Hepatitis E Vaccines Updates.

The development of a hepatitis E vaccine is imperative given its prevalence and the heightened risk it poses to specific populations. Hepatitis E virus infection, though often self-limiting, poses a significant threat to pregnant individuals and immunocompromised populations. This review delves into the historical trajectory of hepatitis E vaccine development and explores its potential impact on at-risk populations. Historically, efforts to formulate an effective vaccine against hepatitis E have been underway to mitigate the severity of the disease, particularly in regions where the infection is commonplace. As a self-limiting disease, the necessity of a vaccine becomes more pronounced when considering vulnerable demographics. Pregnant individuals face heightened complications, with potential adverse outcomes for both mother and child. Similarly, immunocompromised individuals experience prolonged and severe manifestations of the infection, necessitating targeted preventive measures. This review aims to provide a comprehensive overview of the milestones in hepatitis E vaccine development. By examining the historical progression, we aim to underscore the critical need for a vaccine to safeguard not only the general population but also those at elevated risk. The elucidation of the vaccine's journey will contribute valuable insights into its potential benefits, aiding in the formulation of informed public health strategies to combat hepatitis E effectively.

A case of giant labia majora lipoma in an adult.

Lipomas are common benign adipose tissue tumors but are infrequently found in the labia majora, especially at a large size. We report a case of a giant lipoma of the labia majora in a 37-year-old woman diagnosed by imaging methods and successfully treated by surgery. This case highlights the importance of considering lipoma in the differential diagnosis of labial masses and underscores the role of imaging in diagnosis. They need to be differentiated from liposarcoma or omental herniation into Nuck's canal. It also demonstrates the effectiveness of surgical management for large lipomas in sensitive areas, with attention to both medical and aesthetic outcomes.

Intrauterine device (IUD) embedded in bladder wall with calculus formation treated with cystoscopy: a case report.

In the realm of unusual gynecological complications, the displacement of an intrauterine device (IUD) into the bladder, resulting in stone formation, stands out as an exceptionally rare and perplexing condition. Such occurrences challenge diagnostic and therapeutic protocols, often leading to unique case studies that expand our understanding of IUD-related complications. We present an interesting case of a 50-year-old woman with a stone-forming ectopic IUD in the bladder diagnosed with imaging modalities and treated with cystoscopy, with a subsequent resolution of symptoms. This case underscores the importance of considering ectopic IUD placement in the differential diagnosis of patients presenting with urinary symptoms and a history of IUD use. Moreover, it emphasizes the role of imaging in the accurate diagnosis of such cases and highlights cystoscopy as an effective treatment modality for the removal of IUD and stones.

In vivo CRISPR/Cas9-mediated screen reveals a critical function of TFDP1 and E2F4 transcription factors in hematopoiesis.

Hematopoiesis is a continuous process of blood cell production driven by hematopoietic stem and progenitor cells (HSPCs) in the bone marrow. Proliferation and differentiation of HSPCs are regulated by complex transcriptional networks. In order to identify transcription factors with key roles in HSPC-mediated hematopoietic reconstitution, we developed an efficient and robust CRISPR/Cas9-based in vivo genetic screen. Using this experimental system, we identified the TFDP1 transcription factor to be essential for HSPC proliferation and post-transplant hematopoiesis. We further discovered that E2F4, an E2F transcription factor, serves as a binding partner of TFDP1 and is required for HSPC proliferation. Deletion of TFDP1 caused downregulation of genes associated with the cell cycle, with around 50% of these genes being identified as direct targets of TFDP1 and E2F4. Thus, our study expands the transcriptional network governing hematopoietic development through an in vivo CRISPR/Cas9-based genetic screen and identifies TFDP1/E2F4 as positive regulators of cell cycle genes in HSPCs.

Direct-Acting Antiviral Agents in Prevention of Maternal-Fetal Transmission of Hepatitis C Virus in Pregnancy.

