Caenorhabditis elegans neuropeptide NLP-27 enhances neurodegeneration and paralysis in an opioid-like manner during fungal infection.

The nervous system of metazoans is involved in host-pathogen interactions to control immune activation. In Caenorhabditis elegans, this includes sleep induction, mediated by neuropeptide-like proteins (NLPs), which increases the chance of survival after wounding. Here we analyzed the role of NLP-27 in the infection of C. elegans with the nematode-trapping fungus Arthrobotrys flagrans. Early responses of C. elegans were the upregulation of nlp-27, the induction of paralysis (sleep), and neurodegeneration of the mechanosensing PVD (Posterior Ventral Process D) neurons. Deletion of nlp-27 reduced neurodegeneration during fungal attack. Induction of nlp-27 was independent of the MAP kinase PMK-1, and expression of nlp-27 in the hypodermis was sufficient to induce paralysis, although NLP-27 was also upregulated in head neurons. NLP-27 contains the pentapeptide YGGYG sequence known to bind the human µ- and κ-type opioid receptors suggesting NLP-27 or peptides thereof act on opioid receptors. The opioid receptor antagonist naloxone shortened the paralysis time like overexpression of NLP-27.

Requests for vulvoplasty as gender-affirming surgery: a cross-sectional study in Denmark.

BACKGROUND: Vulvoplasty, described as a promising procedure for transgender and gender diverse (TGD) persons who were assigned male at birth and who, for example, do not need a vagina or who have contraindications to vaginoplasty, is a procedure that in accordance with current guidelines is not offered as genital gender-affirming surgery in Denmark. AIM: In this study we sought to quantify the need for offering vulvoplasty in Denmark. MATERIALS AND METHODS: An online questionnaire was developed. The target group included TGD persons who were assigned male at birth and a minimum of 18 years old. Prior to data collection, the questionnaire was tested with stakeholders from the target group and was subsequently distributed exclusively in closed groups and online fora for TGD persons. Data collection took place from September 1 to October 31, 2022. OUTCOMES: Primary outcomes were type of bottom surgery respondents preferred, when vulvoplasty was chosen, the reason(s) for choosing it. RESULTS: A total of 152 responses were included for data analysis, and 134 records were complete responses. Out of 134 respondents, 35 (26.1%) preferred vulvoplasty. The reasons for preferring vulvoplasty were the belief that there is less risk with the procedure (71%), followed by not wanting to dilate (54%), no need for a vagina (48%), and no need for vaginal penetration (40%). Health issues or other reasons were infrequent (5%). Out of 122 respondents who had not had prior bottom surgery, 106 (86.9%) wanted it in the future. CLINICAL IMPLICATIONS: Some TGD individuals in Denmark could benefit from vulvoplasty and would choose it if offered. STRENGTHS AND LIMITATIONS: Strengths of this study were that the questionnaire was thoroughly tested prior to application and that the survey could only be accessed via closed fora and groups for TDG persons. Limitations were that the sample size was small, and that the response rate could not be estimated. CONCLUSION: The results of this study imply that there is an unmet need for vulvoplasty, and bottom surgery in general, in Denmark.

Characteristics of submerged and partially submerged caves (habitat type 8330) in Romania.

Underwater sea caves form a relatively under-examined habitat type within the marine regions of Europe, although they provide unique physical conditions such as reduced light and wave energy, in addition to reduced temperature amplitude. This study aimed at revealing the characteristics of submerged cavities on the southern Romanian continental shelf where six protected areas exist. We used high-resolution bathymetry data and side-scan sonar imaging to identify limestone outcrops where cavities would be most probable to form and then performed visual observation during SCUBA diving activities. We found that submerged cavities appear in all marine-protected areas and their neighboring unprotected areas from the shore to ~20-m depth mostly in the form of caverns, niches, and overhangs that meet the physical requirements of the habitat type 8330 as defined by the European Commission. We propose that habitat type 8330 should be listed in the Natura 2000 Standard Data Forms of the protected areas where it is missing, and we also propose that some protected areas should be expanded to include important areas with the occurrence of this habitat type. Finally, we note here for the first time the occurrence of Movile-type karst and an associated sulfidic water spring on the southern shore of Lake Techirghiol, similar to the region near Mangalia where it was first described in the literature. Although our finding prompts for a more detailed study, it indicates the existence of an underground ecosystem similar to that from the well-studied Movile Cave, but isolated by a distance of over 20 km.

Intracranial epidermoid cysts: benign entities with malignant behavior: experience with 36 cases.

