma, illustrating the contribution of elevated PIP3 levels for cancer development. PTEN biological activity can be modulated by heterozygous gene loss, gene mutation, and epigenetic or transcriptional alterations. In addition, PTEN can also be regulated by post-translational modifications. Acetylation, oxidation, phosphorylation, sumoylation, and ubiquitination can alter PTEN stability, cellular localization, or activity, highlighting the complexity of PTEN regulation. While current strategies to treat tumors exhibiting a deregulated PI3-kinase/PTEN axis have focused on PI3-kinase inhibition, a better understanding of PTEN post-translational modifications could provide new therapeutic strategies to restore PTEN action in PIP3-dependent tumors.

Perioperative Nursing as the Guiding Thread of a Prehabilitation Program.

Multimodal preoperative prehabilitation has been shown to be effective in improving the functional capacity of cancer patients, reducing postoperative complications and the length of hospital and ICU stay after surgery. The availability of prehabilitation units that gather all the professionals involved in patient care facilitates the development of integrated and patient-centered multimodal prehabilitation programs, as well as patient adherence. This article describes the process of creating a prehabilitation unit in our center and the role of perioperative nursing. Initially, the project was launched with the performance of a research study on prehabilitation for gastrointestinal cancer surgery. The results of this study encouraged us to continue the implementation of the unit. Progressively, multimodal prehabilitation programs focusing on each type of patient and surgery were developed. Currently, our prehabilitation unit is a care unit that has its own gym, which allows supervised training of cancer patients prior to surgery. Likewise, the evolution of perioperative nursing in the unit is described: from collaboration and assistance in the integral evaluation of the patient at the beginning to current work as a case manager; a task that has proven extremely important for the comprehensive and continuous care of the patient.

Fluctuations in AKT and PTEN Activity Are Linked by the E3 Ubiquitin Ligase cCBL.

3-Poly-phosphoinositides (PIP3) regulate cell survival, division, and migration. Both PI3-kinase (phosphoinositide-3-kinase) and PTEN (phosphatase and tensin-homolog in chromosome 10) control PIP3 levels, but the mechanisms connecting PI3-kinase and PTEN are unknown. Using non-transformed cells, the activation kinetics of PTEN and of the PIP3-effector AKT were examined after the addition of growth factors. Both epidermal growth factor and serum induced the early activation of AKT and the simultaneous inactivation of PTEN (at ~5 min). This PIP3/AKT peak was followed by a general reduction in AKT activity coincident with the recovery of PTEN phosphatase activity (at ~10-15 min). Subsequent AKT peaks and troughs followed. The fluctuation in AKT activity was linked to that of PTEN; PTEN reconstitution in PTEN-null cells restored AKT fluctuations, while PTEN depletion in control cells abrogated them. The analysis of PTEN activity fluctuations after the addition of growth factors showed its inactivation at ~5 min to be simultaneous with its transient ubiquitination, which was regulated by the ubiquitin E3 ligase cCBL (casitas B-lineage lymphoma proto-oncogene). Protein-protein interaction analysis revealed cCBL to be brought into the proximity of PTEN in a PI3-kinase-dependent manner. These results reveal a mechanism for PI3-kinase/PTEN crosstalk and suggest that cCBL could be new target in strategies designed to modulate PTEN activity in cancer.

Role of NRF2 in Lung Cancer.

The gene expression program induced by NRF2 transcription factor plays a critical role in cell defense responses against a broad variety of cellular stresses, most importantly oxidative stress. NRF2 stability is fine-tuned regulated by KEAP1, which drives its degradation in the absence of oxidative stress. In the context of cancer, NRF2 cytoprotective functions were initially linked to anti-oncogenic properties. However, in the last few decades, growing evidence indicates that NRF2 acts as a tumor driver, inducing metastasis and resistance to chemotherapy. Constitutive activation of NRF2 has been found to be frequent in several tumors, including some lung cancer sub-types and it has been associated to the maintenance of a malignant cell phenotype. This apparently contradictory effect of the NRF2/KEAP1 signaling pathway in cancer (cell protection against cancer versus pro-tumoral properties) has generated a great controversy about its functions in this disease. In this review, we will describe the molecular mechanism regulating this signaling pathway in physiological conditions and summarize the most important findings related to the role of NRF2/KEAP1 in lung cancer. The focus will be placed on NRF2 activation mechanisms, the implication of those in lung cancer progression and current therapeutic strategies directed at blocking NRF2 action.