Prior to the Food and Drug Administration approval of ledipaspavir/sofosbuvir (Harvoni®) in 2014, the treatment of hepatitis C was interferon plus or minus ribavirin. This treatment had low cure rates for hepatitis C virus and was teratogenic and therefore avoided in pregnant patients. Vertical transmission is the most common transmission of hepatitis C in pediatric patients, whereas medical equipment that was not properly cleaned and sterilized, blood products which were not checked (historically), sharing and reusing syringes and needles, and dialysis are the most common forms of hepatitis C transmission in adults. The treatment of pregnant women with direct-acting antivirals is important because the treatment of pediatric patients cannot begin until three years of age and does not always occur prior to the symptom development of hepatitis C. This review article will include glecaprevir/pibrentasvir (Mayvret®), sofosbuvir/velpatasvir (Epclusa®), and sofosbuvir/velpatasvir plus voxilaprevir (Vosevi®). We aim to review the teratogenic risk of direct-acting antivirals as well as currently published clinical trials and ongoing research on direct-acting antiviral hepatitis C treatment in pregnancy in this publication.

Subcutaneous Panniculitis-Like T-Cell Lymphoma With Hemophagocytic Lymphohistiocytosis.

Subcutaneous panniculitis-like T-cell lymphoma (SPTLP), a unique variant of primary cutaneous T-cell lymphomas, clinically mimics subcutaneous panniculitis. It is typified by the development of multiple plaques or subcutaneous erythematous nodules, predominantly on the extremities and trunk. Epidemiological findings reveal a greater incidence in females than males, affecting a wide demographic, including pediatric and adult cohorts, with a median onset age of around 30 years. Diagnosis of SPTLP is complex, hinging on skin biopsy analyses and the identification of T-cell lineage-specific immunohistochemical markers. Treatment modalities for SPTLP are varied; while corticosteroids may be beneficial initially for many patients, a substantial number require chemotherapy, especially in cases of poor response or relapse. Generally, SPTLP progresses slowly, yet approximately 20% of cases advance to hemophagocytic lymphohistiocytosis (HLH), often correlating with a negative prognosis. We report a case of a young male patient presenting with prolonged fever, multiple skin lesions accompanied by HLH, a poor clinical course, and eventual death, diagnosed postmortem with SPTLP. In addition, we also present a literature review of the current evidence of some updates related to SPTLP.

Appendiceal Diverticulitis Mimics Cecal Diverticulitis Diagnosed Preoperatively.

Appendiceal diverticulitis is an uncommon condition that clinically resembles acute appendicitis. However, it is an incidental finding in histopathological studies and is rarely diagnosed preoperatively by imaging studies. In this article, we present the clinical and imaging findings of a male patient presenting with right upper quadrant pain with a preoperative imaging diagnosis of appendiceal diverticulitis. He underwent laparoscopic appendectomy and confirmed the diagnosis of appendiceal diverticulitis. This is a rare preoperative diagnosis. The management is often like typical appendicitis which is appendectomy. It is important to differentiate it from diverticulitis of the small intestine or colon because these diseases usually require only conservative treatment.

Precise CRISPR-Cas9 gene repair in autologous memory T cells to treat familial hemophagocytic lymphohistiocytosis.

Familial hemophagocytic lymphohistiocytosis (FHL) is an inherited, often fatal immune deficiency characterized by severe systemic hyperinflammation. Although allogeneic bone marrow transplantation can be curative, more effective therapies are urgently needed. FHL is caused by inactivating mutations in proteins that regulate cellular immunity. Here, we used an adeno-associated virus-based CRISPR-Cas9 system with an inhibitor of nonhomologous end joining to repair such mutations in potentially long-lived T cells ex vivo. Repaired CD8 memory T cells efficiently cured lethal hyperinflammation in a mouse model of Epstein-Barr virus-triggered FHL2, a subtype caused by perforin-1 (Prf1) deficiency. Furthermore, repair of PRF1 and Munc13-4 (UNC13D)-whose deficiency causes the FHL subtype FHL3-in mutant memory T cells from two critically ill patients with FHL restored T cell cytotoxicity. These results provide a starting point for the treatment of genetic T cell immune dysregulation syndromes with repaired autologous T cells.

The evolutionary phylodynamics of human parechovirus A type 3 reveal multiple recombination events in South Korea.

