Number of serotonergic neurons in the subthalamic nucleus and globus pallidus internus could influence the effects of deep brain stimulation in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) is a standard treatment for Parkinson's disease (PD), with both regions exhibiting similar treatment effectiveness. However, posttreatment neuropsychiatric side effects, such as severe depression, are common, primarily due to the loss of serotonergic cells. Identifying a region with fewer serotonergic neurons could potentially reduce these side effects. This study aimed to quantify the number of serotonergic neurons in the STN and GPi. Both regions were analyzed using hematoxylin and eosin staining and immunohistochemistry. The GPi exhibited a significantly lower number and H-score of serotonergic neurons than the STN. Within the STN, the number and H-score of serotonergic neurons were higher in the medial aspect than in the lateral aspect. Three different types of neurons, large and small, were observed. In STN, large neurons were concentrated in the center and small neurons in the periphery. This distribution was not observed in GPi. In addition, the concentration of the serotonergic neurons is less in GPi. These findings suggest that the GPi may be a safer target region, potentially reducing the incidence of post-DBS depression.

Pseudoxanthomatous Salpingitis: A Rare Granulomatous Pathology of the Fallopian Tube.

Uncommon presentations of granulomatous salpingitis are pseudoxanthoma salpingitis (PSX) and xanthogranulomatous salpingitis (XGS). The clinical features and image modalities can mimic ovarian malignancy. Thus, a proper pre-operative evaluation of this entity is vital to avoid radical treatment. Here, we report a case of a 31-year-old woman with primary infertility diagnosed with pseudoxanthoma salpinx. This patient was a known case of endometriosis and presented with gross ascites.

Mapping ACE2 and TMPRSS2 co-expression in human brain tissue: implications for SARS-CoV-2 neurological manifestations.

The Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily targets respiratory cells, but emerging evidence shows neurological involvement, with the virus directly affecting neurons and glia. SARS-CoV-2 entry into a target cell requires co-expression of ACE2 (Angiotensin-converting enzyme-2) and TMPRSS2 (Trans membrane serine protease-2). Relevant literature on human neurological tissue is sparse and mostly focused on the olfactory areas. This prompted our study to map brain-wide expression of these entry proteins and assess age-related changes. The normal brain tissue samples were collected from cerebral cortex, hippocampus, basal ganglia, thalamus, hypothalamus, brain stem and cerebellum; and were divided into two groups - up to 40 years (n = 10) and above 40 years (n = 10). ACE2 and TMPRSS2 gene expression analysis was done using qRT-PCR and protein co-expression was seen by immunofluorescence. The ACE2 and TMPRSS2 gene expression was observed to be highest in hypothalamus and thalamus regions, respectively. Immunoreactivity for both ACE-2 and TMPRSS2 was observed in all examined brain regions, confirming the presence of these viral entry receptors. Co-localisation was maximum in hypothalamus. Our study did not find any trend related to different age groups. The expression of both these viral entry receptors suggests that normal human brain is susceptibility to SARS-CoV-2, perhaps which could be related to the cognitive and neurological impairment that occur in patients.

Impact of crystalline domains on long-term stability and mechanical performance of anisotropic silk fibroin sponges.

Sponge-like materials made from regenerated silk fibroin biopolymers are a tunable and advantageous platform for in vitro engineered tissue culture and in vivo tissue regeneration. Anisotropic, three-dimensional (3D) silk fibroin sponge-like scaffolds can mimic the architecture of contractile muscle. Herein, we use silk fibroin solution isolated from the cocoons of Bombyx mori silkworms to form aligned sponges via directional ice templating in a custom mold with a slurry of dry ice and ethanol. Hydrated tensile mechanical properties of these aligned sponges were evaluated as a function of silk polymer concentration (3% or 5%), freezing time (50% or 100% ethanol), and post-lyophilization method for inducing crystallinity (autoclaving, water annealing). Hydrated static tensile tests were used to determine Young's modulus and ultimate tensile strength across sponge formulations at two strain rates to evaluate rate dependence in the calculated parameters. Results aligned with previous reports in the literature for isotropic silk fibroin sponge-like scaffolds, where the method by which beta-sheets were formed and level of beta-sheet content (crystallinity) had the greatest impact on static parameters, while polymer concentration and freezing rate did not significantly impact static mechanical properties. We estimated the crystalline organization using molecular dynamics simulations to show that larger crystalline regions may be responsible for strength at low strain amplitudes and brittleness at high strain amplitudes in the autoclaved sponges. Within the parameters evaluated, extensional Young's modulus is tunable in the range of 600-2800 kPa. Dynamic tensile testing revealed the linear viscoelastic region to be between 0% and 10% strain amplitude and 0.2-2 Hz frequencies. Long-term stability was evaluated by hysteresis and fatigue tests. Fatigue tests showed minimal change in the storage and loss modulus of 5% silk fibroin sponges for more than 6000 min of continuous mechanical stimulation in the linear regime at 10% strain amplitude and 1 Hz frequency. Furthermore, we confirmed that these mechanical properties hold when decellularized extracellular matrix is added to the sponges and when the mechanical property assessments were performed in cell culture media. We also used nano-computed tomography (nano-CT) and simulations to explore pore interconnectivity and tortuosity. Overall, these results highlight the potential of anisotropic, sponge-like silk fibroin scaffolds for long-term (>6 weeks) contractile muscle culture with an in vitro bioreactor system that provides routine mechanical stimulation.

