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The nuclear pore complex (NPC) is the sole mediator of nucleocytoplasmic transport. Despite great advances in understanding its conserved core architecture, the peripheral regions can exhibit considerable variation within and between species. One such structure is the cage-like nuclear basket. Despite its crucial roles in mRNA surveillance and chromatin organization, an architectural understanding has remained elusive. Using in-cell cryo-electron tomography and subtomogram analysis, we explored the NPC's structural variations and the nuclear basket across fungi (yeast; S. cerevisiae), mammals (mouse; M. musculus), and protozoa (T. gondii). Using integrative structural modeling, we computed a model of the basket in yeast and mammals that revealed how a hub of nucleoporins (Nups) in the nuclear ring binds to basket-forming Mlp/Tpr proteins: the coiled-coil domains of Mlp/Tpr form the struts of the basket, while their unstructured termini constitute the basket distal densities, which potentially serve as a docking site for mRNA preprocessing before nucleocytoplasmic transport.

Primary hepatic leiomyosarcoma (PHL) is a rare malignant tumor, which originates from smooth muscles. The imaging features are nonspecific and the diagnosis is often delayed until the tumor reaches a large size, which leads often to a dismal prognosis. We report a case of a 46-year-old male patient who was complaining about abdominal pain for 2 months. The imaging revealed the presence of a large mass in the liver with adrenal and liver metastasis. Diagnosis of PHL was confirmed by histopathological and immunohistochemical examinations. In this case report, we review the epidemiological, clinical, and paraclinical aspects of the disease, as well as the treatment modalities.

Inflammatory pseudotumor (IP) is a rare type of benign tumor. Although initially identified in the lung, it has now been identified in a number of somatic and visceral sites, but mesenteric presentation is uncommon and has a variable clinical presentation. As inflammatory pseudotumor mimic malignancy both clinically and radiologically, the radiologist should be familiar with this entity. The only effective treatment is complete surgical resection. We present the case of a 55-year-old woman who presented with chronic abdominal pain and was diagnosed with a mesenteric inflammatory pseudotumor, in an attempt to illustrate the different imaging aspects of this benign condition in ultrasound, computed tomography and magnetic resonance imaging, and to simplify the description of these tumors.

Septo-optic dysplasia (SOD) is a rare congenital condition characterized by a triad of septum pellucidum dysgenesis, optic nerve hypoplasia, and hypothalamic-hypophyseal dysfunction. In some cases, additional brain anomalies such as schizencephaly can occur, leading to a more complex presentation known as septo-optic dysplasia plus (SOD+). This case report describes a 2-year-old boy presenting with delayed psychomotor development and visual impairment, ultimately diagnosed with SOD+.

Gastrointestinal duplication is an infrequent congenital disorder characterized by the presence of a muscular layer covered by mucosa. Gastric duplication cysts account for approximately 2%-9% of all gastrointestinal duplication cysts. The typical clinical presentation often includes symptoms such as epigastric pain, vomiting, and the presence of a palpable abdominal mass. However, these symptoms can overlap with more common conditions. Diagnostic confirmation usually necessitates additional imaging studies, and surgical intervention is the recommended treatment approach. In this case report, we present the case of a 9-year-old girl who presented with chronic abdominal pain and vomiting. Following a comprehensive evaluation, including a CT scan and various diagnostic tests, a diagnosis of gastric duplication cyst was established. The patient subsequently underwent a laparotomy procedure, during which the cyst was completely excised. Follow-up visits indicated an uneventful recovery, with complete resolution of all symptoms. The aim of this work is to report on the clinico-radiological aspects of gastric duplication cysts and their surgical treatment.

Nephroblastoma or Wilms' tumor is the most common malignant tumor of the kidney in the pediatric population. Metastasis is caused by hematogenous spread. The most common localizations in decreasing order of frequency are lymph nodes, lungs, and liver. The bone is very rarely affected. According to the literature, bone metastases have been described in the iliac bone, skull, and mandible. The vertebral localization was described in 3 cases only, the first 1 in 2009, and the 2 others in 2015 . The goal of our work is to report a very rare case of metastatic vertebral localization of a Wilms' tumor in relapse after treatment; and thus to underline the potential for vertebral and intracanal involvement in nephroblastoma.

