Lysosomal exocytosis: From cell protection to protumoral functions.

Lysosomes are single membrane bounded group of acidic organelles that can be involved in a process called lysosomal exocytosis which leads to the extracellular release of their content. Lysosomal exocytosis is required for plasma membrane repair or remodeling events such as bone resorption, antigen presentation or mitosis, and for protection against toxic agents such as heavy metals. Recently, it has been showed that to fulfill this protective role, lysosomal exocytosis needs some autophagic proteins, in an autophagy-independent manner. In addition to these crucial physiological roles, lysosomal exocytosis plays a major protumoral role in various cancers. This effect is exerted through tumor microenvironment modifications, including extracellular matrix remodeling, acidosis, oncogenic and profibrogenic signals. This review provides a comprehensive overview of the different elements released in the microenvironment during lysosomal exocytosis, i.e. proteases, exosomes, and protons, and their effects in the context of tumor development and treatment.

Comparison of false starts by saw created on flesh and dry bones; as close as possible to the real conditions of criminal dismemberment.

In most experimental protocols, false starts are produced on dry bones obtained through a maceration process for anthropological analyses, for the sake of reproducibility. Although this allows for controlled experimental conditions, the absence of soft parts when experimentally creating false starts does not correspond to the real conditions of criminal dismemberment. The main objective of this study was to determine if the results of experimental work on the characteristics of false starts were valid under medico-legal conditions. In this experimental study, a hand saw (rip saw, wavy set, TPI 32) was used. 240 false starts were produced on human and pig bones. Randomly, the false starts were either produced on a dry bone or on a flesh bone. The criteria for microscopic analysis included the shape of the walls, the shape and visibility of striae on the floor, the shape of the profile, and the minimum width of the false start. On human bone, 100% of the false starts produced on a bone that had previously undergone a maceration process for anthropological analyses (dry bone) allowed the definition of all the blade characteristics. This was the case for 78.3% on bone in the presence of soft tissue (flesh bone). The striae on the floor of the false start are in some cases less visible with flesh bones, implying that it may be more difficult to conclude on the characteristics of a saw under medico-legal conditions.

Closed Rupture of the Extensor Hallucis Longus (EHL) Tendon Due to Forced Traumatic Hyperflexion of the Hallux: A Case Report.

A closed spontaneous rupture of the extensor hallucis longus (EHL) tendon is an infrequent yet challenging clinical occurrence, typically associated with systemic conditions (diabetes mellitus or rheumatoid arthritis). A closed EHL rupture, however, exists but is only reported as scattered cases in the literature. This article presents a unique case of a traumatic EHL tendon rupture in a patient without underlying predisposing factors. A 66-year-old woman, previously healthy, presented with an inability to dorsiflex her big toe following trauma, showcasing the clinical triad of pain, edema, and deficit in big toe extension. Magnetic resonance imaging confirmed a 5.9 cm EHL tendon gap that was treated by primary end-to-end repair of the ruptured tendon. The aim of this case report is to provide an overview of the literature available concerning the classification and treatment of EHL rupture and to assist in the early diagnosis and treatment of this rare condition.

A Comparison of Mini Open Transverse Incision and Longitudinal Incision for the Release of Moderate and Severe Carpal Tunnel Syndrome.

OBJECTIVES: Carpal tunnel syndrome is a common condition seen in daily clinical practice. Multiple minimally invasive techniques have emerged in the last decades for median nerve decompression. However, many research are needed to study the outcome on the patients and their safety profile. METHODS: We will compare group A that includes patients operated on using the minimally invasive transverse incision (number of patients = n = 221, females 76.7% and males 22.8%) versus group B that includes patients operated on using the longitudinal incision (n = 194, female 70.1% and male 29.9%) in term of clinical satisfaction and safety. The mean age of group A is 58.1±5.1 and that of group B is 58.8±4.8. The male and female distribution in both groups and the mean age were both similar with no statistically significant difference for the age (p = 0.79) or the gender distribution (p = 0.1). Data collected prospectively at regular intervals in time (preoperatively and at one month, three months, and six months post-carpal tunnel release (CTR)) between January 2006 and December 2021 were reviewed retrospectively. Patients' clinical findings, grip strength measurement using a hand dynamometer, and postoperative satisfaction measured using the BCTQ (Boston Carpal Tunnel Syndrome Questionnaire) scoring system were recorded and analyzed for each technique. RESULTS: A total of 415 patients were included in our study. All patients included had moderate to severe median nerve compression documented by nerve-conducted studies with positive Tinel's and Phalen's signs. Baseline demographics between group A (CTR through a longitudinal palmar mini-incision) and group B (CTR with a mini-transverse incision at the palmar crease) didn't show a statistically significant difference. Both groups showed improved grip strength and BCTQ scores at the post-operative follow-up. CONCLUSIONS: Median nerve decompression using both types of incisions has resulted in the same functional outcomes and patient satisfaction.

