Circulating MicroRNAs as Biomarker for Vessel-Associated Retinal Diseases.

INTRODUCTION: Vessel-associated retinal diseases are a major cause of blindness and severe visual impairment. The identification of appropriate biomarkers is of great importance to better anticipate disease progression and establish more targeted treatment options. MicroRNAs (miRNAs) are short, single-stranded, noncoding ribonucleic acids that are involved in the posttranscriptional regulation of gene expression through hybridization with messenger RNA. The expression of certain miRNAs can be different in patients with pathological processes and can be used for the detection and differentiation of various diseases. In this study, we investigate to what extent previously in vitro identified miRNAs are present as cell-free circulating miRNAs in the serum and vitreous of human patients with and without vessel-associated retinal diseases. METHODS: Relative quantification by quantitative real-time polymerase chain reaction was used to analyze miRNA expression in patients with vessel-associated retinal diseases such as age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinal vein occlusion compared with control patients. RESULTS: In serum samples, miR-29a-3p and miR-192-5p showed increased expression in patients with neovascular AMD relative to control patients. Similarly, miR-335-5p, miR-192-5p, and miR-194-5p showed increased expression in serum from patients with proliferative DR. In vitreous samples, miR-100-5p was decreased in patients with proliferative DR. Differentially expressed miRNAs showed good diagnostic accuracy in receiver operating characteristic (ROC) and area under the ROC curve analysis. CONCLUSION: The miRNAs investigated in this study may have the potential to serve as biomarkers for vessel-associated retinal diseases. Combining multiple miRNAs may enhance the predictive power of the analysis.

On the Current Care Situation and Treatment of Ocular Mucous Membrane Pemphigoid in Germany. / Zur Versorgungssituation und konservativen Therapie des okulären vernarbenden Schleimhautpemphigoids in Deutschland.

BACKGROUND: Ocular involvement in mucous membrane pemphigoid (MMP) is relatively rare, with a prevalence of 25 cases per million population, equating to approx. 2,100 patients throughout Germany. Diagnosis can be difficult - especially in cases of isolated ocular involvement - and treatment can be complex and lengthy. Immunosuppressants or immunomodulatory drugs are often used. Due to the complexity of diagnosis and treatment, MMP patients are usually referred to specialized centers. The aim of this project was to evaluate the current care situation of patients with ocular MMP in Germany. METHODS: A paper-based survey was designed and sent to all university eye clinics and other specialized centers in Germany in April 2020. The survey asked about the existence of a specialized outpatient service, the total annual number of patients with MMP, the annual number of newly diagnosed patients, any interdisciplinary collaboration for diagnostic or therapeutic purposes, as well as the local and systemic therapy used. RESULTS: Of a total of 44 clinics, 28 (64%) responded, reporting a total average of 27 ± 42 (0 - 200) patients and 3.6 ± 2.2 (0 - 10) new cases per year. This corresponds to a total of 741 patients. Only nine (32%) of the responding clinics offer specialized MMP clinics. 93% of the centers collaborate with the local dermatology department. 79% perform serological and histological diagnostics in-house. About half of the centers (n = 16) apply a standardized treatment regime. Systemic glucocorticoids (66.7%) are most commonly used, followed by mycophenolate mofetil and dapsone (57.1%), rituximab (33.3%), azathioprine and cyclophosphamide (28.6%), as well as methotrexate (19.0%). The least frequently used treatment is intravenous immunoglobulin (14.3%). CONCLUSION: This survey of German ophthalmology departments obtained data from about one third of the estimated total cohort of all patients with MMP in Germany. These are presumed to be exclusively patients with at least one ocular involvement. The complex care of these patients is usually provided in collaboration with a dermatologist and with the use of systemic anti-inflammatory medication. Currently, an ophthalmological MMP register is being established to better record the epidemiology and care situation of this rare disease in Germany and to improve it in the long term.

Quality of life and olfactory function after suprasellar craniopharyngioma surgery-a single-center experience comparing transcranial and endoscopic endonasal approaches.

The endoscopic endonasal approach to suprasellar craniopharyngiomas has become popular as alternative to transcranial approaches. However, the literature lacks data regarding quality of life and olfactory function. The assessment of the long-term quality of life and olfactory function of all patients harboring a suprasellar craniopharyngioma who underwent surgery in our department has been done. Patient characteristics and perioperative data were gathered in a prospectively maintained database. At the last follow-up visit, the olfactory function and the quality of life (ASBQ, SNOT-22) as well as visual and pituitary function were assessed. Thirteen and 17 patients underwent surgery via a transcranial (T) and endonasal (E) route, respectively. No differences were seen in ASBQ, SNOT-22, and olfactory function between T and E, but in E were more full-time worker and less obesity. CSF leaks occurred in 15% of T and 29% of E (p = 0.43). Patients from group E had a superior visual outcome which was most pronounced in the visual field. The degree of new anterior and posterior pituitary gland deficiency after surgery and in the follow-up was lower in group E. The general and sinonasal quality of life and the olfactory function are equal in E and T. E is associated with a superior visual outcome, lower rates of diabetes insipidus, and lower rates of obesity, but has a higher risk for postoperative CSF leaks.