Human parechovirus A (HPeV-A) is a causative agent of respiratory and gastrointestinal illnesses, acute flaccid paralysis encephalitis, meningitis, and neonatal sepsis. To clarify the characteristics of HPeV-A infection in children, 391 fecal specimens were collected from January 2014 to October 2015 from patients with acute gastroenteritis in Seoul, South Korea. Of these, 221/391 (56.5%) HPeV-A positive samples were found in children less than 2 years old. Three HPeV-A genotypes HPeV-A1 (117/221; 52.94%), HPeV-A3 (100/221; 45.25%), and HPeV-A6 (4/221; 1.81%) were detected, among which HPeV-A3 was predominant with the highest recorded value of 58.6% in 2015. Moreover, recombination events in the Korean HPeV-A3 strains were detected. Phylogenetic analysis revealed that the capsid-encoding regions and noncapsid gene 2A of the four Korean HPeV-A3 strains are closely related to the HPeV-A3 strains isolated in Canada in 2007 (Can82853-01), Japan in 2008 (A308/99), and Taiwan in 2011 (TW-03067-2011) while noncapsid genes P2 (2B-2C) and P3 (3A-3D) are closely related to those of HPeV-A1 strains BNI-788St (Germany in 2008) and TW-71594-2010 (Taiwan in 2010). This first report on the whole-genome analysis of HPeV-A3 in Korea provides insight into the evolving status and pathogenesis of HPeVs in children.

Effect of talc and vitamin E TPGS on manufacturability, stability and release properties of trilaurin-based formulations for hot-melt coating.

This study was focused on one particular case of hot-melt coating with trilaurin - a solid medium-chain monoacid triglyceride. The challenge of using trilaurin as coating agent in melting-based processes is linked to its relatively low melting profile: 15.6 °C (Tm,α), 35.1 °C ( [Formula: see text] ) and 45.7 °C (Tm,ß). From a process perspective, the only possibility to generate products coated with formulations composed of trilaurin is by setting thermal operational conditions above Tm,α. From a material perspective, this processing possibility depends principally on trilaurin crystallisation which was investigated via a set of analytical techniques including turbidimetry, calorimetry, hot-melt goniometry, and polarised light microscopy. A highly soluble drug model substrate (sodium chloride crystals) was coated with three selected trilaurin-based formulations: (i) trilaurin, (ii) trilaurin plus talc, and (iii) trilaurin plus vitamin E TPGS and talc. Coated salt crystals were then analysed to investigate processing performance, coating quality, stability and release properties under digestion effect. The results show that firstly, talc addition promotes nucleation and crystal growth and, as a consequence, it facilitates the manufacture of trilaurin-based formulations. Secondly, the formulation of a solid triglyceride and a hydrophilic surfactant could potentially cause release instability, but formula (iii) was found to be stabilised by a mechanism whereby trilaurin crystallization enhanced in the presence of talc immobilised vitamin E TPGS in its crystal lattice. Thirdly, talc addition did not significantly influence trilaurin digestion which endows products with an immediate release in lipolytic conditions instead of an extended liberation in pure water. Nor did the addition of one or two additives alter the extent of trilaurin digestion under the conditions studied. These important findings relate to product manufacturability, stability, and release properties. A good understanding of material properties (e.g. crystallisation, polymorphism, digestibility) is essential for melt-processing, lipid coating stabilising and modulation of release profile of solid lipid-coated product, as demonstrated in this case study with trilaurin.

A Review of Classification, Diagnosis, and Management of Hydrocele.

This article summarizes and updates a number of issues related to hydrocele including anatomy, embryology, classification, etiology, clinical manifestations, imaging findings, and management. Hydrocele is an abnormal collection of serous fluid between the parietal and visceral layers arising from the mesothelial lining of the tunica vaginalis that surrounds the testis and spermatic cord directly. Hydroceles result from an imbalance of secretion and reabsorption of fluid from the tunica vaginalis. Hydroceles can be divided into two types as primary and secondary. The diagnosis should be based on medical history, clinical manifestations, and imaging studies. Understanding the causes and types of hydroceles is useful for accurately diagnosing and treatment strategy. Hydroceles can be managed by conservative treatment, fluid aspiration, or hydrocelectomy.

