Non-native Pathway Engineering with CRISPRi for Carbon Dioxide Assimilation and Valued 5-Aminolevulinic Acid Synthesis in Escherichia coli Nissle.

Carbon dioxide emission and acidification during chemical biosynthesis are critical challenges toward microbial cell factories' sustainability and efficiency. Due to its acidophilic traits among workhorse lineages, the probiotic Escherichia coli Nissle (EcN) has emerged as a promising chemical bioproducer. However, EcN lacks a CO2-fixing system. Herein, EcN was equipped with a simultaneous CO2 fixation system and subsequently utilized to produce low-emission 5-aminolevulinic acid (5-ALA). Two different artificial CO2-assimilating pathways were reconstructed: the novel ribose-1,5-bisphosphate (R15P) route and the conventional ribulose-5-phosphate (Ru5P) route. CRISPRi was employed to target the pfkAB and zwf genes in order to redirect the carbon flux. As expected, the CRISPRi design successfully strengthened the CO2 fixation. The CO2-fixing route via R15P resulted in high biomass, while the engineered Ru5P route acquired the highest 5-ALA and suppressed the CO2 release by 77%. CO2 fixation during 5-ALA production in EcN was successfully synchronized through fine-tuning the non-native pathways with CRISPRi.

3D evaluation of sagittal inclination of the maxillary dentition in relation to facial landmarks: A cohort study.

BACKGROUND: The determination of the maxillary occlusal plane presents a significant clinical challenge in the treatment of edentulous patients as well as it is critical for complex full-mouth reconstructions in dentate patients, including those with implant-supported rehabilitations. While the use of a Fox plane plate is standard in edentulous cases, its application in dentate patients lacks thorough documentation in existing literature. PURPOSE: This clinical study assessed the sagittal position of the maxillary dentition in relation to facial landmarks using a digital three-dimensional analysis and evaluated the suitability and reliability of applying a simulated Fox plane plate, also known as an occlusal plane guide, in dentate patients. MATERIALS AND METHODS: Eighty-one subjects were recruited at the Department of Prosthetic Dentistry of Goethe University Frankfurt, Germany, according to specific inclusion criteria. Intraoral and facial scans were obtained and analyzed using GOM Inspect Pro software (GOM, Braunschweig, Germany). The angles between the maxillary occlusal plane and three variations each of Camper's plane and ala-tragus line, relating to superior, middle, and inferior tragus points, were measured. These modified planes were then compared to a plane established by a simulated digital Fox plane plate, which was adapted to the maxillary anterior teeth and the lowest point of the posterior teeth in both quadrants. RESULTS: A total of 81 subjects (58 female and 23 male) with a mean age of 23.9 years were evaluated in this study. No significant angular difference was found between the angles of the maxillary occlusal plane compared with superior Camper's plane, middle Camper's plane, or superior ala-tragus line (p >0.05). The smallest angle occurred between superior Camper's plane and the maxillary occlusal plane on both the right (3.443°) and left (3.535°) sides. The application of a Fox plane plate resulted in two different occlusal planes in 70% of patients, significantly deviating from the digitally determined plane (p <0.05). CONCLUSION: Superior and middle Camper's planes, along with superior ala-tragus line, can be considered approximately parallel reference planes and are suitable for routine determining of the maxillary occlusal plane in restorative treatments. However, in contrast to digital evaluation methods, the application of a Fox plane plate in dentate patients showed high variability, indicating its low reproducibility due to its ambiguous positioning on the maxillary dentition. Clinical trial registration site: https://drks.de/search/de/trial/DRKS00030166.

Exoscopic versus Microscopic Surgery in 5-ALA-Guided Resection of High-Grade Gliomas.