Exploring the origins and cleanup of mercury contamination: a comprehensive review.

Mercury is a global pollutant that poses significant risks to human health and the environment. Natural sources of mercury include volcanic eruptions, while anthropogenic sources include industrial processes, artisanal and small-scale gold mining, and fossil fuel combustion. Contamination can arise through various pathways, such as atmospheric deposition, water and soil contamination, bioaccumulation, and biomagnification in food chains. Various remediation strategies, including phytoremediation, bioremediation, chemical oxidation/reduction, and adsorption, have been developed to address mercury pollution, including physical, chemical, and biological approaches. The effectiveness of remediation techniques depends on the nature and extent of contamination and site-specific conditions. This review discusses the challenges associated with mercury pollution and remediation, including the need for effective monitoring and management strategies. Overall, this review offers a comprehensive understanding of mercury contamination and the range of remediation techniques available to mitigate its adverse impacts.

Phytolith-Occluded Carbon Sequestration Potential of Oil Palm Plantation in Tamil Nadu.

Oil palm (Elaeis guineensis) has proven to be a phytolith-occluded carbon (PhytOC)-rich species that plays a vital role in acting as a carbon sink for reducing atmospheric carbon dioxide (CO2) concentration. The present research estimated the silicon, phytolith, and PhytOC contents in four (OP4), eight (OP8), and fifteen (OP15)-year-old oil palm plantations. Qualitative analysis using a scanning electron microscope (SEM) revealed the presence of abundant globular echinate phytoliths with varied diameter (8.484-10.18 µm) in fronds, empty fruit bunches, and roots. Furthermore, a wide band (400-490 cm-1) underlined a higher relative abundance of Si-OH groups in empty fruit bunches, fronds, and roots, which emphasized the amorphous nature of silica. Quantitative analysis revealed that the phytolith (phytolith/dry biomass), PhytOC (PhytOC/phytolith), and PhytOC (PhytOC/dry biomass) contents in all oil palms differed significantly (p < 0.05) and increased with age. The PhytOC stock showed significant variation, with the trend of OP15 > OP8 > OP4. The belowground biomass of OP4 (16.43 g kg-1) and OP8 (17.13 g kg-1) had a maximum PhytOC concentration compared to the aboveground biomass, and the belowground proportion varied from 20.62 to 20.65%. The study demonstrated a positive correlation between the phytolith and PhytOC contents of oil palm; thereby, oil palm should be cultivated for enhanced long-term sequestration as a phytolith accumulator.

Kinetic and isotherm insights of Diclofenac removal by sludge derived hydrochar.

Recently, hydrothermal carbonization emerges as the most viable option for the management of solid waste with high moisture content. Sludge derived hydrochar is used as an adsorbent for emerging contaminants or micro-pollutants in the domain of sustainability. Current study demonstrates the KOH activation of hydrochar produced from paper board mill sludge and evaluates its removal potential of a Non-steroidal anti-inflammatory drug, Diclofenac from aqueous solution. The activated hydrochars exhibited porous, spherical micro-structures with higher fraction of oxygenated functional groups paving way for the efficient adsorption of Diclofenac. The effect of initial Diclofenac concentration and contact time was ascertained using adsorption kinetics and isotherms. The adsorption kinetics exhibited second-order reaction for all adsorbents indicating higher coefficient of determination (R2 > 0.9). The Diclofenac adsorption on hydrochars followed Langmuir isotherm model with the post-activated hydrochar recording a highest adsorption capacity of 37.23 mg g-1 in 40 mg L-1 initial Diclofenac concentration at 15 h equilibrium time.

[Use of artificial intelligence in screening for diabetic retinopathy at a tertiary diabetes center]. / Einsatz von künstlicher Intelligenz im Screening auf diabetische Retinopathie an einer diabetologischen Schwerpunktklinik.