Aphid parasitism in winter wheat fields in a heterogeneous agricultural landscape.

The number, timing, and fitness of colonizing parasitoids in fields of ephemeral crops often depend on factors external to the fields. We investigated cereal aphid parasitism in 23 winter wheat fields using sentinel plants infested with bird cherry-oat aphids, Rhopalosiphum padi (L.) (Hemiptera: Aphididae), and we investigated the effect of parasitoids on cereal aphid population growth using exclusion and parasitoid-accessible cages infested with bird cherry-oat aphids. Lysiphlebus testaceipes (Cresson) (Hymenoptera: Braconidae), Aphelinus nigritus (Howard) (Hymenoptera: Aphelinidae), and Diaeretiella rapae (McIntosh) (Hymenoptera: Braconidae), in decreasing order of abundance, parasitized R. padi on sentinel plants. The mean percent parasitism in parasitoid-accessible cages was 5.2% in autumn and 35.0% in spring. Aphid population intensity was greater in complete exclusion than in parasitoid-accessible cages. Measures of landscape composition and configuration were quantified, and aphid parasitism in autumn by L. testaceipes and A. nigritus was positively associated with % landcover by summer crops and patch density. Parasitism by both species was negatively associated with contagion and % woodlands. Parasitism during spring was positively associated with % grassland and fractal dimension and negatively associated with % canola. The number of braconid mummies per sentinel plant was positively correlated to the number of braconid mummies on wheat stems from parasitoid-accessible cages. Results indicate that cereal aphid mortality caused by parasitoids and their ability to exert effective biological control is related to landscape structure. Comparing this study to an earlier study in the same agroecosystem demonstrated temporal stability of the landscape influence on aphid parasitism by L. testaceipes in winter wheat.

Autophagy markers are decreased in bone of osteoporotic patients: a monocentric comparative study.

BACKGROUND: Osteoporosis (OP) is a pathology characterized by bone fragility affecting 30% of postmenopausal women, mainly due to estrogen deprivation and increased oxidative stress. An autophagy involvement is suspected in OP pathogenesis but a definitive proof in humans remains to be obtained. METHODS: Postmenopausal women hospitalized for femoral neck fracture (OP group) or total hip replacement (Control group) were enrolled using very strict exclusion criteria. Western blot was used to analyze autophagy level. RESULTS: The protein expression level of the autophagosome marker LC3-II was significantly decreased in bone of OP patients relative to the control group. In addition, the protein expression of the hormonally upregulated neu-associated kinase (HUNK), which is upregulated by female hormones and promotes autophagy, was also significantly reduced in bone of the OP group. CONCLUSIONS: These results demonstrate for the first time that postmenopausal OP patients have a deficit in bone autophagy level and suggest that HUNK could be the factor linking estrogen loss and autophagy decline. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT03175874, 2/6/2017.

Dorsal Dislocation of the First and Second Metatarsophalangeal Joint: A Case Report and Literature Review.

Dorsal dislocation of the toes is an infrequent injury that can result in severe pain and deformity. Timely diagnosis and appropriate management are paramount for optimizing patient outcomes. This case report illustrates a 53-year-old male patient who suffered dorsal dislocation of the first and second metatarsophalangeal (MTP) joints due to a crush injury. We present the clinical manifestation, radiographic findings, and management approach for this unique isolated first and second ray MTP joint dorsal dislocation, without any associated fractures. This case report underscores several critical observations: firstly, hallux dorsal dislocation can potentially coincide with other injuries; secondly, it can stem from crushing trauma to the big toe; and thirdly, successful closed reduction, when followed by effective immobilization and early rehabilitation, can yield outstanding outcomes. Additionally, the report emphasizes the importance of pursuing another closed reduction attempt under general anesthesia, if the initial attempt in the emergency room proves unsuccessful, before contemplating open reduction.