Fertility and Obstetric Outcomes of Assisted Reproductive Technology (ART) in Women With Adenomyosis Following Gonadotropin-Releasing Hormone Agonist Therapy: A Single-Center Experience.

INTRODUCTION: Adenomyosis is an ambiguous disorder causing a wide variety of implications from dysmenorrhea, heavy menstrual bleeding, and infertility to pregnancy complications. Adenomyosis is associated with altered endocrine and inflammatory milieu, resulting in impaired implantation and reduced fertility potential. It is also associated with increased incidence of obstetric complications such as miscarriage, antepartum hemorrhage, placental mal-position, hypertensive disorders, small for gestational age-intrauterine growth restriction (SGA-IUGR), cesarean section, preterm labor, preterm premature rupture of membranes (PPROM), and neonatal intensive care unit (NICU) admissions. OBJECTIVE: The aim of our study was to investigate the fertility and obstetric outcomes in women with adenomyosis treated with GnRH agonists compared to controls with normal uteri undergoing in-vitro fertilization (IVF) at our center, thereby establishing the role of gonadotropin-releasing hormone (GnRH) agonists in managing sub-fertile women with adenomyosis. MATERIALS AND METHODS: We carried out a retrospective cohort study at our hospital to analyze the effects of adenomyosis on IVF and pregnancy outcomes. This study (n=83) involves women with adenomyosis between the ages of 21 and 37 years who were followed up at our center between 2013 and 2022. The controls (n=83) were selected from women who underwent IVF-intracytoplasmic sperm injection (IVF-ICSI) for tubal or mild male factor infertility with normal appearing uterus within the same time frame. Women with adenomyosis were given GnRH agonist as long/ultralong agonist protocol before controlled ovarian stimulation or as down-regulated frozen embryo transfer (FET). The length of suppression was between one and six months based on the size of the uterus and response to treatment. Fertility and obstetric outcomes were analyzed. RESULTS: The implantation rates were found to be equivocal: 54.2% and 53% in the adenomyosis and control groups, respectively (p=0.208). The cumulative live birth rate was 50.6% and 48.2% in the study and control groups, respectively (p=0.341). The biochemical pregnancy rate and the first- and second-trimester miscarriage rates were not significantly different between the group with adenomyosis and the group with normal uterus. The incidence of preterm deliveries and antepartum hemorrhage was found to be significantly increased in the study group. CONCLUSION: Medical management in women with adenomyosis optimizes the live birth rates giving results at par with the control population.

Central myelin-peripheral myelin junction in trigeminal, facial, and vestibulocochlear nerve: A histo-morphometric study.

BACKGROUND: The study aimed to locate the central myelin and peripheral myelin junction (CNS PNS Junction, CPJ) in trigeminal, facial and vestibulocochlear nerves. METHODS: The cisternal segments of the nerves were cut from the brainstem to the proximal margin of trigeminal ganglia (trigeminal nerve) and internal acoustic meatus (facial and vestibulocochlear nerve) from cadavers. Horizontal sections of H&E stained slides were analysed and histo morphometry was performed. The CPJ was confirmed by immunohistochemistry using monoclonal myelin basic protein antibody. RESULTS: The mean length of the trigeminal, facial and vestibulocochlear nerves were 13.6 ± 3.1 mm, 12.4 ± 1.9 mm and 11.5 ± 2.0 mm respectively; mean length of the centrally myelinated segment at the point of maximum convexity was 4.1 ± 1.5 mm, 3.7 ± 1.6 mm, 3.6 ± 1.4 mm respectively. Six different patterns were observed fortheCPJ.Utilizing the derived values, the CPJwas located at a distance of 18 - 48% and 17 - 61% of the total length of the nerve in all the cases in trigeminal and facial nerve respectively. In vestibulocochlear nerve, it was located at a distance of about 13 - 54% of the total length of the nerve. CONCLUSIONS: The location of the CPJ in the vestibulocochlear nerve was midway between the brainstem and internal acoustic meatus which is a novel observation.For all the nerves, the CPJ was located either at or before the half way along the length of the nerve in huge majority (97%); never crossing the 60% of the nerve length.