BACKGROUND: In 2018, IDx-DR was approved as a method to determine the degree of diabetic retinopathy (DR) using artificial intelligence (AI) by the FDA. METHODS: We integrated IDx-DR into the consultation at a diabetology focus clinic and report the agreement between IDx-DR and fundoscopy as well as IDx-DR and ophthalmological image assessment and the influence of different camera systems. RESULTS: Adequate image quality in miosis was achieved more frequently with the Topcon camera (n = 456; NW400, Topcon Medical Systems, Oakland, NJ, USA) compared with the Zeiss camera (n = 47; Zeiss VISUCAM 500, Carl Zeiss Meditec AG, Jena, Germany). Overall, IDx-DR analysis in miosis was possible in approximately 60% of the patients. All patients in whom IDx-DR analysis in miosis was not possible could be assessed by fundoscopy with dilated pupils. Within the group of images that could be evaluated, there was agreement between IDx-DR and ophthalmic fundoscopy in approximately 55%, overestimation of severity by IDx-DR in approximately 40% and underestimation in approximately 4%. The sensitivity (specificity) for detecting severe retinopathy requiring treatment was 95.7% (89.1%) for cases with fundus images that could be evaluated and 65.2% (66.7%) when all cases were considered (including those without images in miosis which could be evaluated). The kappa coefficient of 0.334 (p < 0.001) shows sufficient agreement between IDx-DR and physician's image analysis based on the fundus photograph, considering all patients with IDx-DR analysis that could be evaluated. The comparison between IDx-DR and the physician's funduscopy under the same conditions shows a low agreement with a kappa value of 0.168 (p < 0.001). CONCLUSION: The present study shows the possibilities and limitations of AI-assisted DR screening. A major limitation is that sufficient images cannot be obtained in miosis in approximately 40% of patients. When sufficient images were available the IDx-DR and ophthalmological diagnosis matched in more than 50% of cases. Underestimation of severity by IDx-DR occurred only rarely. For integration into an ophthalmologist's practice, this system seems suitable. Without access to an ophthalmologist the high rate of insufficient images in miosis represents an important limitation.

Immunophenotyping of Circulating and Intratumoral Myeloid and T Cells in Glioblastoma Patients.

Glioblastoma is the most common and lethal primary brain malignancy that almost inevitably recurs as therapy-refractory cancer. While the success of immune checkpoint blockade (ICB) revealed the immense potential of immune-targeted therapies in several types of cancers outside the central nervous system, it failed to show objective responses in glioblastoma patients as of now. The ability of glioblastoma cells to drive multiple modes of T cell dysfunction while exhibiting low-quality neoepitopes, low-mutational load, and poor antigen priming limits anti-tumor immunity and efficacy of antigen-unspecific immunotherapies such as ICB. An in-depth understanding of the GBM immune landscape is essential to delineate and reprogram such immunosuppressive circuits during disease progression. In this view, the present study aimed to characterize the peripheral and intratumoral immune compartments of 35 glioblastoma patients compared to age- and sex-matched healthy control probands, particularly focusing on exhaustion signatures on myeloid and T cell subsets. Compared to healthy control participants, different immune signatures were already found in the peripheral circulation, partially related to the steroid medication the patients received. Intratumoral CD4+ and CD8+ TEM cells (CD62Llow/CD45ROhigh) revealed a high expression of PD1, which was also increased on intratumoral, pro-tumorigenic macrophages/microglia. Histopathological analysis further identified high PSGL-1 expression levels of the latter, which has recently been linked to increased metastasis in melanoma and colon cancer via P-selectin-mediated platelet activation. Overall, the present study comprises immunophenotyping of a patient cohort to give implications for eligible immunotherapeutic targets in neurooncology in the future.

Proper layering is important for precisely timed activation of hippocampal mossy cells.

The mammalian cortex exhibits a laminated structure that may underlie optimal synaptic connectivity and support temporally precise activation of neurons. In 'reeler' mice, the lack of the extracellular matrix protein Reelin leads to abnormal positioning of cortical neurons and disrupted layering. To address how these structural changes impact neuronal function, we combined electrophysiological and neuroanatomical techniques to investigate the synaptic activation of hippocampal mossy cells (MCs), the cell type that integrates the output of dentate gyrus granule cells (GCs). While somatodendritic domains of wild-type (WT) MCs were confined to the hilus, the somata and dendrites of reeler MCs were often found in the molecular layer, where the perforant path (PP) terminates. Most reeler MCs received aberrant monosynaptic excitatory input from the PP, whereas the disynaptic input to MCs via GCs was decreased and inhibition was increased. In contrast to the uniform disynaptic discharge of WT MCs, many reeler cells discharged with short, monosynaptic latencies, while others fired with long latencies over a broad temporal window in response to PP activation. Thus, disturbed lamination results in aberrant synaptic connectivity and altered timing of action potential generation. These results highlight the importance of a layered cortical structure for information processing.