Case Report and Literature Review: Lumbar Disc Extrusion Misdiagnosed as an Epidural Hematoma.

Accurate differentiation between epidural hematomas and lumbar disc extrusion is essential due to the potential overlap in clinical presentations. We present a case report highlighting a significant challenge in which a massive lumbar disc extrusion was mistaken for an epidural hematoma. This is a case report of a 38-year-old male patient who developed cauda equina syndrome four days after experiencing an audible cracking in the lower back during weightlifting activity. Magnetic resonance imaging (MRI) was inconclusive, unable to distinguish between an extruded nucleus pulposus and a spinal epidural hematoma. Subsequently, an urgent operation revealed a large herniated disc at the L4-L5 level, ruling out any hematoma. The patient's post-operative follow-up showed significant improvement, with almost complete recovery of motor and sensory functions. This case emphasizes the challenges faced when distinguishing between epidural hematomas and lumbar disc herniations, particularly on MRI. The lumbar disc herniation's substantial size, cranial and caudal migration on multiple levels, and signal intensity contributed to the misdiagnosis, underscoring the importance of careful interpretation and awareness of such complexities.

Neoadjuvant Radiation Therapy with Interdigitated High-Dose LRT for Voluminous High-Grade Soft-Tissue Sarcoma.

Purpose: To report a case of large extremity soft tissue sarcoma (2933 cc), safely treated with a novel approach of interdigitating high-dose LATTICE radiation therapy (LRT) with standard radiation therapy as a neoadjuvant treatment to surgery. Patients and Methods: Four sessions of high-dose LRT were delivered in a weekly interval, interdigitated with standard radiation therapy. The LRT plan consisted of 15 high-dose vertices receiving a dose >12 Gy per session, with 2-3 Gy to the peripheral margin of the tumor. The patient underwent surgical excision 2 months after the new regimen of induction radiation therapy. Results and Discussion: The patient tolerated the radiation therapy regimen well. The post-operative assessment revealed a negative surgical margin and over 95% necrosis of the total tumor volume. The post-surgical wound complication was mitigated by outpatient wound care. Interdigitating multiple sessions of high-dose LATTICE radiation treatments with standard neoadjuvant radiation therapy as a neoadjuvant therapy for soft tissue sarcoma was feasible and did not incur additional toxicity in this clinical case. A phase-I/II trial will be conducted to further evaluate the toxicity and efficacy of the new treatment strategy with the intent to increase the rate of pathologic necrosis, which has been shown to positively correlate with the overall survival.

Expanding horizons of reconstructive microsurgery in Lebanon: Reconstruction of complex traumatic wounds with anterolateral thigh perforator flaps in paediatrics patients less than 10 years of age.

Paediatric complex wounds pose a challenge to the reconstructive surgeon due to the intricacy of reconstructive options required. Developments in microsurgery and microsurgical technique have brought free tissue transfer ever closer to the comfort zone of the reconstructive surgeon for reconstruction of paediatric traumatic complex wounds. We present our experience of microsurgical reconstruction in Lebanon for complex traumatic wounds in paediatric patients under the age of 10 years using the free anterolateral thigh (ALT) flap. The ALT flap has proven its value as a safe, adaptable, and aesthetically acceptable reconstructive option in paediatric complex trauma.

Comparison of microscopic features of bone false starts produced by reciprocating saw blades and handsaws of the same class.

In cases of criminal dismemberment, the analysis of saw marks helps to determine the class of the saw used. The present study compared the microscopic features of experimental false starts performed on three freshly defleshed human femurs. 150 lesions were produced using three reciprocating blades and two hand saws of similar class. Two groups of tools were created according to the class of the blades: group 1 (teeth per inch = 6, alternating set) and group 2 (teeth per inch = 24, wavy set). The minimum width of the kerf was always thicker with reciprocating blades than that of the handsaw of the same class. This fact is linked to the thickness of the blades and not necessarily to the fast forth and back motion of the blades. Shape kerf profiles and shape of the walls were very confusing, with a lot of variation of the false starts caused by the reciprocating blades and the risk of misclassification (rip teeth versus crosscut teeth, alternating set versus wavy set). Striae on the kerf floor and bone islands were more consistent. The main conclusions are, first, that usual features of false starts achieved by reciprocating saw blades used in this work vary a great deal and may lead to misclassification of the saw class, and second, that no criterion has been found to differentiate reciprocating blades and handsaws. These results demonstrate that we have to be very prudent while estimating the possible saw from a false start in a real forensic case.

