Is high-intensity focused ultrasound a magical solution to endometriosis? A systematic review.

Background: Endometriosis presents a significant challenge in gynecological endocrinology, affecting approximately 1 in 10 women of reproductive age. Abdominal wall endometriosis (AWE) and rectosigmoid deep infiltrating endometriosis (DIE) pose unique clinical complexities. High-intensity focused ultrasound (HIFU) has emerged as a novel alternative for treating these conditions, offering a noninvasive option with potential therapeutic benefits. Methods: A systematic review was conducted following PRISMA guidelines to investigate the safety and efficacy of HIFU therapy for AWE and rectosigmoid DIE. The literature search encompassed databases from inception to January 20, 2024. Eligible studies included observational studies, case reports, and clinical trials evaluating HIFU treatment for endometriosis. Data extraction and risk of bias assessment were performed following established protocols. Results: Fourteen studies were included, comprising 330 patients with AWE and 28 patients with rectosigmoid DIE. HIFU treatment demonstrated significant efficacy, with many patients experiencing complete remission, and clinical effectiveness. Reductions in lesion volume posttreatment were consistent across studies. However, safety concerns were noted, including pain at the treatment site, hematuria, and skin burns. Adverse effects underscored the importance of careful patient selection and monitoring during HIFU therapy. Conclusion: HIFU therapy shows promise as a noninvasive approach for managing AWE and rectosigmoid DIE. While efficacy outcomes are encouraging, safety considerations warrant attention. Further research, particularly randomized controlled trials with larger sample sizes, is needed to validate findings and optimize treatment protocols.

First genetic characterization of Xeroderma pigmentosum in Libya: High frequency of XP-C founder mutation.

BACKGROUND: Xeroderma pigmentosum is an autosomal recessive disease characterized by a high sensitivity to UV radiations. The disease is clinically and genetically heterogeneous, thus making accurate early clinical diagnosis difficult. Although the disease is considered rare worldwide, previous studies have shown that it is more frequent in Maghreb countries. So far, no genetic study has been published on Libyan patients, except three reports limited to clinical descriptions. METHODS: Our study, which represents the first genetic characterization of XP in Libya, was conducted on 14 unrelated families including 23 Libyan XP patients with a consanguinity rate of 93%. Blood samples were collected from 201 individuals including patients and their relatives. Patients were screened for founder mutations already described in Tunisia. RESULTS: The two founder Maghreb XP mutations, XPA p.Arg228* associated with the neurological form and XPC p.Val548Alafs*25 in patients with only cutaneous manifestations, were homozygously identified. The latter was predominant (19 of 23 patients). In addition, another XPC homozygous mutation (p.Arg220*) has been identified in only one patient. For the remaining patient, the absence of founder XPA, XPC, XPD, and XPG mutations suggests mutational heterogeneity of XP in Libya. CONCLUSION: Identification of common mutations with other Maghreb populations is in favor of a common ancestor in North-African populations.

To What Extent the Arabic WeeFIM Is Reliable and Feasible in Egyptian Children With Burns? An Observational Cross-sectional Study.

This is an observational cross-sectional study design aimed to assess the feasibility and reliability of the Arabic version of WeeFIM in Egyptian children with healed burns with two measurements within a 2-week time period in a sample of 53 patients with healed burns who were aged 3 to 16 years and treated in the outpatient burn clinic, Faculty of Physical Therapy, Cairo University, and Om Elmisryeen Hospital. All patients who met the inclusive criteria were enrolled in the study. The adaptation of the Arabic WeeFIM instrument to an interview format suitable for burned children with communicative and/or cognitive problems and evaluation of its feasibility and reliability. The reliability was assessed by a test-retest procedure. Feasibility was evaluated by the assessment of the frequency of missing answers per item and administration time. The Arabic Index of Content Validity (was used for content validity assessment. The Arabic version of WeeFIM has borderline reliability (Cronbach's Alpha = 0.619 and Pearson correlation coefficient: r = 0.986). There was an acceptable percent to have a feasible test as 83.963% of the filled questionnaires had no missing answers and the mean of administration time was 7.4 and 5.5 for first and second assessments, respectively. The Index of Content Validity of adapted WeeFIM items showed that all the questions were relevant except for two questions only. The Arabic version of WeeFIM has high test-retest reliability, moderate internal consistency, and excellent feasibility in measuring and reporting the functional independence and burden of care for children with healed burns.