Background: Glioma surgery has been remarkably enhanced in the past 2 decades, with improved safety and limited but improved life expectations. The fluorescence-guided resection of high-grade gliomas (HGGs) plays a central role in this sense, allowing a greater extent of resection (EOR). The introduction of exoscopic-guided surgery may be considered in implementing fluorescence techniques over traditional microscopes. We present the application and the advantages of exoscopic-guided surgery compared to microscopic surgery in tumor resection guided by 5-ALA fluorescence in patients with HGGs. Methods: Ten consecutive patients underwent surgery for HGG resection. The surgery was performed via an exoscopic-guided procedure (Olympus ORBEYE) and after the oral administration of Gliolan 5 h before the procedure. During surgery, the procedure shifted to using a microscopic (Kinevo 900, Zeiss) view. The intensity of the fluorescence under the two different procedures was subjectively measured in different picture samples during the surgery on a 1 to 5 (from minimum to maximum) scale. The brightness of the surgical field and the detailing of the anatomy were also analyzed comparatively. Results: Among the ten patients, the histopathological diagnosis was an high-grade glioma in all cases. In nine cases, it was possible to achieve gross total resection. There was no perioperative mortality. The median fluorescence intensity, on a scale of 1-5, was 4.5 in the exoscope group and 3.5 in the microscope group (p < 0.01). Conclusions: The exoscopic-guided surgery adds advantages to traditional fluorescence-guided surgery with 5-aminolevulinic acid. Beyond the important advantage of low cost and the possibility to perform collaborative surgeries, it adds a plain and continuous visualization of the tumor and offers advantages in the surgical field of fluorescence-guided glioma surgery compared to the microscopic-guided one.

Application of Photodynamic Therapy with 5-Aminolevulinic Acid to Extracorporeal Photopheresis in the Treatment of Cutaneous T-Cell Lymphoma: A First-in-Human Phase I/II Study.

Extracorporeal photopheresis (ECP) is a therapeutic modality used for T-cell-mediated disorders. This approach involves exposing isolated white blood cells to photoactivatable 8-methoxypsoralen (8-MOP) and UVA light, aiming to induce apoptosis in T-cells and thereby modulate immune responses. However, conventional 8-MOP-ECP lacks cell selectivity, killing both healthy and diseased cells, and has shown limited treatment efficacy. An alternative approach under investigation involves the use of 5-aminolevulinic acid (ALA) in conjunction with light, referred to as ALA-based photodynamic therapy. Our previous ex vivo studies suggest that ALA-ECP exhibits greater selectivity and efficiency in killing T-cells derived from patients with T-cell-mediated disorders compared to those treated with 8-MOP-ECP. We have conducted a clinical phase I-(II) study evaluating ALA-ECP safety and tolerability in cutaneous T-cell lymphoma (CTCL). Here, 20 ALA-ECP treatments were administered to one CTCL patient, revealing no significant changes in vital signs. Two adverse events were reported; both evaluated by the Internal Safety Review Committee as non-serious. In addition, five conceivable events with mainly mild symptoms took place. During the study period, a 53% reduction in skin involvement and a 50% reduction in pruritus was observed. In conclusion, the results indicate that ALA-ECP treatment is safe and well tolerated.

Does 5-ALA Fluorescence Microscopy Improve Complete Resectability in Cerebral/Cerebellar Metastatic Surgery? A Retrospective Data Analysis from a Cranial Center.

(1) Background: In this study, the intraoperative fluorescence behavior of brain metastases after the administration of 5-aminolevulinic acid (5-ALA) was analyzed. The aim was to investigate whether the resection of brain metastases using 5-ALA fluorescence also leads to a more complete resections and thus to a prolongation of survival; (2) Methods: The following variables have been considered: age, sex, number of metastases, localization, involvement of eloquent area, correlation between fluorescence and primary tumor/subtype, resection, and survival time. The influence on the degree of resection was determined with a control MRI within the first three postoperative days; (3) Results: Brain metastases fluoresced in 57.5% of cases. The highest fluorescence rates of 73.3% were found in breast carcinoma metastases and the histologic subtype adenocarcinoma (68.1%). No correlation between fluorescence behavior and localization, primary tumor, or histological subtype was found. Complete resection was detected in 82.5%, of which 56.1% were fluorescence positive. There was a trend towards improved resectability (increase of 12.1%) and a significantly longer survival time (p = 0.009) in the fluorescence-positive group; (4) Conclusions: 5-ALA-assisted extirpation leads to a more complete resection and longer survival and can therefore represent a low-risk addition to modern surgery for brain metastases.

Safety and Efficacy of Laser Interstitial Thermal Therapy as Upfront Therapy in Primary Glioblastoma and IDH-Mutant Astrocytoma: A Meta-Analysis.