Uterine rupture is a serious and potentially life-threatening complication. It is commonly a complication that happens in the third trimester of pregnancy. Its occurrence in early pregnancy is very rare. We report a case of a patient who presented with uterine rupture on a scarred uterus during the termination of pregnancy with misoprostol at 10 weeks' amenorrhea. In this case, we discuss the clinical warning signs, risk factors, and diagnostic methodology, and compare our approach with the literature.

IntroductionCardiac rehabilitation (CR) adherence and functional outcomes were measured after COVID-19 regulations reduced group sizes to one-on-one, modeling a natural experiment.MethodsA retrospective analysis using a natural experiment model measured participants in 12 weeks of CR during the 17 months before and after a COVID-19-related closure was conducted. The age, sex, race, ethnicity, and referral diagnoses of the pre-COVID-19 closure and post-COVID-19 closure groups were analyzed using a student's unpaired T-test. Adherence (completion rate of CR) and functional outcomes [change in six-minute walk test (6MWT)] were assessed between the two groups using unpaired two-tailed student T tests in GraphPad Prism and confidence intervals were calculated with the Baptista-Pike method.ResultsThere were 204 patients in the pre-COVID-19 group and 51 patients in the post-COVID-19 group, due to the smaller group sizes in the post-COVID-19 group, with no significant differences in baseline characteristics between the groups. The pre-COVID-19 group had a higher patient-to-provider ratio [2.8 patients/provider (SD 0.74)] relative to the post-COVID-19 group [0.4 patients/provider (SD 0.12); p

Primary hyperparathyroidism (PHPT), an endocrine disorder most commonly caused by parathyroid adenoma (PTA), manifests with a diverse array of symptoms, reflecting the multisystem impact of parathyroid hormone: nephrolithiasis, peptic ulcer disease, psychiatric disorders, muscle weakness, constipation, polyuria, pancreatitis, myalgia, and arthralgia. Rarely do these PTA attain a significant size. PHPT is usually diagnosed through biochemical tests, and radiological imaging characterizes the adenoma. Serum 25-hydroxyvitamin D levels are useful in explaining the large adenoma size. Here, we report a rare case of a 60-year-old female from Morocco who presented with marked dyspnea due to a giant PTA.

Abstract Over the last decades, cognitive neuroscience has identified a distributed set of brain regions that are critical for attention. Strong anatomical overlap with brain regions critical for oculomotor processes suggests a joint network for attention and eye movements. However, the role of this shared network in complex, naturalistic environments remains understudied. Here, we investigated eye movements in relation to (un)attended sentences of natural speech. Combining simultaneously recorded eye tracking and magnetoencephalographic data with temporal response functions, we show that gaze tracks attended speech, a phenomenon we termed ocular speech tracking. Ocular speech tracking even differentiates a target from a distractor in a multi-speaker context and is further related to intelligibility. Moreover, we provide evidence for its contribution to neural differences in speech processing, emphasizing the necessity to consider oculomotor activity in future research and in the interpretation of neural differences in auditory cognition.

ABSTRACTThe nuclear envelope (NE) separates translation and transcription and is the location of multiple functions, including chromatin organization and nucleocytoplasmic transport. The molecular basis for many of these functions have diverged between eukaryotic lineages. Trypanosoma brucei, a member of the early branching eukaryotic lineage Discoba, highlights many of these, including a distinct lamina and kinetochore composition. Here, we describe a cohort of proteins interacting with both the lamina and NPC, which we term lamina-associated proteins (LAPs). LAPs represent a diverse group of proteins, including two candidate NPC-anchoring pore membrane proteins (POMs) with architecture conserved with S. cerevisiae and H. sapiens, and additional peripheral components of the NPC. While many of the LAPs are Kinetoplastid specific, we also identified broadly conserved proteins, indicating an amalgam of divergence and conservation within the trypanosome NE proteome, highlighting the diversity of nuclear biology across the eukaryotes, increasing our understanding of eukaryotic and NPC evolution.