Mechanical Properties of Lightweight Foamed Concrete Modified with Magnetite (Fe3O4) Nanoparticles.

The advancement in sustainable construction has stimulated wide-ranging investigation of construction materials and practices globally. With exceptional thermal properties, fire resistance performance, excellent strength, and outstanding durability, concrete is the utmost extensively utilized construction material around the world. Taking into consideration the quantity of concrete necessary for numerous constructions works, improving concrete sustainability would be an extremely attractive potential. Lightweight foamed concrete (LFC) is tremendously permeable, and its mechanical properties weaken with a growth in the volume of voids. Air-void segregation from solid cement phases by means of aging, drainage, and merging of voids can trigger and reduce the stability and consistency of the emitted pores, making the LFC less reliable for main utilization in load-bearing components and structural elements. In turn, to augment LFC mechanical properties, the LFC cementitious matrix can be adjusted by adding various nanoparticles. The influence of magnetite nanoparticles (MNP) in LFC was not examined in the past; hence, there is some vagueness considering the mechanism to which level the MNP can affect the LFC mechanical properties. Thus, the aim of this study is to investigate the influences of MNP on the compressive, splitting tensile, and flexural LFC of 1000 kg/m3 density. Six MNP weight fractions of 0.10%, 0.15%, 0.20%, 0.25%, 0.30%, and 0.35% were considered. The parameters accessed were compressive, splitting tensile and flexural strengths. The correlation between strength parameters was established as well. The results indicated that a 0.25% weight fraction of MNP gave the best performance in terms of compressive, flexural, and splitting tensile strengths. The presence of MNP in the LFC matrix enhances the viscosity and yield stress of the mixture as well as an augmented utilization of LFC cementitious binder content, which can sustain the integrity of the wet networks hence preventing further amalgamation and aging of the voids.

Omega-3 Polyunsaturated Fatty Acids Provoke Apoptosis in Hepatocellular Carcinoma through Knocking Down the STAT3 Activated Signaling Pathway: In Vivo and In Vitro Study.

Hepatocellular carcinoma (HCC) is a common type of liver cancer and is a leading cause of death worldwide. Signal transducer and activator of transcription 3 (STAT3) is involved in HCC progression, migration, and suppression of apoptosis. This study investigates the apoptotic effect of the dietary antioxidant (n-3 PUFAs) on HepG2 cells and analyzes the underlying molecular mechanisms of this effect both in vivo and in vitro. In vivo study: Seventy-five adult male albino rats were divided into three groups (n = 25): Group I (control): 0.9% normal saline, intraperitoneal. Group II: N-Nitrosodiethylamine (200 mg/kg b.wt) intraperitoneal, followed by phenobarbital 0.05% in drinking water. Group III: as group II followed by n-3 PUFAs intubation (400 mg/kg/day). In vivo study: liver specimens for biochemical, histopathological, and immunohistochemical examination. In vitro study: MTT assay, cell morphology, PCR, Western blot, and immunohistochemical analysis. n-3 PUFAs significantly improved the histopathologic features of HCC and decreased the expression of anti-apoptotic proteins. Further, HepG2 cells proliferation was suppressed through inhibition of the STAT3 signaling pathway, cyclin D1, and Bcl-2 activity. Here we report that n-3 PUFAs may be an ideal cancer chemo-preventive candidate by targeting STAT3 signaling, which is involved in cell proliferation and apoptosis.

A study of transformer-based end-to-end speech recognition system for Kazakh language.

Today, the Transformer model, which allows parallelization and also has its own internal attention, has been widely used in the field of speech recognition. The great advantage of this architecture is the fast learning speed, and the lack of sequential operation, as with recurrent neural networks. In this work, Transformer models and an end-to-end model based on connectionist temporal classification were considered to build a system for automatic recognition of Kazakh speech. It is known that Kazakh is part of a number of agglutinative languages and has limited data for implementing speech recognition systems. Some studies have shown that the Transformer model improves system performance for low-resource languages. Based on our experiments, it was revealed that the joint use of Transformer and connectionist temporal classification models contributed to improving the performance of the Kazakh speech recognition system and with an integrated language model it showed the best character error rate 3.7% on a clean dataset.