Although primary studies have reported the safety and efficacy of LITT as a primary treatment in glioma, they are limited by sample sizes and institutional variation in stereotactic parameters such as temperature and laser power. The current literature has yet to provide pooled statistics on outcomes solely for primary brain tumors according to the 2021 WHO Classification of Tumors of the Central Nervous System (WHO CNS5). In the present study, we identify recent articles on primary CNS neoplasms treated with LITT without prior intervention, focusing on relationships with molecular profile, PFS, and OS. This meta-analysis includes the extraction of data from primary sources across four databases using the Covidence systematic review manager. The pooled data suggest LITT may be a safe primary management option with tumor ablation rates of 94.8% and 84.6% in IDH-wildtype glioblastoma multiforme (GBM) and IDH-mutant astrocytoma, respectively. For IDH-wildtype GBM, the pooled PFS and OS were 5.0 and 9.0 months, respectively. Similar to rates reported in the prior literature, the neurologic and non-neurologic complication rates for IDH-wildtype GBM were 10.3% and 4.8%, respectively. The neurologic and non-neurologic complication rates were somewhat higher in the IDH-mutant astrocytoma cohort at 33% and 8.3%, likely due to a smaller cohort size.

Case Report: MYH9-related disease caused by Ala44Pro mutation in a child with a previous diagnosis of chronic immune thrombocytopenia.

MYH9-related disease, a rare autosomal dominant platelet disorder characterized by thrombocytopenia, giant platelets, and leukocyte inclusion bodies, may mimic immune thrombocytopenia in children unless suspected and carefully excluded. Here, we present a case involving a three-year-old girl with mild bleeding symptoms since infancy, previously diagnosed with chronic immune thrombocytopenia. The patient exhibited isolated thrombocytopenia and lacked any family history of thrombocytopenia, hearing impairment, or renal failure. Examination of peripheral blood smears via light microscopy revealed significant platelet macrocytosis with giant platelets and basophilic Döhle-like bodies in the neutrophils. Subsequent sequencing analysis of MYH9 gene identified a p.Ala44Pro mutation. Throughout a six-year follow-up period, the patient's condition remained stable. Our report underscores the significance of identifying leukocyte inclusion bodies in peripheral blood smears and considering MYH9-related diseases, even in instances of chronic macrothrombocytopenia devoid of familial history or non-hematological manifestations.

The Effect of NF-κB Deactivation on Cancer Cell Response to ALA Mediated Photodynamic Therapy.

OBJECTIVE: Breast cancer is one of the most widespread tumors among women worldwide, which is difficult to treat due to the presence of chemoresistance and the risk of tumor recurrence and metastasis. There is a pressing necessity to develop efficient treatments to improve response for treatment and increase prolong survival of breast cancer patients. Photodynamic therapy (PDT) has attracted interest for its features as a noninvasive and relatively selective cancer treatment. This method relies on light-activated photosensitizers that, upon absorbing light, generate reactive oxygen species (ROS) with powerful cell-killing outcomes. Nuclear factor kappa B (NF-κB), a transcription factor, plays a key role in cancer development by regulating cell proliferation, differentiation, and survival. Inhibiting NF-κB can sensitize tumor cells to chemotherapeutic agents. Dimethyl fumarate (DMF), an NF-κB inhibitor approved by the FDA for multiple sclerosis treatment, has further shown promise in suppressing breast cancer cell growth in vitro. We hypothesized that combining PDT with Dimethyl fumarate (DMF) could further enhance therapeutic efficacy for both treatment modalities. METHODS: In the current study, we explored the PDT effect of 1 and 2 mM aminolaevulinic acid (ALA) and low-power He-Ne laser irradiation combined with different concentrations of DMF (2.5, 1.25, or 0.652 µg/ml) against hormone nonresponsive AMJ13 breast cancer cell line that is derived from Iraqi patient. RESULTS: Our results demonstrated that co-administration with all tested DMF concentrations significantly enhanced the cytotoxicity of PDT antitumor effect. The combination index analysis showed presence of synergism in combining PDT with DMF. CONCLUSION: This finding suggests that the combination of PDT with DMF could be a promising novel strategy against triple negative breast cancer that could be applied clinically due to the fact that both of these treatments are already clinically approved therapies.