Socioscientific Issues Thinking and Action in the Midst of Science-in-the-Making.

Like all SSI, the COVID-19 pandemic requires decisions that are contentious, involve scientific thinking, and vary across social groups. This investigation determined how perceptions about COVID-19 science and sociocultural membership associate with 557 university biology students': (1) COVID-19 behaviors after stay-at-home orders and (2) support for future societal COVID-19 responses. Hierarchical moderated multiple regression analyses demonstrate that students' COVID-19 mitigating actions after stay-at-home orders were significantly and positively associated with, in order of importance: (1) higher levels of COVID-19 spread prevention knowledge; (2) espousing more liberal, as opposed to conservative, political orientations; (3) being female; and (4) increased disbelief of COVID-19 misinformation/disinformation claims. Furthermore, the students' political orientation moderated the relationship between their trust in scientific models to guide COVID-19 decisions and their personal COVID-19 actions, with trust in scientific models to guide COVID-19 decision-making being a significant positive predictor of moderate, conservative, and very conservative student groups' COVID-19 mitigating actions. Conversely, there was no association between trust in scientific models to guide COVID-19 decision-making and very liberal and liberal students' conducting COVID-19 actions. Hierarchical moderated multiple regression analyses revealed that students' support for societal-wide COVID-19 mitigating measures going forward is positively associated with, in order of importance: (1) espousing more liberal, as opposed to conservative, political orientations; (2) higher levels of COVID-19 spread prevention knowledge; (3) increased disbelief of COVID-19 misinformation/disinformation claims; (4) trust in scientific models for guiding COVID-19 decision-making; and (5) beliefs that factors beyond science and technology (e.g., personal actions) are necessary for pandemic resolution. Implications discussed include the importance for helping students analyze how sociocultural membership, personal biases, and trust in science interactively influence socioscientific decision-making. Further recommendations discussed include how science communication strategies must account for sociocultural variance in order to optimize trust in science and reasoned and responsible action.

Synthesis and characterization of thiol-acrylate hydrogels using a base-catalyzed Michael addition for 3D cell culture applications.

There is significant interest in developing new approaches for culturing mammalian cells in a three-dimensional (3D) environment due to the fact that it better recapitulates the in vivo environment. The goal of this work was to develop thiol-acrylate, biodegradable hydrogels that possess highly tunable properties to support in vitro 3D culture. Six different hydrogel formulations were synthesized using two readily available monomers, a trithiol (ETTMP 1300 [ethoxylated trimethylolpropane tri(3-mercaptopropionate) 1300]) and a diacrylate (PEGDA 700 [polyethylene glycol diacrylate 700]), polymerized by a base-catalyzed Michael addition reaction. The resultant hydrogels were homogeneous, hydrophilic, and biodegradable. Different mechanical properties such as gelation time, storage modulus (or the elasticity G'), swelling ratio, and rate of degradation were tuned by varying the weight percentage of polymer, the molar ratio of thiol-to-acrylate groups, and the pH of the solution. Cytocompatibility was assessed using two model breast cancer cell lines by both 2D and 3D cell culturing approaches. The hydrogel formulations with a thiol-to-acrylate molar ratio of 1.05 were found to be optimal for both 2D and 3D cultures with MDA-MB-231 cellular aggregates found to be viable after 17 days of 3D continuous culture. Finally, MCF7 cells were observed to form 3D spheroids up to 600 µm in diameter as proof of principle for the thiol-acrylate hydrogel to function as a scaffold for in vitro 3D cell culture. A comparison of the different mechanical properties of the six hydrogel formulations coupled with in vitro cell culture results and findings from previously published hydrogels conclude that the thiol-acrylate hydrogels have significant potential as a scaffold for 3D cell culture.

Novel Factors of Viral Origin Inhibit TOR Pathway Gene Expression.