Anatomic landmarks for a safe arthroscopic approach to the deep gluteal space: a cadaveric study / Hitos anatómicos para un abordaje artroscópico seguro del espacio glúteo profundo: un estudio cadavérico

SUMMARY: To determine the morphometric landmarks and anatomical variants relevant to the arthroscopic approach to the deep gluteal space. Twenty deep gluteal spaces from cadaveric specimens were dissected. The anatomical variants of the sciatic nerve (SN) were determined according to the Beaton and Anson classification. A morphometric study of the distances in the subgluteal space was carried out to define the anatomical references to achieve a safe arthroscopic approach for piriformis syndrome [GT-SN=Distance from greater trochanter (GT) to SN emergence; GT-IT=Distance from GT to ischial tuberosity (IT); GT-IGA=distance from GT to inferior gluteal artery (IGA) emergence; IT-SN=distance from IT to SN emergence; IT-IGA=distance from IT to IGA]. The SN showed the most frequent anatomical pattern with an undivided nerve coming out of the pelvis below the piriformis muscle (Beaton type A) in 16 specimens (80 %). The common peroneal nerve emergence in the subgluteal space through the piriformis muscle (PM) with the tibial nerve being located at the lower margin of the piriformis muscle (Beaton type B) was observed in 4 specimens (20 %). The morphometric measurements of the surgical area of study were: GT-SN=7.23 cm (±8.3); GT-IT=8.56 cm (±0.1); GT-IGA=8.46 cm (±0.97); IT-SN=5.28 cm (±0.73), IT- IGA=5.47 cm (±0.74). When planning surgery for the deep gluteal syndrome in adult patients, the fact that the emergence of the SN in the subgluteal space is approximately 7 cm from the greater trochanter and 5 cm from the ischial tuberosity must be considered.

RESUMEN: El objetivo del estudio fue determinar referentes morfométricos y variantes anatómicas relevantes en el abordaje artroscópico del espació subglúteo. Se disecaron veinte regiones glúteas procedentes de cadáver. Las variaciones anatómicas del nervio ciático (SN) se determinaron de acuerdo con la clasificación de Beaton y Anson. Se llevó a cabo un estudio morfométrico de distancias en el espacio subglúteo, con objeto de determinar referencias que permitan un abordaje artroscópico seguro del sindrome piriforme [GT-SN= distancia trocánter mayor (GT) a la emergencia del nervio ciático (SN); GT-IT= distancia GT a la tuberosidad isquiática (IT); GT-IGA= distancia GT a la emergen- cia de la arteria glútea inferior (IGA); IT-SN= distancia IT a la emergencia del SN; IT-IGA= distancia IT a la IGA]. El patrón más frecuente del SN fue su emergencia no dividida por el margen inferior del músculo piriforme (tipo A Beaton) en 16 especímenes (80 %). La salida del nervio fibular común a través del músculo piriforme (PM) con el nervio tibial localizado en el margen inferior del PM (tipo B Beaton) se observó en 4 especímenes (20 %). Las medidas en el área quirúrgica de estudio fueron: GT-SN= 7,23 cm ± 8,3; GT-IT= 8,56 cm ± 0,1; GT-IGA= 8,46 cm ± 0,97; IT-SN= 5,28 cm ± 0,73 IT-IGA= 5,47 cm ± 0,74. En la cirugía del síndrome glúteo profundo en adultos, debe considerarse que la sa- lida del SN hacia el espacio subglúteo tiene lugar aproximadamente a 7 cm del GT y a 5 cm de la IT.

A comparison of two designs of postoperative shoe for hallux valgus surgery: A biomechanical study in a cadaveric model.

BACKGROUND: Hallux Valgus Surgery success depends not only on the operative technique, but also on the care of the foot during the postoperative period. Orthopedic shoes have been developed to decrease the weight load on the first ray, an excess of which might lead to a loss of fixation or pseudoarthrosis. The goal of this study was to determine how the load distribution changed as the forced applied to the foot increased, with and without an orthopedic shoe. Also, we compared to different shoe models. METHODS: Pressure sensors were placed under the first metatarsal head and the heel of twenty specimens of fresh cadaveric adult feet. Two orthopedic shoes were chosen, a double padded (MS) and a reverse camber shoe (RCS). 10 kg loads were progressively applied, up to 60 kg. We first compared three instances: no shoe, MS and RCS. A secondary analysis comparing barefoot versus shoes was performed. A mean comparison was performed (ANOVA/T-student). RESULTS: The mean pressure of the heed and the first metatarsal showed that there were significant differences between groups (P < .005). The secondary analysis (no shoe vs orthopedic shoes) showed that the pressure without shoe was significantly higher than with any orthopedic shoe (P < .005). There were no statistically significant differences between models of shoes (P = .402). CONCLUSION: After a surgical procedure for hallux valgus fixation, postoperative shoes should be indicated to decrease the pressure on the first metatarsal head and heel in order to avoid an overload of the postoperative area. LEVEL OF EVIDENCE: Cadaveric study. Level V.