Maximal levator resection versus Gore-Tex® sling for congenital blepharoptosis with poor levator function.

BACKGROUND: Treating congenital blepharoptosis is often mandatory to clear the visual access and avoid amblyopia; however, when the levator function is poor, achieving a satisfactory long-term outcome is challenging. This study aimed to compare the outcomes of maximal levator resection (MLR) with those of frontalis suspension (FS) using Gore-Tex ®, in the treatment of congenital blepharoptosis with poor levator function. PATIENTS AND METHODS: The study included 102 eyelids of 66 patients of mean age 4.3 ± 1.6 standard deviation (SD) years, randomly divided into two groups (51 eyes each). Group A: FS using Gore-Tex ®, Group B: MLR. Postoperative outcomes were evaluated at 1, 6 and 12 months. Patients' ophthalmic examination including margin-reflex distance (MRD1) before and after surgery and postoperative complications were recorded. RESULTS: At the end of the follow-up, the mean MRD1 increased from 0.3 ± 0.7 SD mm in Group A, 0.4 ± 0.8 SD mm in Group B preoperatively, to 2.7 ± 0.5 SD mm and 2.9 ± 0.7 SD mm, respectively (P < 0.001 in both groups). Results of Group B were significantly higher than Group A (P = 0.047). Success was achieved in 77 eyelids (75.4%), distributed as follows: 36 eyelids (70.6%) in Group A, and 41 eyelids (80.1%) in Group B. The total recurrence rate was 6.9% (seven eyes), while other complications were recorded in 23 eyes (22.5%). CONCLUSION: MLR, compared to FS with Gore-Tex® sling, can be a more efficient surgical option to correct congenital blepharoptosis with poor levator excursion. Prominent postoperative lagophthalmos warrants close ocular surface observation in early follow-up weeks.

Status of complementary and alternative medicine in the curricula of health colleges in Saudi Arabia.

OBJECTIVES: To assess the status of complementary and alternative medicine (CAM) education in health colleges in Saudi Arabia. METHODS: A cross sectional descriptive study was conducted including all medical, dentistry, pharmacy, nursing, allied medical science, and health colleges in Saudi Arabia. A semi- structured questionnaire was designed to collect information covering CAM tracks, courses and contents in the college's curricula, available postgraduates programs, continuing medical education activities, number of colleges staff members specialized or interested in CAM. RESULTS: Out of 110 health colleges in Saudi Arabia, 90 (81.1%) participated in the survey. There is no CAM specialized track or postgraduate education in any health college. Eleven (12.2%) colleges are teaching CAM courses in their curricula. Fifteen (16.7%) colleges are teaching topics related to CAM in different study subjects. Five (5.6%) colleges conducted continuing medical education (CME) activities related to CAM. Among faculty members, there are only 16 CAM specialists working in 7 colleges and 84 interested staff members, working in 20 colleges. Colleges of pharmacy are more interested in CAM education compared to other colleges with 42.9% (6/14) of them have CAM courses in their curricula, (p=0.006). Also, they have more faculty CAM specialists (p=0.026) compared to other colleges. CONCLUSION: There is a low and diverse attention given to CAM in medical education in Saudi Arabia. There is a need for a national plan to review health colleges curricula to prepare health care providers for the integration of evidenced based CAM practices.

Characterization of Wnt signaling during photoreceptor degeneration.