[Schirmer's test and strip meniscometry : Comparative consideration in the diagnostics of dry eye]. / Streifenmeniskometrie und Schirmer-Test : Vergleichende Betrachtung in der Diagnostik des trockenen Auges.

BACKGROUND: As one alternative to the Schirmer test, strip meniscometry has been presented as a methodology which also seems to be suitable for quantifying a lack of tear volume. METHODS: In a randomized prospective clinical study 391 eyes from 201 subjects were assigned to 3 groups according to the severity of eye surface deficiency (group 0: 225 healthy eyes, f/m = 1.25, mean age = 50.1 ± 17.6 years; group 1: 112 eyes with mild keratoconjunctivitis sicca (KCS), f/m = 1.38, mean age = 58.7 ± 13.9 years; group 2: 54 eyes with manifest KCS, f/m = 2.375, mean age = 52.6 ± 14.1 years). Objective test parameters used were strip meniscometry, Schirmer's 1 test and the Jones-test. In order to determine the condition of the ocular surface and tear film more precisely, slit-lamp examination, the detection of lid-parallel conjunctival folds (LIPCOF) and optical coherence tomography (OCT) meniscometry were also performed. Subjective discomfort was objectified by using the Ocular Surface Disease Index questionnaire (OSDI). RESULTS: The results of strip meniscometry, Schirmer's 1 test, the Jones test and OCT meniscometry were significantly lower in KCS subjects than in healthy subjects (p < 0.001), whereas the OSDI score was significantly higher (p < 0.001). The parameters strip meniscometry, Schirmer's 1 test, the Jones test and OCT meniscometry scores correlated with each other. Sensitivity and specificity of strip meniscometry ranged from 0.79 to 0.89 and from 0.42 to 0.5. CONCLUSION: Strip meniscometry is suitable to detect a lack of tear volume. Advantageous is the rapid performance of the procedure (5 s per eye) and a good agreement with established tests (e.g. Schirmer's test). To improve the specificity, strip meniscometry must be combined with other examination methods.

Application of sludge-derived KOH-activated hydrochar in the adsorptive removal of orthophosphate.

Hydrochar, a hydrothermally carbonized product, has gained attention recently as an adsorbent, among its wide environmental applications. In this study, sludge from the paper recycling industry, having a lower pollution load, was used to produce hydrochar, followed by pre-activation and post-activation using KOH. Characterizations were performed for structural morphology (SEM and TEM), molecular functionalities (FTIR) and textural features (BET surface area). Furthermore, Response Surface Methodology (RSM) was used to optimize the adsorption parameters for the removal of orthophosphate with different hydrochars. This study aimed at a low-cost, waste-to-wealth, and negative emission technology for simultaneous solid waste management and orthophosphate removal in aqueous solution. It was predicted from the adsorption experiment that an orthophosphate dose of 100 mg L-1 at substrate pH 5.11 will result in the adsorption of 9.59 mg orthophosphate per g of post-activated hydrochar after 28.6 h, which was validated using further confirmation study.

Preparation and Characterization of Optimized Hydrochar from Paper Board Mill Sludge.

The amount of Paper Board Mill Effluent Treatment Plant Sludge (PBM-ETPS) dumped from paper mills are huge and its conversion into hydrochar for the purpose of energy has broad prospects. This study investigated the optimum conditions for the production of PBM-ETPS derived hydrochar (PBM-ETPSH) through Reponse Surface Methodology (RSM) for more surface area and pore volume with minimal hydrogen to carbon (H/C) and oxygen to carbon (O/C) ratios. The PBM-ETPSH had higher heating value (HHV) of 18.39 MJ kg-1 with fixed carbon percentage of 15.6. Our results showed a reduction in H/C (35.05%) and O/C (43.7%) ratios confirming the coalification of optimized PBM-ETPSH. Thermogravimetric investigations of blending PBM-ETPSH with coal in 1:1 ratio increased its HHV to 22.25 MJ kg-1 making it suitable as an energy alternative for paper mills.

Risk Factors for Post-operative Complications in Primary Oral Cancer Surgery-a Prospective Study.