MRKH syndrome, or Mayer-Rokitansky-Küster-Hauser syndrome, a rare congenital disease, manifests as a complete or partial aplasia of the uterus and the vagina’s upper two-thirds with normal external genitalia and functioning ovaries. Mayer-Rokitansky-Küster-Hauser syndrome can occur in isolation (type I) or in conjunction with other congenital extragenital deformities affecting the kidneys, skeleton, heart, eyes, or auditory system (type II). The diagnosis of Mayer-Rokitansky-Küster-Hauser syndrome typically relies on imaging studies, with transabdominal ultrasonography serving as the primary modality. However, magnetic resonance imaging is considered the gold standard for detailed assessment of internal genital anatomy. We present the case of an 18-year-old woman without any notable medical history who exhibited primary amenorrhea. Mayer-Rokitansky-Küster-Hauser syndrome type II was suspected on pelvic ultrasound and subsequently confirmed via magnetic resonance imaging. The patient was provided with psychological assistance and planned for vaginoplasty.

Maldevelopment of the vagina and cervix is frequently accompanied by uterine aplasia or hypoplasia. Complete cervico-vaginal aplasia with a normally developing uterus is a very uncommon type of developmental failure. Failure to treat the condition can result in complications such as hematometra and hematosalpinx caused by the retrograde flow of blood into the fallopian tubes. In this case report, we describe the case of a 32-year-old woman experiencing cyclic abdominal pain and primary amenorrhea. The patient exhibited cervico-vaginal agenesis, with a functional uterus that was complicated by hematometra and bilateral hematosalpinx.

A total femoral approach for fenestrated-branched endovascular aortic aneurysm repair has been increasingly favored to minimize risks of aortic arch manipulation. We describe a novel technique to support the advancement of endovascular devices into a target vessel. Following catheterization of the intended target artery and deployment of the diameter-reducing ties, a Coda semi-compliant balloon (Cook Medical) is advanced and inflated immediately above the target artery. It is used as a support as the wire, catheter, or sheath “bounces” on the balloon, stabilizing the support wire to advance stent grafts, balloons, or sheaths into the downward renal or mesenteric vessels.

Plants have long been valued for their medicinal and nutritional contributions to human life. Anacyclus pyrethrum, a member of the Asteraceae family, has attracted increasing attention as a source of natural products with diverse applications. In this study, we explored the toxicity and pharmacological properties of the aqueous extract of A. pyrethrum (AEAP). The acute toxicity study involved groups of mice subjected to oral administration of varying doses of AEAP, with immediate post-administration observations to detect any signs of toxicity or mortality. Comprehensive biochemical and hematological analyses encompassed assessments of renal function. The pharmacological profile was assessed by evaluating antinociceptive, anxiolytic, and antidepressant effects, which were measured using the hot plate test, elevated plus maze, open field test, and forced swim test, respectively. Different doses (100, 200, 400, and 800 mg/kg) were administered to rats via gavage for this assessment. The results revealed that the acute toxicity demonstrated the safety of AEAP at the tested doses, with no observed mortality or significant alterations. Moreover, it revealed that AEAP possesses an LD50 value greater than 5000 mg/kg. The pharmacological properties of AEAP demonstrated anxiolytic and antidepressant activities at a dose of 200 mg/kg, while no antinociceptive effect was observed. These findings underscore the potential of A. pyrethrum as a natural source of bioactive compounds with therapeutic applications. Further research is needed to explore long-term and chronic effects for a comprehensive assessment.

Fibrous dysplasia is a rare non-hereditary congenital condition characterized by 2 main forms: monostotic and polyostotic. Monostotic is the more common form, while polyostotic, often associated with a syndrome, is rarer. The case presented involves a 10-year-old patient who was diagnosed with polyostotic fibrous dysplasia accompanied by an endocrinopathy. This report explores the clinical and radiological aspects of this condition based on the patient’s case.