PURPOSE: The Wnt pathway is an essential signaling cascade that regulates multiple processes in developing and adult tissues, including differentiation, cellular survival, and stem cell proliferation. The authors recently demonstrated altered expression of Wnt pathway genes during photoreceptor death in rd1 mice, suggesting an involvement for Wnt signaling in the disease process. In this study, the authors investigated the role of Wnt signaling in retinal degeneration. METHODS: The Wnt signaling reporter mouse line Tcf-LacZ was crossed with retinal degeneration rd1 mice, and beta-galactosidase expression was used to localize Wnt signaling during photoreceptor death. To analyze the role of Wnt signaling activation, primary mixed retinal cultures were prepared, and XTT and TUNEL assays were used to quantify cell death. Luciferase reporter assays were used to measure Wnt signaling. RESULTS: The canonical Wnt signaling pathway was activated in Müller glia and the ganglion cell layer during rod photoreceptor degeneration in rd1/Tcf-LacZ mice. Wnt signaling was confirmed in cultured primary Müller glia. Furthermore, Wnt signaling activators protected photoreceptors in primary retinal cultures from H(2)O(2)-induced oxidative stress. The Wnt ligands Wnt5a, Wnt5b, Wnt10a, and Wnt13 were expressed in the degenerating retina and are candidate Wnt signaling activators in vivo. CONCLUSIONS: This study is the first demonstration that Wnt signaling is activated in the degenerating retina and that it protects retinal cultures from oxidative stress. These data suggest that Wnt signaling is a component of the glial protective response during photoreceptor injury. Therefore, inducing Wnt activation, alone or in combination with growth factors, may increase the threshold for apoptosis and halt or delay further photoreceptor degeneration.

Canonical WNT signaling during kidney development.

The canonical WNT signaling pathway plays a crucial role in patterning of the embryo during development, but little is known about the specific developmental events which are under WNT control. To understand more about how the WNT pathway orchestrates mammalian organogenesis, we studied the canonical beta-catenin-mediated WNT signaling pathway in kidneys of mice bearing a beta-catenin-responsive TCF/betaGal reporter transgene. In metanephric kidney, intense canonical WNT signaling was evident in epithelia of the branching ureteric bud and in nephrogenic mesenchyme during its transition into renal tubules. WNT signaling activity is rapidly downregulated in maturing nephrons and becomes undetectable in postnatal kidney. Sites of TCF/betaGal activity are in proximity to the known sites of renal WNT2b and WNT4 expression, and these WNTs stimulate TCF reporter activity in kidney cell lines derived from ureteric bud and metanephric mesenchyme lineages. When fetal kidney explants from HoxB7/GFP mice were exposed to the canonical WNT signaling pathway inhibitor, Dickkopf-1, arborization of the ureteric bud was significantly reduced. We conclude that restricted zones of intense canonical WNT signaling drive branching nephrogenesis in fetal kidney.

Mapping canonical Wnt signaling in the developing and adult retina.

PURPOSE: The role of the Wnt[b]/beta-catenin-dependent pathway (canonical Wnt pathway) in the context of retinal development and homeostasis is largely unknown. This study was undertaken to characterize activation of the Wnt canonical pathway and its relevance to cell type populations in the developing and adult retina. METHODS: Tissue from TCF/Lef-LacZ (T-cell-specific transcription factor/lymphoid enhancer-binding factor) transgenic mice was used for monitoring the activation of the canonical Wnt pathway. Lithium (Li(+)) treatment was applied to induce ectopic activation of the TCF/Lef-LacZ reporter gene in retinal explants. Gene expression and retinal cell types were examined by in situ hybridization (ISH) or by immunohistochemistry (IHC). RESULTS: On Li(+) treatment, ectopic expression of the TCF/Lef-LacZ reporter gene was rapidly and dramatically induced in retinal explants. The pattern of TCF/Lef-LacZ reporter gene expression was dynamic throughout retinal development and in the adult retina. There was a distinctive expression pattern in each cellular layer, in the developing ciliary margin (CM), and the prospective ciliary epithelium. In the mature retina, the TCF/Lef-LacZ reporter gene was expressed in subsets of retinal ganglion cells (RGCs) and amacrine cells. The expression of the four TCF/Lef transcription factors overlapped with activation of the TCF/Lef-LacZ reporter. CONCLUSIONS: The TCF/Lef-LacZ transgene is a faithful reporter of canonical Wnt signaling in the retina. The pattern of TCF/Lef-LacZ reporter gene activation and of TCF/Lef transcription factor expression suggests that activation of the canonical Wnt pathway is developmental-stage dependent and is spatially modulated. Our findings also imply the involvement of this pathway in the specification and/or generation of ciliary epithelium, cellular differentiation, axon guidance, and connectivity to targets in the central nervous system and in the maintenance or function of specific retinal neurons in the adult.