Intracranial epidermoid cysts are benign slow-growing ectodermal inclusions that account for less than 1% of all intracranial tumors. We retrospectively reviewed 36 such cases to evaluate the demographic characteristics, clinical manifestations, anatomical distribution, surgical management, and treatment outcome of these tumors. Additionally, we sought to identify the relationship between median or paramedian cistern tumor localization and clinical parameters, such as recurrence risk, hospitalization duration, and postoperative complication rates. The most frequently observed neurological symptoms were transient headaches (77.8%), dizziness (36.1%), CN VII palsy (19.4%), CN VIII hearing difficulty (19.4%) and cerebellar signs (19.4%). The most common surgical approaches included retrosigmoid (36.1%), subfrontal (19.4%) and telovelar (19.4%) approaches; gross total resection was feasible in 83.3% of cases. The postoperative complication rate was 38.9%. Tumors were more frequently found in the paramedian cisterns (47.2%), followed by the median line cisterns (41.6%). Multivariate analysis revealed that postoperative hydrocephalus and age < 40 years were prognostic factors for tumor recurrence. Median-like tumor location was a risk factor for the presence of symptomatic hydrocephalus both preoperatively and postoperatively, increasing the likelihood of protracted hospitalization (> 10 days). Despite their benign histopathological nature, these tumors have an important clinical resonance, with a high rate of postoperative complications and a degree of recurrence amplified by younger age and hydrocephalus.

Sustainable Packaging Design for Molded Expanded Polystyrene Cushion.

A molded expanded polystyrene (EPS) cushion is a flexible, closed-cell foam that can be molded to fit any packing application and is effective at absorbing shock. However, the packaging waste of EPS cushions causes pollution to landfills and the environment. Despite being known to cause pollution, this sustainable packaging actually has the potential to reduce this environmental pollution because of its reusability. Therefore, the objective of this study is to identify the accurate design parameter that can be emphasized in producing a sustainable design of EPS cushion packaging. An experimental method of drop testing and design simulation analysis was conducted. The effectiveness of the design parameters was also verified. Based on the results, there are four main elements that necessitate careful consideration: rib positioning, EPS cushion thickness, package layout, and packing size. These parameter findings make a significant contribution to sustainable design, where these elements were integrated directly to reduce and reuse packaging material. Thus, it has been concluded that 48 percent of the development cost of the cushion was decreased, 25 percent of mold modification time was significantly saved, and 27 percent of carbon dioxide (CO2) reduction was identified. The findings also aided in the development of productive packaging design, in which these design elements were beneficial to reduce environmental impact. These findings had a significant impact on the manufacturing industry in terms of the economics and time of the molded expanded polystyrene packaging development.

Fatal attraction of Caenorhabditis elegans to predatory fungi through 6-methyl-salicylic acid.

Salicylic acid is a phenolic phytohormone which controls plant growth and development. A methyl ester (MSA) derivative thereof is volatile and involved in plant-insect or plant-plant communication. Here we show that the nematode-trapping fungus Duddingtonia flagrans uses a methyl-salicylic acid isomer, 6-MSA as morphogen for spatiotemporal control of trap formation and as chemoattractant to lure Caenorhabditis elegans into fungal colonies. 6-MSA is the product of a polyketide synthase and an intermediate in the biosynthesis of arthrosporols. The polyketide synthase (ArtA), produces 6-MSA in hyphal tips, and is uncoupled from other enzymes required for the conversion of 6-MSA to arthrosporols, which are produced in older hyphae. 6-MSA and arthrosporols both block trap formation. The presence of nematodes inhibits 6-MSA and arthrosporol biosyntheses and thereby enables trap formation. 6-MSA and arthrosporols are thus morphogens with some functions similar to quorum-sensing molecules. We show that 6-MSA is important in interkingdom communication between fungi and nematodes.

Probiotic Bacillus Spores Protect Against Acetaminophen Induced Acute Liver Injury in Rats.