To date, all major modes of monoclonal antibody therapy targeting SARS-CoV-2 have lost significant efficacy against the latest circulating variants. As SARS-CoV-2 omicron sublineages account for over 90% of COVID-19 infections, evasion of immune responses generated by vaccination or exposure to previous variants poses a significant challenge. A compelling new therapeutic strategy against SARS-CoV-2 is that of single-domain antibodies, termed nanobodies, which address certain limitations of monoclonal antibodies. Here, we demonstrate that our high-affinity nanobody repertoire, generated against wild-type SARS-CoV-2 spike protein (Mast et al., 2021), remains effective against variants of concern, including omicron BA.4/BA.5; a subset is predicted to counter resistance in emerging XBB and BQ.1.1 sublineages. Furthermore, we reveal the synergistic potential of nanobody cocktails in neutralizing emerging variants. Our study highlights the power of nanobody technology as a versatile therapeutic and diagnostic tool to combat rapidly evolving infectious diseases such as SARS-CoV-2.

Focal fibrocartilaginous dysplasia is an uncommon benign bone condition that predominantly affects children and typically leads to varus deformities in the proximal tibia. It was first described by Bell in 1985. The etiology remains unknown and the diagnosis is radiological; biopsy is not necessary. We present a case of a 2-year-old child who presented to our department for a right limb varus deformity caused by focal fibrocartilaginous dysplasia.

Dyke-Davidoff-Masson syndrome (DDMS) is a rare entity. Few cases have been described in the literature. It can be symptomatic or asymptomatic. The clinical signs are very varied. Imaging is the key to diagnosis. Calvarial thickening, enlargement sinus, and cerebral hemiatrophy are suggestive signs. It is a cause of cerebral hemiatrophy and epilepsy. We report the clinical and radiological signs of this syndrome through a case of an 8-year-old male child treated for epilepsy. The importance of our article is to report a case diagnosed at an early age (8 years). Most studies report cases diagnosed in adults. MRI revealed pathognomonic signs of Dyke-Davidoff-Masson syndrome.

Clear cell sarcoma of the kidney is the most frequently misdiagnosed renal tumor in children. We report the case of a 6-year-old boy with clear cell sarcoma of the kidney with an unusual presentation, including a primary tumor of the left kidney with metastasis in the homolateral psoas muscle. The renal tumor was revealed by abdominal mass without hematuria. In a review of the literature. Clear cell sarcoma of the kidney is most commonly associated with bone and lung metastases. Muscular metastasis at initial diagnosis has not previously been reported. This case represents an unusual metastatic pattern of clear cell sarcoma of the kidney. This also illustrates clear cell sarcoma of the kidney's ability to metastasize to other sites including the muscular. These tumors present a diagnostic challenge for the radiologist who should be aware of this entity to differentiate it from other renal tumors which are more frequent at this age. We aim to report the clinical, radiological features, and pathological presentation of this entity.

Hydatid disease is still endemic in several regions worldwide including Morocco, and is caused in most cases by the larval form of 2 species of the tapeworm Echinococcus: E. granulosus and E. multilocularis. Primary hydatid disease of the bone without systemic involvement is rare. The disease has a silent clinical evolution until it reaches complicated stages. Complications may include pathological fracture, neural deficit, infection, and fistulization of the abscess. Preoperative diagnosis is based on clinical history, imaging findings, and serological tests, which lack high sensitivity and specificity. Although the interpretation of imaging studies can prove to be very confusing because the bone changes evolve with time, and the nonspecificity of these findings often leads to a mistaken diagnosis. The diagnosis requires a high index of suspicion, especially in patients who reside in or travel to sheep-raising areas where hydatid disease is endemic. A high index of suspicion is necessary for the diagnosis, especially in patients that live in or travel to sheep-raising areas where hydatid disease is endemic. The treatment of choice remains surgical, following the principles of a locally malignant lesion. Chemotherapy (albendazole alone or in combination with praziquantel) is indicated when surgery is not possible or as an adjuvant treatment. The prognosis is often poor. We report the case of a 28-year-old woman with long-standing pain in the left hip joint in which the imaging findings were thought of as being either tuberculous or neoplastic. The result of a CT-guided biopsy concurred with an unexpected diagnosis of a hydatid cyst. This case highlights that in the absence of a high index of suspicion for echinococcal infection, the semblance of imaging findings of hydatid disease in the bone to those of other skeletal pathologies can lead to misinterpretation.