An innovative approach to detect circulating tumor cells.

In cancer research, circulating tumor cells (CTCs) were identified as the main drivers of metastasis. They are vital for early detection and prevention of metastasis during cancer treatment. Even though continuous progress in research offers more and more tools to combat cancer, we still lack a proper arsenal of therapeutics. Especially in tumors with close to no targeting options, like triple-negative breast cancer, early detection is often the main difference between successful and failed therapy. When such tumors are detected too late, they may have already produced plenty of CTCs, likely causing metastasis, which is the primary reason for tumor-associated deaths. Detecting those CTCs early on could substantially impact therapy outcomes and the 5-year survival rate. In our study, we developed and evaluated a reliable and affordable CTC screening method based on flow cytometry and 5-aminolevulinic acid (5-ALA) staining. We successfully established a circulation model for 5-ALA and CTCs research and demonstrated that the method can detect an average of 11 ±â€¯3.3 CTCs out of 10,000 peripheral blood mononuclear cells, representing as low as approximately 0.1 % with a reasonable number of false positive events. Additionally, we present initial results on a theranostic approach using 5-ALA converted to protoporphyrin IX. The outcomes of this study might contribute significantly to the further development of CTC detection and the overall detection and treatment of cancer.

Ki67 Index Correlates with Tumoral Volumetry and 5-ALA Residual Fluorescence in Glioblastoma.

BACKGROUND: Malignant gliomas are the most prevalent primary malignant cerebral tumors. Preoperative imaging plays an important role, and the prognosis is closely related to surgical resection and histomolecular aspects. Our goal was to correlate Ki67 indexes with tumoral volumetry in semiautomatic segmentation on preoperative magnetic resonance images and residual fluorescence in a 5-ALA-assisted resection cohort. METHODS: We included 86 IDH-wildtype glioblastoma patients with complete preoperative imaging submitted to 5-ALA assisted resections. Clinical, surgical, and histomolecular findings were also obtained. Preoperative magnetic resonance studies were preprocessed and segmented semiautomatically on Visualization and Analysis for whole tumor (WT) on 3D FLAIR, enhancing tumor (ET), and necrotic core on 3D postgadolinium T1. We performed a linear regression analysis for Ki67 and a multivariate analysis for surgical outcomes. RESULTS: Higher Ki-67 indexes correlated positively with higher WT (P = 0.048) and ET (P = 0.002). Lower Ki67 correlated with 5-ALA free margins (P = 0.045). WT and ET volumes correlated with the extent of resection (EOR; P = 0.002 and 0.002, respectively). Eloquence did not impact EOR (P = 0.14). CONCLUSIONS: There is a correlation between Ki67, the metabolically active tumoral volumes (WT and ET), and 5-ALA residual fluorescence. Methodological inconsistencies are probably responsible for contradictory literature findings, and further prospective studies are needed to validate and reproduce these findings.

The Thr92Ala polymorphism in the type 2 deiodinase gene is linked to depression in patients with COVID-19 after hospital discharge.

Background: The Thr92Ala-DIO2 polymorphism has been associated with clinical outcomes in hospitalized patients with COVID-19 and neuropsychiatric diseases. This study examines the impact of the Thr92Ala-DIO2 polymorphism on neuropsychological symptoms, particularly depressive symptoms, in patients who have had moderate to severe SARS-CoV-2 infection and were later discharged. Methods: Our prospective cohort study, conducted from June to August 2020, collected data from 273 patients hospitalized with COVID-19. This included thyroid function tests, inflammatory markers, hematologic indices, and genotyping of the Thr92Ala-DIO2 polymorphism. Post-discharge, we followed up with 68 patients over 30 to 45 days, dividing them into depressive (29 patients) and non-depressive (39 patients) groups based on their Beck Depression Inventory scores. Results: We categorized 68 patients into three groups based on their genotypes: Thr/Thr (22 patients), Thr/Ala (41 patients), and Ala/Ala (5 patients). Depressive symptoms were less frequent in the Thr/Ala group (29.3%) compared to the Thr/Thr (59.1%) and Ala/Ala (60%) groups (p = 0.048). The Thr/Ala heterozygous genotype correlated with a lower risk of post-COVID-19 depression, as shown by univariate and multivariate logistic regression analyses. These analyses, adjusted for various factors, indicated a 70% to 81% reduction in risk. Conclusion: Our findings appear to be the first to show that heterozygosity for Thr92Ala-DIO2 in patients with COVID-19 may protect against post-COVID-19 depression symptoms up to 2 months after the illness.