Beta-catenin activation is necessary and sufficient to specify the dorsal dermal fate in the mouse.

Dorsal dermis and epaxial muscle have been shown to arise from the central dermomyotome in the chick. En1 is a homeobox transcription factor gene expressed in the central dermomyotome. We show by genetic fate mapping in the mouse that En1-expressing cells of the central dermomyotome give rise to dorsal dermis and epaxial muscle and, unexpectedly, to interscapular brown fat. Thus, the En1-expressing central dermomyotome normally gives rise to three distinct fates in mice. Wnt signals are important in early stages of dermomyotome development, but the signal that acts to specify the dermal fate has not been identified. Using a reporter transgene for Wnt signal transduction, we show that the En1-expressing cells directly underneath the surface ectoderm transduce Wnt signals. When the essential Wnt transducer beta-catenin is mutated in En1 cells, it results in the loss of Dermo1-expressing dorsal dermal progenitors and dermis. Conversely, when beta-catenin was activated in En1 cells, it induces Dermo1 expression in all cells of the En1 domain and disrupts muscle gene expression. Our results indicate that the mouse central dermomyotome gives rise to dermis, muscle, and brown fat, and that Wnt signalling normally instructs cells to select the dorsal dermal fate.

Wnt signals mediate a fate decision between otic placode and epidermis.

The otic placode, the anlagen of the inner ear, develops from an ectodermal field characterized by expression of the transcription factor Pax2. Previous fate mapping studies suggest that these Pax2(+) cells will give rise to both otic placode tissue and epidermis, but the signals that divide the Pax2(+) field into placodal and epidermal territories are unknown. We report that Wnt signaling is normally activated in a subset of Pax2(+) cells, and that conditional inactivation of beta-catenin in these cells causes an expansion of epidermal markers at the expense of the otic placode. Conversely, conditional activation of beta-catenin in Pax2(+) cells causes an expansion of the otic placode at the expense of epidermis, and the resulting otic tissue expresses exclusively dorsal otocyst markers. Together, these results suggest that Wnt signaling acts instructively to direct Pax2(+) cells to an otic placodal, rather than an epidermal, fate and promotes dorsal cell identities in the otocyst.

Uterine Wnt/beta-catenin signaling is required for implantation.

Successful implantation relies on precisely orchestrated and reciprocal signaling between the implanting blastocyst and the receptive uterus. We have examined the role of the Wnt/beta-catenin signaling pathway during the process of implantation and demonstrate that this pathway is activated during two distinct stages. Wnt/beta-catenin signaling is first transiently activated in circular smooth muscle forming a banding pattern of activity within the uterus on early day 4. Subsequently, activation is restricted to the luminal epithelium at the prospective site of implantation. Activation at both sites requires the presence of the blastocyst. Furthermore, inhibition of Wnt/beta-catenin signaling interferes with the process of implantation. Our results demonstrate that the Wnt/beta-catenin signaling pathway plays a central role in coordinating uterus-embryo interactions required for implantation.

Beta-catenin signaling marks the prospective site of primitive streak formation in the mouse embryo.