Acetaminophen (APAP) is one of the most used analgesics and antipyretic agents in the world. Intoxication with APAP is the main cause of acute liver toxicity in both the US and Europe. Spore-forming probiotic bacteria have the ability to resist harsh gastric and intestinal conditions. The aim of this study was to investigate the possible protective effect of Bacillus (B) species (sp) spores (B. licheniformis, B. indicus, B. subtilis, B. clausii, B. coagulans) against hepatotoxicity induced by APAP in rats. A total of 35 rats were randomly divided into seven groups: group I served as control; group II received silymarin; group III received MegaSporeBioticTM (MSB); group IV received APAP and served as the model of hepatotoxicity; group V received APAP and silymarin; group VI received APAP and MSB; group VII received APAP, silymarin and MSB. The livers for histopathological examination and blood samples were collected on the last day of the experiment. We determined aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total antioxidant capacity (TAC) levels and zonula occludens (ZO-1), tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß) expression. APAP overdose increased AST and ALT. It slowly decreased TAC compared to the control group, but pretreatment with silymarin and MSB increased TAC levels. Elevated plasma concentrations were identified for ZO-1 in groups treated with APAP overdose compared with those without APAP or receiving APAP in combination with silymarin, MSB or both. The changes were positively correlated with the levels of other proinflammatory cytokines (TNF-α, IL-1ß). In addition, histopathological hepatic injury was improved by preadministration of MSB or silymarin versus the disease model group. Bacillus sp spores had a protective effect on acute hepatic injury induced by APAP. Pretreatment with MSB resulted in a significant reduction in serum AST, ALT, TNF-α, IL-1ß, ZO-1, TAC and also hepatocyte necrosis, similar to the well-known hepatoprotective agent-silymarin.

Obtaining adequate surgical margin status in breast-conservation therapy: intraoperative ultrasound-guided resection versus specimen mammography.

BACKGROUND AND AIM: The purpose of breast-conserving surgery (BCS) for women with cancer is to perform an oncological radical procedure with disease-free margins at the final histological assessment and with the best aesthetic result possible. Intraoperative resected specimen ultrasound and intraoperative resected specimen mammography may reduce the rates of positive margins and reexcision among patients undergoing conserving therapy. Our objective is to compare the two methods with the histopathological results for a preset cut off and asses which parameters can influence the positive margin status. METHOD: A prospective study was performed on 83 patients who underwent breast conservation surgery for early breast cancer (pT1-3a pN0-1 M0) between 2014 and 2016. After excision the specimen was oriented in the operating room by the surgeon. Metallic clips and threads were placed on margins: one clip and the long thread at 12 o'clock, two clips and the short threads at 9 o'clock. The next step was intraoperative ultrasound assessment of the specimen. For the margins under 2 mm we performed selective margin shaving, followed by mammography to identify and document the lesion and finally histopathological examination of the specimen with reporting the gross and microscopic margins. The positive margins required re-excision or boost of radiation at the posterior or anterior margins, depending on the case. RESULTS: We set a cut-off at 2 mm. The sensitivity and specificity of the intraoperative margin assessment via the ultrasound method were 90.91% (95% CI 70.84-98.88%) and 67.21% (95% CI 54-78.69%) respectively. The sensitivity and specificity of the intraoperative margin assessment via the mammographic procedure were 45.45% (95% CI 24.39-67.79%) and 85.25% (95% CI 73.83-93.02%) respectively. There was positive correlation between the histopathological and intraoperative ultrasound exam (p=0.018) and negative correlation between the histopathological exam and the post-operative mammographic exam (p=0.68). We found a positive correlation between the positive margin status and age (<40), preoperative chemotherapy, intraductal carcinoma, inflammatory process around the tumor, and the immunohistochemical triple negative profile. CONCLUSIONS: According to our results, the intraoperative ultrasound of the breast specimen for a cutt-off at 2 mm can decrease the rates of margin positivity compared to the mammographic procedure and has the potential to diminish the number of subsequent undesired re-excisions.

Nitrones are able to release nitric oxide in aqueous environment under hydroxyl free radical attack.

Importance of a nitric oxide donor that can act as a spin trap might bring some new therapeutic possibilities regarding the treatment of ischemic diseases by reducing the intensity of free radical produced reperfusion lesions. These substances might be also used as a new type of photo protectors since they can absorb UV radiation, capture free radicals formed by interaction of UV radiation with tissue constituents, and tanning of the skin will be permitted due to nitric oxide release. The purpose of this work was to measure the ability of nitrones to release nitric oxide and how different factors (temperature, nitrone concentration, and free radicals) influence the releasing ability. Mostly, indirect determination of nitric oxide was carried out, by measuring nitrite and nitrate amounts (as decomposition products of nitric oxide), all nitrones proved to release significant amounts of nitric oxide. Nitrite measurements were made based on an HPLC-VIS method that uses pre-column derivatization of nitrite by forming an azo dye (limit of quantification: 5ng/ml). No good correlation was found between the amount of nitric oxide and temperature for most studied nitrones but between the formation of nitric oxide and nitrone concentration an asymptotic correlation was found. Fenton reagent also yielded formation of nitric oxide from nitrones and formed amounts were not different from those recorded for UV irradiation. Most of the nitrones effectively released about 0.5% of the maximum amount of nitric oxide that is chemically possible and estimated concentrations of 0.1µM were present in the solutions during decomposition.