Effects of Photodynamic Therapy Using 5 -Aminolevulinic Acid (ALA) Loaded Acrylic Nanoparticles (ANPs) on HaCaT Cells.

Objective: ALA-PDT (5-aminolevulinic acid photodynamic therapy) is a central modality in the treatment of skin diseases. Increasing the bioavailability of ALA remains a critical issue. With this in mind, our study explores a novel route of ALA delivery by loading acrylic nanoparticles (ANPs). Methods: ALA-ANPs were synthesized by emulsion polymerisation and characterised by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). The effects of ALA-ANPs on HaCaT cell line were evaluated, including characteristics, morphological changes, protoporphyrin IX (PpIX) fluorescence kinetics, reactive oxygen species (ROS) levels, mitochondrial membrane potential and ki67 expression in these cells. Results: The ANPs had uniform sizes, smooth surfaces and excellent light transmittance, with diameters of 150-200 nm. In contrast, the ALA - ANPs had uneven surfaces and poor light transmittance, with diameters of 220-250 nm. During 12 hours of co-incubation of HaCaT cells with ALA, the intracellular accumulation of PpIX increased over time. Notably, after 6 hours of incubation, PpIX levels induced by 1.81 mg/mL ALA-ANPs exceeded those induced by 1.0 mM ALA (p < 0.01). CCK-8 results showed a positive correlation between PDT-induced inhibition of HaCaT cell proliferation and ALA concentration when ALA concentration remained below 2.0 mM. Compared to the 1.0 mM ALA group, the 1.81 mg/mL ALA-ANPs group showed decreased mitochondrial membrane potential, ki67 immunofluorescence intensity and cell proliferation. In contrast, ROS levels were significantly increased in the 1.81 mg/mL ALA-ANPs group (p < 0.01). Conclusion: Loading ANPs provide improved stability and potency for ALA. The ALA-ANPs-PDT approach has superior inhibitory effects on HaCaT proliferation in vitro.

Minimally Invasive Semiconductor Laser Surgery Combined with 5-ALA Photodynamic Therapy for a Chronic Hyperplastic Candidiasis Patient Who Is Ineffective to Antifungal Therapy.

Background: Chronic hyperplastic candidiasis (CHC) is a chronic oral mucosal infection caused by Candida, which has potential for malignant transformation. Diagnosing CHC can be challenging due to its various manifestations. In addition, fungal treatments often prove to be ineffective, highlighting the urgent need for a new safe and efficient treatment approach. Given the potential of CHC to transform into malignancy, it is crucial to emphasize dynamic monitoring and follow-up after treatment. Objective: We attempted to investigate the effect of semiconductor laser pretreatment combined with 5-amino-levulinic acid (5-ALA) photodynamic therapy (PDT) for CHC. Methods: We presented the successful treatment of CHC with mild dysplasia in a 30-year-old man using semiconductor laser and 5-ALA PDT after antifungal therapy proved ineffective. Toluidine blue staining, autofluorescence imaging, and DNA image cytometry were combined to dynamically monitor the progress of the disease. Results: We have obtained positive outcomes with the use of laser combined with PDT treatment. The patients experienced only mild adverse reactions after the treatment, and there was no indication of recurrence or malignant transformation during the subsequent follow-up period, as observed through various auxiliary examinations. Conclusions: This case report suggests that semiconductor laser surgery combined with PDT could be a promising treatment option for patients with CHC who do not respond to antifungal therapy. In addition, the use of combined noninvasive examinations might provide a more accurate assessment of malignant transformation in patients with CHC.

Effectiveness of 5-aminolevulinic acid photodynamic therapy in treating dissecting cellulitis of the scalp and pathological changes in skin lesions: A retrospective study.