Functions of Nuclear Polyphosphoinositides.

Despite interest in phosphoinositide (PtdIns) kinases, such as PtdIns 3 kinases (PI3K), as targets for controlling plasma membrane PtdIns levels in disease, the PtdIns have another less well-known site of action in the cell nucleus.Recent studies show that PtdIns use a variety of strategies to alter DNA responses. Here, we provide an overview of these newly identified forms of gene expression control, which should be considered when studying the therapeutic use of PtdIns-directed compounds. As PI3K is one of the most important clinical targets in recent years, we will focus on two polyphosphoinositides, the PI3K substrate PtdIns(4,5)di-phosphate (PI4,5P2) and its product PtdIns(3,4,5)tri-phosphate (PI3,4,5P3).

The Opposing Roles of PIK3R1/p85α and PIK3R2/p85ß in Cancer.

Dysregulation of the PI3K/PTEN pathway is a frequent event in cancer, and PIK3CA and PTEN are the most commonly mutated genes after TP53. PIK3R1 is the predominant regulatory isoform of PI3K. PIK3R2 is an ubiquitous isoform that has been so far overlooked, but data from The Cancer Genome Atlas shows that increased expression of PIK3R2 is also frequent in cancer. In contrast to PIK3R1, which is a tumor-suppressor gene, PIK3R2 is an oncogene. We review here the opposing roles of PIK3R1 and PIK3R2 in cancer, the regulatory mechanisms that control PIK3R2 expression, and emerging therapeutic approaches targeting PIK3R2.

Chromatin regulation by Histone H4 acetylation at Lysine 16 during cell death and differentiation in the myeloid compartment.

Histone H4 acetylation at Lysine 16 (H4K16ac) is a key epigenetic mark involved in gene regulation, DNA repair and chromatin remodeling, and though it is known to be essential for embryonic development, its role during adult life is still poorly understood. Here we show that this lysine is massively hyperacetylated in peripheral neutrophils. Genome-wide mapping of H4K16ac in terminally differentiated blood cells, along with functional experiments, supported a role for this histone post-translational modification in the regulation of cell differentiation and apoptosis in the hematopoietic system. Furthermore, in neutrophils, H4K16ac was enriched at specific DNA repeats. These DNA regions presented an accessible chromatin conformation and were associated with the cleavage sites that generate the 50 kb DNA fragments during the first stages of programmed cell death. Our results thus suggest that H4K16ac plays a dual role in myeloid cells as it not only regulates differentiation and apoptosis, but it also exhibits a non-canonical structural role in poising chromatin for cleavage at an early stage of neutrophil cell death.

Diving-related fatalities: multidisciplinary, experience-based investigation.

To describe the technical characteristics of fatal diving mishaps and to elucidate the causes of death using a sequence analysis and a multidisciplinary investigation of diving-related fatalities. All cases of diving deaths recorded on the coast of Girona (Spain) between January 2009 and May 2018 were analyzed. Most data were obtained from the police technical reports and the forensic pathology service. Each accident was analyzed in order to identify the trigger, disabling agent, disabling injury, and cause of death. During the study period 25 diving-related fatalities were recorded. Most of the victims were males aged 50-69 years, and 11 were experienced divers. Almost all victims were using open-circuit SCUBA to breathe with compressed air as their sole gas supply. None of the victims were diving alone. The most common identified triggers included exertion, panic, buoyancy problems, disorientation and confusion. The main factors identified as disabling agents were rapid ascent, a cardiac incident, panic and entrapment. Asphyxia, lung over expansion, and myocardial ischemia were the most frequent disabling injuries. Finally, drowning represented the main cause of death, followed by arterial gas embolism and natural causes or internal diseases. A differential diagnosis, performed in the setting of a multidisciplinary investigation, is essential for elucidating the cause of death in diving-related fatalities. The proposed sequence analysis allows to clarify underlying problems in these cases and to identify risk factors and unsafe behaviors in diving.

The cell biology behind the oncogenic PIP3 lipids.

The different mechanisms of phosphoinositide 3-kinase (PI3K) activation in cancer as well as the events that result in PI3K pathway reactivation after patient treatment with PI3K inhibitors was discussed on October 15-17th, 2018, in the medieval town of Baeza (Universidad Internacional de Andalucía, Spain) at the workshop entitled 'The cell biology behind the oncogenic PIP3 lipids'. These topics and the data presented regarding cellular functions altered by PI3K deregulation, the cooperation of PI3K/PTEN mutations with other tumor drivers, and the lessons learned for PI3K-targeted therapy, are discussed below.