Nuclear pore complexes (NPCs) mediate the nucleocytoplasmic transport of macromolecules. Here we provide a structure of the isolated yeast NPC in which the inner ring is resolved by cryo-EM at sub-nanometer resolution to show how flexible connectors tie together different structural and functional layers. These connectors may be targets for phosphorylation and regulated disassembly in cells with an open mitosis. Moreover, some nucleoporin pairs and transport factors have similar interaction motifs, which suggests an evolutionary and mechanistic link between assembly and transport. We provide evidence for three major NPC variants that may foreshadow functional specializations at the nuclear periphery. Cryo-electron tomography extended these studies, providing a model of the in situ NPC with a radially expanded inner ring. Our comprehensive model reveals features of the nuclear basket and central transporter, suggests a role for the lumenal Pom152 ring in restricting dilation, and highlights structural plasticity that may be required for transport.

The escalating rates of morbidity and mortality associated with opioid use disorder (OUD) have spurred a critical need for improved treatment outcomes. This study aimed to investigate the impact of prolonged exposure to Fentanyl, a potent opioid, on behavior, biochemical markers, oxidative stress, and the composition of the gut microbiome. Additionally, we sought to explore the therapeutic potential of Anacyclus pyrethrum in mitigating the adverse effects of Fentanyl withdrawal. The study unveiled that chronic Fentanyl administration induced a withdrawal syndrome characterized by elevated cortisol levels (12.09 mg/mL, compared to 6.3 mg/mL for the control group). This was accompanied by heightened anxiety, indicated by a reduction in time spent and entries made into the open arm in the Elevated Plus Maze Test, as well as depressive-like behaviors, manifested through increased immobility time in the Forced Swim Test. Additionally, Fentanyl exposure correlated with decreased gut microbiome density and diversity, coupled with heightened oxidative stress levels, evidenced by elevated malondialdehyde (MDA) and reduced levels of catalase (CAT) and superoxide dismutase (SOD). However, both post- and co-administration of A. pyrethrum exhibited substantial improvements in these adverse effects, effectively alleviating symptoms associated with OUD withdrawal syndrome and eliciting positive influences on gut microbiota. In conclusion, this research underscores the therapeutic potential of A. pyrethrum in managing Fentanyl withdrawal symptoms. The findings indicate promising effects in alleviating behavioral impairments, reducing stress, restoring gut microbiota, and mitigating oxidative stress, offering valuable insights for addressing the challenges of OUD treatment.

Burkitt’s lymphoma is rare but highly aggressive and very fast-growing B-cell non-Hodgkin’s lymphoma (NHL). It can affect any organ such as the central nervous system, jaw, intestines, kidneys, ovaries, and other organs. It results from the malignant evolution and proliferation of B-type lymphoid cells. The diagnosis is based on a biopsy of a tumor mass or bone marrow aspiration revealing the presence of tumor cells. We report the case of a 7 year old child who was referred for a gingival swelling evolving since 1 month following a dental extraction. Imaging and anatomopathological examination after biopsy concludes to a multi systemic Burkitt’s lymphoma. A chemotherapy was immediately started with spectacular complete remission.