BACKGROUND: Dissecting cellulitis of the scalp (DCS) has a significant impact on the physical well-being and body image of the patient. Since DCS often responds poorly to conventional treatments, there is a need to identify alternative treatment strategies. This study aimed to explore the effectiveness of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in treating DCS. METHODS: Twelve male patients with DCS treated solely with ALA-PDT between June 2022 and June 2023 at our institution were enrolled in this study. Two patients underwent a biopsy before and after treatment for comparison. The efficacy of the treatments was assessed 10 days after treatment by evaluating the symptom scores recorded on medical records and by assessing the photographs acquired before and after treatment. In addition, the impact of the treatment on pain relief and median recurrence rate were also extracted. RESULTS: Out of the 12 enrolled patients, the majority of the patients (75%) had a significant reduction in the nodules or abscesses. The pain relief was significant in 3 patients (25%), and moderate in 7 patients (58.3%). For the subcutaneous sinus tract symptoms, 3 patients (27.3%) showed moderate improvement, and 7 (63.6%) had a mild improvement. Six patients (75%) had mild improvement in their alopecia. The pathology results showed a decrease in the number of lymphocytes, macrophages, and neutrophils within the skin lesions following the administration of ALA-PDT. CONCLUSION: ALA-PDT can effectively reduce the DCS symptoms and the number of lymphocytes, macrophages, and neutrophils within the skin lesions.

Pharmaceutical equivalent 5-aminolevulinic acid fluorescence guided resection of central nervous system tumors: feasibility, safeness and cost-benefit considerations.

PURPOSE: 5-aminolevulinic acid (5-ALA) fluorescence-guided resection (FGR) has been an essential tool in the 'standard of care' of malignant gliomas. Over the last two decades, its indications have been extended to other neoplasms, such as metastases and meningiomas. However, its availability and cost-benefit still pose a challenge for widespread use. The present article reports a retrospective series of 707 cases of central nervous system (CNS) tumors submitted to FGR with pharmacological equivalent 5-ALA and discusses financial implications, feasibility and safeness. METHODS: From December 2015 to February 2024, a retrospective single institution series of 707 cases of 5-ALA FGR were analyzed. Age, gender, 5-ALA dosage, intraoperative fluorescence finding, diagnosis and adverse effects were recorded. Financial impact in the surgical treatment cost were also reported. RESULTS: there was an additional cost estimated in $300 dollars for each case, increasing from 2,37 to 3,28% of the total hospitalization cost. There were 19 (2,69%) cases of asymptomatic photosensitive reaction and 2 (0,28%) cases of photosensitive reaction requiring symptomatic treatment. 1 (0,14%) patient had a cutaneous rash sustained for up to 10 days. No other complications related to the method were evident. In 3 (0,42%) cases of patients with intracranial hypertension, there was vomiting after administration. CONCLUSION: FGR with pharmacological equivalent 5-ALA can be considered safe and efficient and incorporates a small increase in hospital expenses. It constitutes a reliable solution in avoiding prohibitive costs worldwide, especially in countries where commercial 5-ALA is unavailable.

Current Insights into the Effects of Dietary α-Linolenic Acid Focusing on Alterations of Polyunsaturated Fatty Acid Profiles in Metabolic Syndrome.

The plant-derived α-linolenic acid (ALA) is an essential n-3 acid highly susceptible to oxidation, present in oils of flaxseeds, walnuts, canola, perilla, soy, and chia. After ingestion, it can be incorporated in to body lipid pools (particularly triglycerides and phospholipid membranes), and then endogenously metabolized through desaturation, elongation, and peroxisome oxidation to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), with a very limited efficiency (particularly for DHA), beta-oxidized as an energy source, or directly metabolized to C18-oxilipins. At this moment, data in the literature about the effects of ALA supplementation on metabolic syndrome (MetS) in humans are inconsistent, indicating no effects or some positive effects on all MetS components (abdominal obesity, dyslipidemia, impaired insulin sensitivity and glucoregulation, blood pressure, and liver steatosis). The major effects of ALA on MetS seem to be through its conversion to more potent EPA and DHA, the impact on the n-3/n-6 ratio, and the consecutive effects on the formation of oxylipins and endocannabinoids, inflammation, insulin sensitivity, and insulin secretion, as well as adipocyte and hepatocytes function. It is important to distinguish the direct effects of ALA from the effects of EPA and DHA metabolites. This review summarizes the most recent findings on this topic and discusses the possible mechanisms.