Primary Hepatic Schwannoma: Case Report and Literature Review.

Primary hepatic schwannoma is an extremely rare tumor with a good prognosis. Preoperative diagnosis is often challenging due to nonspecific clinical symptoms and its rarity. Here, we report a case of a 56-year-old male patient misdiagnosed with malignant liver tumor, later identified as primary hepatic schwannoma. Furthermore, clinical and histopathological features of 19 cases of primary hepatic schwannoma are also documented. The age of the patients ranged from 38 to 72 years, with a mean age of 56.4 years, and the disease was more common in females. Patients typically presented without clinical symptoms and were not associated with neurofibromatosis type 1. Histopathological features of the tumor were similar to soft tissue schwannoma, characterized by a thick capsule consisting of Antoni A and Antoni B areas. Immunohistochemically, the tumor showed strong positivity and diffusely stained with S-100, while being negative for CD34, CD117, and SMA. Complete resection of the tumor was achieved in all patients. The prognosis was favorable, with no signs of recurrence. Follow-up examinations revealed disease-free survival ranging from 6 to 27 months. Differential diagnosis of primary hepatic schwannoma from malignant liver tumors and metastatic liver tumors can be made based on histopathological features and immunohistochemical staining with S-100.

Comparison of two treatments for atlantoaxial instability injury: C1-C2 transarticular screw fixation versus C1 lateral mass-C2 pedicle screw fixation.

Objective: This study evaluated the effectiveness and safety of C1-C2 transarticular screw fixation (transarticular screw fixation com-bined with bone grafting) and C1 lateral mass-C2 pedicle screw fixation (modified Harms technique) in patients with C1-C2 instability. Materials and methods: This prospective, self-controlled, single-center study evaluated two fixation techniques for the treatment of atlantoaxial instability injury. From June 2006 to February 2017, 118 patients were admitted to our hospital because of atlantoaxial instability injury. These patients were divided into two groups: group 1, including 52 patients who underwent C1-C2 transarticular screw fixation (C1C2-TAS group), and group 2, including 66 patients who underwent C1 lateral mass-C2 pedicle screw fixation (C1LM-C2PS group). Results: There were significant differences in the operation time, blood loss amount, and hospital stay length between the groups (p<0.001). The mean operation time (78.94 vs. 110.91 min; p=0.0003) and hospital stay length (5.31 vs. 8.34 days; p=0.0003) were shorter, and the mean blood loss amount during surgery (122.31 vs. 258.33 mL; p<0.0001) was smaller in the C1C2-TAS group than in the C1LM-C2PS group. The surgical complication rate was low and no vertebral artery injury was observed. After surgery, the clinical presentations were significantly reduced in both groups. The patients showed sati-sfactory internal fixation on postoperative radiography and computed tomography. Conclusion: Both C1-C2 transarticular screw fixation and C1 lateral mass-C2 pedicle screw fixation are effective and safe in treat-ing atlantoaxial instability injury. Notably, C1-C2 transarticular screw fixation yields a shorter operation time and hospital stay length and a smaller intraoperative blood loss amount than does C1 lateral mass-C2 pedicle screw fixation.

Corrigendum to "Novel approach for infrared spectroscopic quantitation of azithromycin in commercial tablets employing paracetamol as matrix modifier" [Heliyon 9 (3) (March 2023) Article e14647].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e14647.].

Chemical composition, anti-inflammatory and cytotoxic activity of essential oils from two Luvunga species (L. scandens and L. hongiaoensis) from Vietnam.