Rhinocerebral Mucormycosis: An Emerging Threat in the Era of COVID-19.

Mucormycosis is a rare but aggressive and fatal infection that is prevalent in immunocompromised patients. The variation in its clinical presentation and the lack of specificity are misleading and lead to a delay in the diagnosis and management. However, the era of coronavirus disease 2019 (COVID-19) is marked by the increasing emergence of Mucor infections, now identified as coronavirus-associated mucormycosis (CAM). Although many clinical forms exist, the most encountered in CAM is rhino-orbito-cerebral, as already reported in India. We present a case of a 56-year-old male patient with uncontrolled diabetes mellitus and a history of recent SARS-CoV-2 infection treated with IV steroids, presenting for maxillary teeth pain and instability on day 16 of COVID-19 infection. Early diagnosis of CAM is crucial and will help decrease mortality in COVID-19 patients, especially those with comorbidities such as diabetes mellitus. Increasing cases of CAM should prompt clinicians to have a high index of suspicion for rhinocerebral mucormycosis, especially in patients with risk factors receiving steroid therapy. In such patients, baseline glycosylated hemoglobin level and strict glycemic control by frequently measuring blood glucose levels and strictly adhering to insulin protocols would be rational but its efficacy in limiting the numbers of CAM in developing countries still needs to be confirmed.

Deeply Virtual Compton Scattering Cross Section at High Bjorken x_{B}.

We report high-precision measurements of the deeply virtual Compton scattering (DVCS) cross section at high values of the Bjorken variable x_{B}. DVCS is sensitive to the generalized parton distributions of the nucleon, which provide a three-dimensional description of its internal constituents. Using the exact analytic expression of the DVCS cross section for all possible polarization states of the initial and final electron and nucleon, and final state photon, we present the first experimental extraction of all four helicity-conserving Compton form factors (CFFs) of the nucleon as a function of x_{B}, while systematically including helicity flip amplitudes. In particular, the high accuracy of the present data demonstrates sensitivity to some very poorly known CFFs.

Parasite Viability as a Measure of In Vivo Drug Activity in Preclinical and Early Clinical Antimalarial Drug Assessment.

The rate at which parasitemia declines in a host after treatment with an antimalarial drug is a major metric for assessment of antimalarial drug activity in preclinical models and in early clinical trials. However, this metric does not distinguish between viable and nonviable parasites. Thus, enumeration of parasites may result in underestimation of drug activity for some compounds, potentially confounding its use as a metric for assessing antimalarial activity in vivo. Here, we report a study of the effect of artesunate on Plasmodium falciparum viability in humans and in mice. We first measured the drug effect in mice by estimating the decrease in parasite viability after treatment using two independent approaches to estimate viability. We demonstrate that, as previously reported in humans, parasite viability declines much faster after artesunate treatment than does the decline in parasitemia (termed parasite clearance). We also observed that artesunate kills parasites faster at higher concentrations, which is not discernible from the traditional parasite clearance curve and that each subsequent dose of artesunate maintains its killing effect. Furthermore, based on measures of parasite viability, we could accurately predict the in vivo recrudescence of infection. Finally, using pharmacometrics modeling, we show that the apparent differences in the antimalarial activity of artesunate in mice and humans are partly explained by differences in host removal of dead parasites in the two hosts. However, these differences, along with different pharmacokinetic profiles, do not fully account for the differences in activity. (This study has been registered with the Australian New Zealand Clinical Trials Registry under identifier ACTRN12617001394336.).

Chelating Polymers for Targeted Decontamination of Actinides: Application of PEI-MP to Hydroxyapatite-Th(IV).