Beta-catenin signaling has been shown to be involved in triggering axis formation in several organisms, including Xenopus and zebrafish. Genetic analysis has demonstrated that the Wnt/beta-catenin signaling pathway is also involved in axis formation in the mouse, since a targeted deletion of beta-catenin results in embryos that have a block in anterior-posterior axis formation, fail to initiate gastrulation, and do not form mesoderm. However, because beta-catenin is ubiquitously expressed, the precise time and cell types in which this signaling pathway is active during early embryonic development remain unknown. Thus, to better understand the role of the Wnt/beta-catenin signaling pathway in axis formation and mesoderm specification, we have examined both the distribution and signaling activity of beta-catenin during early embryonic development in the mouse. We show that the N-terminally nonphosphorylated form of beta-catenin as well as beta-catenin signaling is first detectable in the extraembryonic visceral endoderm in day 5.5 embryos. Before the initiation of gastrulation at day 6.0, beta-catenin signaling is asymmetrically distributed within the epiblast and is localized to a small group of cells adjacent to the embryonic--extraembryonic junction. At day 6.5 and onward, beta-catenin signaling was detected in the primitive streak and mature node. Thus, beta-catenin signaling precedes primitive streak formation and is present in epiblast cells that will go on to form the primitive streak. These results support a critical role for the Wnt/beta-catenin pathway in specifying cells to form the primitive streak and node in the mammalian embryo as well as identify a novel domain of Wnt/beta-catenin signaling activity during early embryogenesis.

Expression and estradiol regulation of Wnt genes in the mouse blastocyst identify a candidate pathway for embryo-maternal signaling at implantation.

Implantation of mammalian embryos depends on differentiation of the blastocyst to a competent state and of the uterine endometrium to a receptive state. Communication between the blastocyst and uterus ensures that these changes are temporally coordinated. Although considerable evidence indicates that the blastocyst induces expression of numerous genes in uterine tissue, potential signaling mechanisms have yet to be identified. Moreover, whereas a surge of maternal estradiol occurring on Day 4 of pregnancy in the mouse is critically required for many of the peri-implantation uterine changes, whether this surge also affects blastocyst gene expression has not been established. We show here that mouse morulae express genes encoding several members of the Wnt family of signaling molecules. Additional Wnt genes are newly expressed following development to blastocyst. Unexpectedly, Wnt5a and Wnt11 are expressed in embryos that undergo the morula-to-blastocyst transition in vivo, but only weakly or not at all in embryos that do so in vitro. Upregulation of Wnt11 is temporally coordinated with the surge of maternal estradiol on Day 4. Wnt11 fails to be upregulated in blastocysts obtained from mice ovariectomized early on Day 4 or from mice treated with the estradiol antagonist, ICI 182,780. Administration of estradiol-17beta or its metabolite, 4-OH-estradiol, to ovariectomized mice restores Wnt11 expression. Moreover, Wnt11 expression is not upregulated when blastocysts are trapped in the oviduct following ligation of the utero-tubal junction, nor when estradiol-17beta or 4-OH-estradiol are administered to blastocysts in vitro. These results establish a comprehensive profile of Wnt gene expression during late preimplantation development, demonstrate that estradiol regulates gene expression in the blastocyst via uterine factors, and identify Wnts as potential mediators of embryo-uterine communication during implantation.

Characterization of Wnt signaling components and activation of the Wnt canonical pathway in the murine retina.

The neuroepithelial layer of the developing eyecup contains multipotential precursor cells that give rise to all of the neurons and the one glial cell type present in the adult retina. Patterning within the retinal neuroepithelium is regulated by cell intrinsic as well as cell extrinsic mechanisms. Although the identity of some of the signaling molecules that regulate retinal development is known, the function of many others, especially members of the Wnt family, has yet to be characterized in the context of retinal development. We undertook a comprehensive in situ hybridization analysis to examine the expression of Wnt pathway components in the developing and adult mouse neural retina. Our findings confirm and extend previous expression studies in mice and other vertebrates, as we show that Wnt-3, -5a, -5b, and -7b are expressed in the neural retina and that there is a dynamic pattern of Wnt receptor (Mouse frizzled [Mfz]) and Wnt antagonist (Secreted-frizzled-related protein [Sfrp]) gene expression in the embryonic and perinatal neural retina. Moreover, we show that Wnt-13 is expressed in the pigment epithelium overlying the distal part of the eyecup and the ciliary margin and that Mfz-4, -6, and -7 are expressed in different regions within the ciliary margin. To determine where activation of canonical Wnt signaling is occurring in the retina, we examined reporter gene expression in TCF/Lef-LacZ mice and we demonstrate that the highest levels of beta-gal activity are found in the ciliary margin, adjacent to and within the Wnt-13 expression domain, implicating Wnt-13 signaling in the development of the ciliary margin and its derivatives.