Poland syndrome is indeed a rare congenital malformation that can present with various degrees of thoracic and homolateral upper limb anomalies. The classic features of Poland syndrome include agenesis or hypoplasia of the sternocostal head of the pectoralis major muscle, hypoplasia of the nipple, absence of subcutaneous fat, multiple rib abnormalities, and sometimes Sprengel deformity (elevation of the scapula). Additionally, ipsilateral symbrachydactyly (combination of “short fingers” with cutaneous syndactyly [fused fingers]) may also be observed. However, it’s important to note that not all of these findings are always present in every patient, and the combination of features can vary greatly. Surgical treatment for Poland syndrome primarily focuses on improving pulmonary functions resulting from severe thoracic deformities. However, it is frequently performed with the additional goal of enhancing cosmetic appearance. In recent times, the use of adipose-derived mesenchymal stem cells and fat transfer has shown promising results for correcting chest defects and breast augmentation. In our study, we present a series of 3 cases that were referred to our institution due to thoracic deformities associated with Poland syndrome.

[Figure: see text].

Abstract Cancer cells exhibit elevated lipid synthesis. In breast and other cancer types, genes involved in lipid production are highly upregulated, but the mechanisms that control their expression remain poorly understood. Using integrated transcriptomic, lipidomic, and molecular studies, here we report that DAXX is a regulator of oncogenic lipogenesis. DAXX depletion attenuates, while its overexpression enhances, lipogenic gene expression, lipogenesis, and tumor growth. Mechanistically, DAXX interacts with SREBP1 and SREBP2 and activates SREBP-mediated transcription. DAXX associates with lipogenic gene promoters through SREBPs. Underscoring the critical roles for the DAXX-SREBP interaction for lipogenesis, SREBP2 knockdown attenuates tumor growth in cells with DAXX overexpression, and DAXX mutants unable to bind SREBP1/2 have weakened activity in promoting lipogenesis and tumor growth. Remarkably, a DAXX mutant deficient of SUMO-binding fails to activate SREBP1/2 and lipogenesis due to impaired SREBP binding and chromatin recruitment and is defective of stimulating tumorigenesis. Hence, DAXX’s SUMO-binding activity is critical to oncogenic lipogenesis. Notably, a peptide corresponding to DAXX’s C-terminal SUMO-interacting motif (SIM2) is cell-membrane permeable, disrupts the DAXX-SREBP1/2 interactions, and inhibits lipogenesis and tumor growth. These results establish DAXX as a regulator of lipogenesis and a potential therapeutic target for cancer therapy.

Abstract Background The use of herbal medicines (medicinal plants or phytotherapy) has recently gained popularity in Europe and the United States. Nevertheless the exact mechanism of the preventive effects of these products is still far to be clearly established, being its knowledge necessary to successfully apply these therapies to avoid stone formation. Methods The effect of oral lemon juice administration on calcium oxalate urolithiasis was studied in male Wistar rats. Rats were rendered nephrolithic by providing drinking water containing 0.75% ethylene glycol [v/v] (EG) and 2% ammonium chloride [w/v] (AC) for 10 days. In addition to EG/AC treatment, three groups of rats were also gavage-administered solutions containing 100%, 75% or 50% lemon juice [v/v] (6 μl solution/g body weight). Positive control rats were treated with EG/AC but not lemon juice. Negative control rats were provided with normal drinking water, and were administered normal water by gavage. Each group contained 6 rats. After 10 days, serum samples were collected for analysis, the left kidney was removed and assessed for calcium levels using flame spectroscopy, and the right kidney was sectioned for histopathological analysis using light microscopy. Results Analysis showed that the rats treated with EG/AC alone had higher amounts of calcium in the kidneys compared to negative control rats. This EG/AC-induced increase in kidney calcium levels was inhibited by the administration of lemon juice. Histology showed that rats treated with EG/AC alone had large deposits of calcium oxalate crystals in all parts of the kidney, and that such deposits were not present in rats also treated with either 100% or 75% lemon juice. Conclusion These data suggest that lemon juice has a protective activity against urolithiasis.