In case of an incident in the nuclear industry or an act of war or terrorism, the dissemination of plutonium could contaminate the environment and, hence, humans. Human contamination mainly occurs via inhalation and/or wounding (and, less likely, ingestion). In such cases, plutonium, if soluble, reaches circulation, whereas the poorly soluble fraction (such as small colloids) is trapped in alveolar macrophages or remains at the site of wounding. Once in the blood, the plutonium is delivered to the liver and/or to the bone, particularly into its mineral part, mostly composed of hydroxyapatite. Countermeasures against plutonium exist and consist of intravenous injections or inhalation of diethylenetetraminepentaacetate salts. Their effectiveness is, however, mainly confined to the circulating soluble forms of plutonium. Furthermore, the short bioavailability of diethylenetetraminepentaacetate results in its rapid elimination. To overcome these limitations and to provide a complementary approach to this common therapy, we developed polymeric analogs to indirectly target the problematic retention sites. We present herein a first study regarding the decontamination abilities of polyethyleneimine methylcarboxylate (structural diethylenetetraminepentaacetate polymer analog) and polyethyleneimine methylphosphonate (phosphonate polymeric analog) directed against Th(IV), used here as a Pu(IV) surrogate, which was incorporated into hydroxyapatite used as a bone model. Our results suggest that polyethylenimine methylphosphonate could be a good candidate for powerful bone decontamination action.

Autophagy and bone diseases.

Autophagy is a ubiquitous cellular process, allowing the removal and recycling of damaged proteins and organelles. At the basal level, this process plays a role in quality control, thus participating in cellular homeostasis. Autophagy can also be induced by various stresses, such as nutrient deprivation or hypoxia, to allow the cell to survive until conditions improve. In recent years, the role of this process has been widely studied in many pathologies such as neurodegenerative diseases or cancers. In bone tissue, various studies have shown that autophagy is involved in the survival, differentiation and activity of osteoblasts, osteocytes and osteoclasts. The evolution of this knowledge has led to the identification of new molecular pathophysiological mechanisms in bone pathologies. This review reports the current state of knowledge on the role of autophagy in 4 bone diseases: osteoporosis, which seems to be associated with a decrease in autophagy, osteopetrosis and Paget's disease where the course of the autophagic process is disturbed, and finally osteosarcoma where autophagy seems to play a protumoral role. A better understanding of the involvement of autophagy in these pathologies should eventually lead to the identification of new potential therapeutic targets.

Deep Exclusive Electroproduction of π

We report measurements of the exclusive neutral pion electroproduction cross section off protons at large values of x_{B} (0.36, 0.48, and 0.60) and Q^{2} (3.1 to 8.4 GeV^{2}) obtained from Jefferson Lab Hall A experiment E12-06-014. The corresponding structure functions dσ_{T}/dt+εdσ_{L}/dt, dσ_{TT}/dt, dσ_{LT}/dt, and dσ_{LT^{'}}/dt are extracted as a function of the proton momentum transfer t-t_{min}. The results suggest the amplitude for transversely polarized virtual photons continues to dominate the cross section throughout this kinematic range. The data are well described by calculations based on transversity generalized parton distributions coupled to a helicity flip distribution amplitude of the pion, thus providing a unique way to probe the structure of the nucleon.

The stereomicroscope and scanning electron microscope comparison of false starts bones produced by an oscillating autopsy saw.

In forensic anthropology, saw mark analysis plays an important role in cases of criminal dismemberment. Autopsy saw is not used by the perpetrator in cases of dismemberment, but the forensic pathologist may accidentally create false starts with this saw during an autopsy, especially while sampling bones for further analysis, and these autopsy false starts can be confused with false starts produced by the offender. In this study, the characteristics of 20 false starts were compared using stereomicroscopy (SM) and scanning electron microscopy (SEM). These bone false starts were selected at random from a previous study of 100 false starts created by an electrical oscillating autopsy saw on human femoral bones. That study had enabled the categorization of the lesions into two groups ("superficial group" and "deep group") with a 0.52 mm depth cut off, based on the dramatic differences in lesion characteristics between these two groups. In the current study, SEM confirmed the characteristics of the false starts (walls and profile shapes, striae, bone islands and bone debris were studied), and above all explained the mechanism whereby oval bone islands in deep lesions are formed. Bone islands are due to the horizontal and vertical movement of the oscillating autopsy blade.