Transient contribution of the sphenoid ala major to the socket of the temporomandibular joint in near-term fetuses.

The temporomandibular joint (TMJ) is a complex structure that plays a vital role in the movement of the jaw. Some anatomy and dental textbooks show that, at the medial margin, the TMJ capsule attaches to a suture between the sphenoid ala major and the temporal bone squamosa. In near-term fetuses, the ala major extends posterolaterally to approach the TMJ. In this study, we aimed to investigate the contribution of the sphenoid ala major to the socket of the TMJ in near-term fetuses. We examined histological sections from 22 human fetuses (approximately 15-40 weeks). At midterm, the lateral and superior walls of the TMJ cavity were formed by the temporal bone squamosa, whereas the ala major was distant from the joint. However, at near-term, the ala major formed the medial wall of almost the entire part of the joint cavity. The top of the TMJ was attached to both the squamosa and ala major, with the condylar head consistently separated from the sphenoid by the joint disk. We observed a significant descent of the middle cranial fossa in near-term fetuses, which brought the ala major close to the TMJ. This transient position of the TMJ near the sphenoid is likely due to brain enlargement and posterolateral growth of the ala major. After birth, occlusion causes the anterior growth of the mandibular fossa of the squamosa, which moves the ala major away from the TMJ. Similarly, the lateral growth of the sphenoid toward the squamosa suture may also stop in children.

Efficacy and Safety of 5-Aminolevulinic Acid Photodynamic Therapy for Treating Cervical and Vaginal Intraepithelial Neoplasia.

Persistent HPV infections may cause cervical and vaginal intraepithelial neoplasia (CIN and VaIN). Traditional methods might destroy the structure and function of the cervix. 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a non-invasive targeted therapy. This study aims to evaluate the efficacy and safety of ALA-PDT for CIN and VaIN and the clearance of HPV. A retrospective study of 303 patients who confirmed CIN or VaIN and received ALA-PDT was conducted. All the patients were followed up at six and twelve months after treatment and then annually thereafter. The effect was evaluated through HPV genotyping, a cytology test, and colposcopy-directed biopsy if necessary. After ALA-PDT, the remission rates for CIN 2, CIN 3, VaIN 2, and VaIN 3 were 90.6%, 88.5%, 87.3%, and 77.8%. For CIN 1, the remission rate at the six-month follow-up was 93.1%. The total HPV clearance rates were 72.5% at the six-month follow-up and 85.7% at the 12-month follow-up. The most common adverse event was vaginal discharge. No severe adverse effect was observed. ALA-PDT is an effective and safe treatment for all grades of CIN and VaIN and is helpful in clearing HPV with minimal side effects. This treatment may not influence fertility and delivery.

Comparative Study of 5-Aminolevulinic Acid-Mediated Photodynamic Therapy and the Loop Electrosurgical Excision Procedure for the Treatment of Cervical High-Grade Squamous Intraepithelial Lesions.

The loop electrosurgical excision procedure (LEEP) is a common treatment for cervical intraepithelial neoplasia (CIN). Photodynamic therapy (PDT) mediated by 5-aminolevulinic acid (ALA) is a non-invasive modality that has been used for treating precancerous diseases and HPV infections. This comparative study evaluated the efficacy and safety of ALA PDT and the LEEP in the treatment of cervical high-grade squamous intraepithelial lesions (HSILs). Patient records were reviewed and HSIL patients with HPV infections (24-51 years old) who underwent PDT or LEEP treatment were selected. Efficacy was analyzed blindly based on HPV-DNA, cytology, and colposcopy-directed biopsy obtained at 6 months after treatment. Treatment-related discomfort and side effects were also analyzed. Cure rates of 88.1% and 70.0% were achieved for the PDT group and LEEP group (p < 0.05), respectively. HPV-negative conversion rates of 81.0% and 62.0% were achieved for the PDT group and LEEP group (p < 0.05), respectively. The overall lesion remission rate of the PDT group was 19% higher than that of the LEEP group. The incidence of side effects was much lower in the PDT group. These results show that ALA PDT is a feasible non-invasive treatment for cervical HSIL.