An alarming rise in antimicrobial resistance worldwide has spurred efforts into the search for alternatives to antibiotic treatments. The use of bacteriophages, bacterial viruses harmless to humans, represents a promising approach with potential to treat bacterial infections (phage therapy). Recent advances in microscopy-based single-cell techniques have allowed researchers to develop new quantitative methodologies for assessing the interactions between bacteria and phages, especially the ability of phages to eradicate bacterial pathogen populations and to modulate growth of both commensal and pathogen populations. Here we combine droplet microfluidics with fluorescence time-lapse microscopy to characterize the growth and lysis dynamics of the bacterium Escherichia coli confined in droplets when challenged with phage. We investigated phages that promote lysis of infected E. coli cells, specifically, a phage species with DNA genome, T7 (Escherichia virus T7) and two phage species with RNA genomes, MS2 (Emesvirus zinderi) and Qβ (Qubevirus durum). Our microfluidic trapping device generated and immobilized picoliter-sized droplets, enabling stable imaging of bacterial growth and lysis in a temperature-controlled setup. Temporal information on bacterial population size was recorded for up to 25 h, allowing us to determine growth rates of bacterial populations and helping us uncover the extent and speed of phage infection. In the long-term, the development of novel microfluidic single-cell and population-level approaches will expedite research towards fundamental understanding of the genetic and molecular basis of rapid phage-induced lysis and eco-evolutionary aspects of bacteria-phage dynamics, and ultimately help identify key factors influencing the success of phage therapy.

Hydatid cyst disease is a health problem in some developing countries occurring in groups with permanent contact with dogs. It is a parasitic disease caused by Echinococcus Granulosus. The liver is the most common organ infected. If not treated appropriately; it may lead to developing life-threatening complications. Its rupture into bile ducts is the most frequent one, while hepatopulmonary fistula is a rare complication. We discuss the case of a child presenting those 2 complications as we emphasize the importance of early diagnosis and the role of the radiologist.

Abstract Background Pregnancy in patients with lipoprotein lipase deficiency is associated with high risk of maternal pancreatitis and fetal death. A very low fat diet (< 10% of calories) is the primary treatment modality for the prevention of acute pancreatitis, a rare but potentially serious complication of severe hypertriglyceridemia. Since pregnancy can exacerbate hypertriglyceridemia in the genetic absence of lipoprotein lipase, a further reduction of dietary fat intake to < 1–2% of total caloric intake may be required during the pregnancy, along with the administration of a fibrate. It is uncertain if essential fatty acid deficiency will develop in the mother and fetus with this extremely low fat diet, or whether fibrates will cross the placenta and concentrate in the fetus. Case presentation A 23 year-old gravida 1 woman with primary lipoprotein lipase deficiency was seen at 7 weeks of gestation in the Lipid Clinic for management of severe hypertriglyceridemia that had worsened with pregnancy. While on her habitual fat intake of 10% of total calories, her pregnancy resulted in an exacerbation of the hypertriglyceridemia, which prompted further restriction of fat intake to < 2% of total calories, as well as administration of gemfibrozil at a lower than average dose. The level of gemfibrozil, as the active metabolite, in the venous and arterial fetal cord blood was within the expected therapeutic range for adults. The clinical signs and a biomarker of essential fatty acid deficiency, namely the ratio of 20:3 [n-9] to 20:4 [n-6] fatty acids, were closely monitored throughout her pregnancy. Despite her extremely low fat diet, the levels of essential fatty acids measured in the mother and in the fetal blood immediately postpartum were normal. Normal essential fatty acid levels may have been achieved by the topical application of sunflower oil. Conclusions An extremely low fat diet in combination with topical sunflower oil and gemfibrozil administration was safely implemented in pregnancy associated with the severe hypertriglyceridemia of lipoprotein lipase deficiency.