Polydnaviruses (PDVs) are obligate symbionts of endoparasitoid wasps, which exclusively attack the larval stages of their lepidopteran hosts. The Polydnavirus is injected by the parasitoid female during oviposition to selectively infect host tissues by the expression of viral genes without undergoing replication. Toxoneuron nigriceps bracovirus (TnBV) is associated with Toxoneuron nigriceps (Hymenoptera: Braconidae) wasp, an endoparasitoid of the tobacco budworm larval stages, Heliothis virescens (Lepidoptera: Noctuidae). Previous studies showed that TnBV is responsible for alterations in host physiology. The arrest of ecdysteroidogenesis is the main alteration which occurs in last (fifth) instar larvae and, as a consequence, prevents pupation. TnBV induces the functional inactivation of H. virescens prothoracic glands (PGs), resulting in decreased protein synthesis and phosphorylation. Previous work showed the involvement of the PI3K/Akt/TOR pathway in H. virescens PG ecdysteroidogenesis. Here, we demonstrate that this cellular signaling is one of the targets of TnBV infection. Western blot analysis and enzyme immunoassay (EIA) showed that parasitism inhibits ecdysteroidogenesis and the phosphorylation of the two targets of TOR (4E-BP and S6K), despite the stimulation of PTTH contained in the brain extract. Using a transcriptomic approach, we identified viral genes selectively expressed in last instar H. virescens PGs, 48 h after parasitization, and evaluated expression levels of PI3K/Akt/TOR pathway genes in these tissues. The relative expression of selected genes belonging to the TOR pathway (tor, 4e-bp, and s6k) in PGs of parasitized larvae was further confirmed by qRT-PCR. The down-regulation of these genes in PGs of parasitized larvae supports the hypothesis of TnBV involvement in blocking ecdysteroidogenesis, through alterations of the PI3K/Akt/TOR pathway at the transcriptional level.

Ecdysteroidogenesis and development in Heliothis virescens (Lepidoptera: Noctuidae): Focus on PTTH-stimulated pathways.

Post-embryonic development and molting in insects are regulated by endocrine changes, including prothoracicotropic hormone (PTTH)-stimulated ecdysone secretion by the prothoracic glands (PGs). In Lepidoptera, two pathways are potentially involved in PTTH-stimulated ecdysteroidogenesis, mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase/protein kinase B/target of rapamycin (PI3K/Akt/TOR). We investigated the potential roles of both these pathways in Heliothis virescens ecdysteroidogenesis. We identified putative proteins belonging to MAPK and PI3K/Akt/TOR signaling cascades, using transcriptomic analyses of PGs from last (fifth) instar larvae. Using western blots, we measured the phosphorylation of 4E-BP and S6K proteins, the main targets of TOR, following the in vitro exposure of PGs to brain extract containing PTTH (hereafter referred to as PTTH) and/or the inhibitors of MAPK (U0126), PI3K (LY294002) or TOR (rapamycin). Next, we measured ecdysone production, under the same experimental conditions, by enzyme immunoassay (EIA). We found that in Heliothis virescens last instar larvae, both pathways modulated PTTH-stimulated ecdysteroidogenesis. Finally, we analyzed the post-embryonic development of third and fourth instar larvae fed on diet supplemented with rapamycin, in order to better understand the role of the TOR pathway in larval growth. When rapamycin was added to the diet of larvae, the onset of molting was delayed, the growth rate was reduced and abnormally small larvae/pupae with high mortality rates resulted. In larvae fed on diet supplemented with rapamycin, the growth of PGs was suppressed, and ecdysone production and secretion were inhibited. Overall, the in vivo and in vitro results demonstrated that, similarly to Bombyx mori, MAPK and PI3K/Akt/TOR pathways are involved in PTTH signaling-stimulated ecdysteroidogenesis, and indicated the important role of TOR protein in H. virescens systemic growth.

Significance of likes: Analysing passive interactions on Facebook during campaigning.

With more and more political candidates using social media for campaigning, researchers are looking at measuring the effectiveness of this medium. Most research, however, concentrates on the bare count of likes (or twitter mentions) in an attempt to correlate social media presence and winning. In this paper, we propose a novel method, Interaction Strength Plot (IntS) to measure the passive interactions between a candidate's posts on Facebook and the users (liking the posts). Using this method on original Malaysian General Election (MGE13) and Australian Federal Elections (AFE13) Facebook Pages (FP) campaign data, we label an FP as performing well if both the posting frequency and the likes gathered are above average. Our method shows that over 60% of the MGE13 candidates and 85% of the AFE13 candidates studied in this paper had under-performing FP. Some of these FP owners would have been identified as popular based on bare count. Thus our performance chart is a vital step forward in measuring the effectiveness of online campaigning.

Synthesis of thiazolidine-2,4-dione derivatives: anticancer, antimicrobial and DNA cleavage studies.