New essential oils (EOs) extracted from different parts of two Luvunga species (L. scandens and L. hongiaoensis) from Vietnam were investigated for their chemical composition, anti-inflammatory and cytotoxic activity. Sixty-nine total compounds were identified in the EOs by GC/MS. The major constituent of the leaf, fruit, and root EOs from L. scandens was ß-caryophyllene (71.5%, 63.0%, and 31.5% respectively). The main compounds in L. hongiaoensis EOs were ß-elemene (34.3% in leaf oil) and caryophyllene oxide (21.2% in root oil, 19.4% in stem oil). The EO from L. scandens fruits significantly inhibited nitric oxide production on LPS-induced RAW264.7 cells (IC50 = 37.95 ± 2.76 µg/mL). The EOs from L. hongiaoensis roots and L. scandens leaves and fruits exhibited cytotoxic activity against MCF-7, SK-LU-1, and HepG2 (IC50 from 49.74 ± 3.36 to 97.82 ± 8.61 µg/mL). This is the first report on L. hongiaoensis EOs and significantly complements the composition and bioactivity of L. scandens EOs.

Application of a Spacer-nick Gene-targeting Approach to Repair Disease-causing Mutations with Increased Safety.

The CRISPR/Cas9 system is a powerful tool for gene repair that holds great potential for gene therapy to cure monogenic diseases. Despite intensive improvement, the safety of this system remains a major clinical concern. In contrast to Cas9 nuclease, Cas9 nickases with a pair of short-distance (38-68 bp) PAM-out single-guide RNAs (sgRNAs) preserve gene repair efficiency while strongly reducing off-target effects. However, this approach still leads to efficient unwanted on-target mutations that may cause tumorigenesis or abnormal hematopoiesis. We establish a precise and safe spacer-nick gene repair approach that combines Cas9D10A nickase with a pair of PAM-out sgRNAs at a distance of 200-350 bp. In combination with adeno-associated virus (AAV) serotype 6 donor templates, this approach leads to efficient gene repair with minimal unintended on- and off-target mutations in human hematopoietic stem and progenitor cells (HSPCs). Here, we provide detailed protocols to use the spacer-nick approach for gene repair and to assess the safety of this system in human HSPCs. The spacer-nick approach enables efficient gene correction for repair of disease-causing mutations with increased safety and suitability for gene therapy. Graphical overview.

Traumatic rupture of congenital cystic adenomatoid malformation mimicking traumatic pulmonary pseudocyst: a case report.

Thoracic trauma is commonly encountered in daily clinical practice; however, blunt thoracic trauma in patients with congenital cystic adenomatoid malformation (CCAM) is rare. CCAM rupture denotes a broad spectrum of manifestations on imaging and may be misdiagnosed as many other conditions. Consequently, this leads to inaccurate treatment and poor patient outcomes. We report the case of a girl with the initial diagnosis of a cavitary lung lesion that was likely a traumatic pulmonary pseudocyst or CCAM. The patient received medical therapy for 20 days; however, her condition did not improve. Subsequently, she underwent right lower lobectomy. Ruptured CCAM was confirmed during surgery and with histopathology. No complications occurred postoperatively, and the patient made a good recovery.

Novel approach for infrared spectroscopic quantitation of azithromycin in commercial tablets employing paracetamol as matrix modifier.

The ATR-FTIR quantitation of azithromycin in three products of commercial tablets was carried out on product specific quantitative regression models using powdered paracetamol as matrix modifier to overcome the variation of spectral response and influence of sample matrix. For each product, a PLS quantitative regression model was established using training infrared spectra obtained from reference mixtures (reference powders with known mass content (%, w/w) of azithromycin mixed homogenously with paracetamol to have mass percentage of azithromycin over total mass of azithromycin and paracetamol (PA) from 30% to 70%). The spectral data were collected in wavenumber range depending on commercial product within the wavenumber zone from 1300 cm-1 to 1750 cm-1 to build quantitative regression models. To quantify azithromycin in any commercial batch of the same product, the homogenized sample powder was mixed with paracetamol to have mixtures with PA value about 50% to record infrared spectrum. The actual amount of azithromycin would then be calculated from spectral response of unknown sample and the pre-established quantitative regression model. Each quantitative regression model was validated according to the current requirements of ICH guideline Q2R1 and those of AOAC International in term of specificity, accuracy, precision, long-term robustness and reliability. The validation results proved that the quantitative regression models were accurate, precise, reliable and robust, able to provide quantitative results of azithromycin in tablets equivalent to those provided by official HPLC method of USP44.