Exocyst is an evolutionarily conserved hetero-octameric tethering complex that plays a variety of roles in membrane trafficking, including exocytosis, endocytosis, autophagy, cell polarization, cytokinesis, pathogen invasion, and metastasis. Exocyst serves as a platform for interactions between the Rab, Rho, and Ral small GTPases, SNARE proteins, and Sec1/Munc18 regulators that coordinate spatial and temporal fidelity of membrane fusion. However, its mechanism is poorly described at the molecular level. Here, we determine the molecular architecture of the yeast exocyst complex by an integrative approach, based on a 3D density map from negative-stain electron microscopy (EM) at ~16 Å resolution, 434 disuccinimidyl suberate and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride cross-links from chemical-crosslinking mass spectrometry, and partial atomic models of the eight subunits. The integrative structure is validated by a previously determined cryo-EM structure, cross-links, and distances from in vivo fluorescence microscopy. Our subunit configuration is consistent with the cryo-EM structure, except for Sec5. While not observed in the cryo-EM map, the integrative model localizes the N-terminal half of Sec3 near the Sec6 subunit. Limited proteolysis experiments suggest that the conformation of Exo70 is dynamic, which may have functional implications for SNARE and membrane interactions. This study illustrates how integrative modeling based on varied low-resolution structural data can inform biologically relevant hypotheses, even in the absence of high-resolution data.

The transformative potential of blockchain technology has resulted in its widespread adoption, bringing about numerous advantages such as enhanced data integrity, transparency, and decentralization. Blockchain has effectively proven its ability to establish trustworthy systems across a multitude of applications. As the number of transactions recorded into a blockchain grows, the blockchain’s size expands significantly, posing challenges to the network, particularly in terms of storage capacity and processing power. To address this problem, we present a cryptosystem based on RSA to provide aggregate signatures in blockchains. The aggregate signature replaces all transaction signatures of a block. In this scheme, all participating blockchain nodes use the same modulus $N$ , each with its own private and public key pair generated from $N$ . Regardless of the number of transactions, nodes, and signers, the aggregate signature size is always $O(k)$ , where $k$ is a security parameter. The miner that constructs a candidate block computes the aggregate signature $\sigma $ , replaces all transaction signatures by $\sigma $ , and transmits the block with only one aggregate signature. The proposed scheme incorporates a flexible and accountable subgroup aggregate signature mechanism, allowing any subset $t$ of $n$ total elements to sign data, where $t$ is the required number of signers. To verify that a set of elements signed the block, the verifier requires the aggregate signature, the aggregate public key, and the data hash. This approach requires minimal interaction between the signers, which results in reduced network traffic. Regardless of the network size, there are always $t + n$ exchanged messages. Experimental analysis shows the proposed aggregate signature scheme’s effectiveness in increasing security robustness and reducing block size and overall network traffic.

Abstract The optimal use of erythropoiesis-stimulating agents (ESAs) and parenteral iron in managing anemia in end-stage renal disease (ESRD) remains controversial. One-size-fits-all rule-based algorithms dominate dosing protocols for ESA and parenteral iron. However, the Food & Drug Administration (FDA) guidelines for using ESAs in chronic kidney disease recommend individualized therapy for the patient. This prospective quality assurance project was at a single hemodialysis (HD) center comprising three 6-month phases (A, B, C) separated by 3-month washout periods. Standard bi-weekly ESA dose titration and intravenous (IV) iron sucrose protocols were used in baseline Phase A, and ferric pyrophosphate citrate (FPC) augmented iron in Phase B. In Phase C, an FPC protocol and weekly, individualized ESA management were used. We examined clinic-level mean differences in hemoglobin (Hb) and ESRD-related outcomes by phase with repeated ANOVA. To examine the Hb at the patient level, we used multi-level mixed-effect regression adjusting for phase, month, and other relevant confounders at each month over time to derive the mean marginal effects of phase. There were 54, 78, and 66 patients in phases A, B, and C, respectively, with raw mean Hb values of 9.9, 10.2, and 10.3 g/dL. The percentage of Hb values

This study aims to evaluate the anticonvulsant effect of the aqueous extract of Rhus pentaphylla and Cuminum cyminum (300 mg/kg), orally, 45 min before intrahippocampal injection of kainic acid (1 µg/µL). The scoring of seizure severity, latency of seizures and duration of total seizures were recorded in 90 min. Both extracts showed the presence of polyphenols, flavonoids, alkaloids and tannins compounds. These extracts exhibited potent antioxidant activity and showed an attenuation of severe convulsive seizures, a significant decrease in the frequency and duration of seizures and prolonged the latency of the onset seizure (p