In the search of efficient anticancer agents, here, new 5-(4-alkylbenzyledene)thiazolidine-2,4-dione derivatives (5a-g) have been successfully synthesized and characterized and are evaluated for anticancer and antimicrobial activities using DNA cleavage studies. In vitro studies on anticancer activity of compound 5d (NSC: 768619/1) was done against the full panel of 60 human tumor cell lines. The five-level dose activity results revealed that, the compound 5d was active against all the cell lines, it has shown potential activity against leukemia SR (GI50: 2.04 µM), non-small cell lung cancer NCI-H522 (GI50: 1.36 µM), colon cancer COLO 205 (GI50: 1.64 µM), CNS cancer SF-539 (GI50: 1.87 µM), melanoma SK-MEL-2 (GI50: 1.64 µM), ovarian cancer OVCAR-3 (GI50: 1.87 µM), renal cancer RXF 393 (GI50: 1.15 µM), prostate cancer PC-3 (GI50: 1.90 µM), and breast cancer MDA-MB-468(GI50: 1.11 µM). DNA cleavage studies revealed that at 50 µg/mL concentration, partial DNA digestion was observed and when the concentration is increasing to threefold (150 µg/mL), complete linear DNA digestion and partial supercoiled DNA digestion was observed. Further antimicrobial studies indicate that all the synthesized compounds except compound 5a possess prominent activity against all the screened microbial species. This study throws a ray of light in the field of anticancer drugs.

Photochemical synthesis and anticancer activity of barbituric acid, thiobarbituric acid, thiosemicarbazide, and isoniazid linked to 2-phenyl indole derivatives.

2-Phenyl-1H-indole-3-carbaldehyde-based barbituric acid, thiobarbituric acid, thiosemicarbazide, isoniazid, and malononitrile derivatives were synthesized under photochemical conditions. The antitumor activities of the synthesized compounds were evaluated on three different human cancer cell lines representing prostate cancer cell line DU145, Dwivedi (DWD) cancer cell lines, and breast cancer cell line MCF7. All the screened compounds possessed moderate anticancer activity, and out of all the screened compounds, 5-{1[2-(4-chloro-phenyl)2-oxo-ethyl]-2-phenyl-1H-indole-3-ylmethylene}-2-thioxo-dihydro-pyrimidine-4,6-dione (2b) and 5-{1[2-(4-methoxy-phenyl)2-oxo-ethyl]-2-phenyl-1H-indole-3-ylmethylene}-2-thioxo-dihydro-pyrimidine-4,6-dione (2d) exhibited marked antitumor activity against used cell lines. Additionally, barbituric acid derivatives were selective to inhibit cell line DWD and breast cancer cell lines.

Pregnancy outcome with coexisting mole after intracytoplasmic sperm injection: A case series.

Partial/complete hydatidiform mole with coexisting fetus is a rare condition. Optimal management is a challenge that remains a dilemma since these pregnancies are associated with maternal as well as fetal complications including hemorrhage, preeclampsia, thromboembolic disease, intra uterine demise and increased risk of persistent trophoblastic disease. Here we report 2 cases of partial mole with live fetus after ICSI and a case of complete mole with coexisting fetus after ICSI in a turner mosaic that resulted in a live birth.

The probable significance of tracheal tufts in the 8th abdominal segment of Heliothis virescens (F.) on the development of its parasitoid, Toxoneuron nigriceps (Viereck).

The 8th abdominal segment of Heliothis virescens (Fabricius) larvae contains aerating trachea and tracheole tufts that end in the hemocoel of the 8th segment, unlike the tracheae that invade tissues in other segments. These tracheal tufts from the 8th abdominal segment extend to the tokus region, which along with the telson cavity is known to act as a "lung" for hemocytes in Calpodes ethlius and a few other lepidopteran larvae. The goal of this research was to study the effects of these tracheal tufts in the 8th abdominal segment on parasitoid development inside the host larvae, H. virescens. The first objective was to determine if the eggs of the parasitoid, Toxoneuron nigriceps, are predominantly located among the tracheal tufts of the 8th abdominal segment compared to other body cavity regions irrespective of their oviposition site or the position of the host larvae. The results showed that several hours after oviposition most of the eggs are found in the 8th abdominal segment irrespective of the oviposition site or the position of the host larvae. The second objective was to study the effect of varying oxygen concentrations in vitro on various developmental stages of the egg. The results showed that decreasing oxygen concentrations adversely affects the parasitoid egg development in vitro. A third objective was to determine the oxygen concentration in 8th abdominal segment of the host larvae and compare it to other regions of the body using an oxygen sensor placed in vivo. The results suggested relatively high concentration of oxygen in the 8th abdominal segment compared to other regions of the host, thus supporting our hypothesis that the increased oxygen level in the 8th abdominal segment is important to the development of the parasitoid eggs.