The surgical treatment of oral cavity cancers can be influenced by post-operative complications. Identification of risk factors based on clinical characteristics may assist in therapeutic planning and thereby helps in reducing complications. Here, an attempt is made to identify the factors associated with post-operative complications (complications developing within 1 month of surgery) in patients undergoing primary oral cancer surgery. Six hundred seventy-six consecutive patients who underwent primary surgery for oral cancer from December 2007 to May 2010 were prospectively evaluated. The risk factors that predict for post-operative complications were analyzed. There was one mortality and 15% (103 patients) had post-operative complications. The complications included metabolic complications, primary site problems, donor site problems, and systemic complications. Fifteen factors were found statistically significant for the development of post-operative complications by univariate analysis. On multivariate analysis, three of the 15 factors, i.e., presence of COPD, full thickness wide excision, and increased duration of surgery were found to be independently associated with the development of post-operative complications. Presence of COPD, full thickness wide excision, and increased duration of surgery were identified as independent risk factors for post-operative complications in primary oral cancer surgery. The development of complications invariably resulted in increased hospital stay. Hence, the prompt recognition of risk factors for complications based on pre-operative clinical characteristics plus the identification of the risks associated with the surgical procedure can help in determining the appropriate therapeutic planning to prevent complications and in achieving cost effectiveness.

Ascaris lumbricoides and its almost deadly complication.

Parasitic infections are still a burden in developing countries. The lack of sanitation and hygiene measures can result in an increase in morbidity and mortality due to parasitic infections. Surgery may be needed to treat serious complications caused by some of these parasites. Ascaris lumbricoides is one of the most common parasites and although infections are usually mild, severe complications, although rare, still exist. We present a case of a patient from the Ecuadorean Amazon region with limited access to drinking water. She presented to the emergency room with abdominal pain and a mass in the abdomen. After surgery, a mass with a perforation due to Ascaris was discovered. After discharge and due to lack of follow up and self-care, she became infected again, this time making her prognosis more complex and her clinical presentation more difficult. However, after proper clinical and surgical management, patient fully recovered.

Cirugía bariátrica y evolución de COVID-19 / Bariatric surgery and evolution of COVID-19

INTRODUCTION. Obesity is recognized as a risk factor for developing severe new coronavirus disease. Bariatric surgery prior to infection could behave as a protective factor against serious infections and death. OBJECTIVE. To describe the impact of bariatric surgery on the severity and mortality of patients with obesity and new coronavirus disease; through a systematic review and meta-analysis of the specialized literature from 2020-2022. METHODOLOGY. Publications indexed in databases such as Pubmed, Tripdatabase, and Google scholar, on the impact of previous bariatric surgery on the evolution and prognosis of patients with new coronavirus disease were taken. The Newcastle-Ottawa scale was used to assess quality and risk of bias. RevMan 5.0 software was used for statistical analysis. RESULTS. Eight cohort studies were included, with a population of 137 620 adult subjects with obesity and new coronavirus disease; of these, 5638 (4.09%) had a history of bariatric surgery. In the meta-analysis, it was determined that, in subjects with obesity and new coronavirus disease, the history of bariatric surgery had a protective effect against the use of mechanical ventilation [OR: 0.68; 95% CI: 0.62-0.75] (p<0.001) and mortality [OR: 0.57; 95% CI: 0.50-0.65] (p<0.01). CONCLUSIONS. The history of bariatric surgery in subjects with obesity seems to have a protective effect against the severity defined by the use of mechanical ventilation in patients with obesity and mortality due to the new coronvirus disease; therefore, the resumption of bariatric surgical activity, at pre-pandemic levels, could represent an additional benefit for candidate subjects.

INTRODUCTION. Obesity is recognized as a risk factor for developing severe new coronavirus disease. Bariatric surgery prior to infection could behave as a protective factor against serious infections and death. OBJECTIVE. To describe the impact of bariatric surgery on the severity and mortality of patients with obesity and new coronavirus disease; through a systematic review and meta-analysis of the specialized literature from 2020-2022. METHODOLOGY. Publications indexed in databases such as Pubmed, Tripdatabase, and Google scholar, on the impact of previous bariatric surgery on the evolution and prognosis of patients with new coronavirus disease were taken. The Newcastle-Ottawa scale was used to assess quality and risk of bias. RevMan 5.0 software was used for statistical analysis. RESULTS. Eight cohort studies were included, with a population of 137 620 adult subjects with obesity and new coronavirus disease; of these, 5638 (4.09%) had a history of bariatric surgery. In the meta-analysis, it was determined that, in subjects with obesity and new coronavirus disease, the history of bariatric surgery had a protective effect against the use of mechanical ventilation [OR: 0.68; 95% CI: 0.62-0.75] (p<0.001) and mortality [OR: 0.57; 95% CI: 0.50-0.65] (p<0.01). CONCLUSIONS. The history of bariatric surgery in subjects with obesity seems to have a protective effect against the severity defined by the use of mechanical ventilation in patients with obesity and mortality due to the new coronvirus disease; therefore, the resumption of bariatric surgical activity, at pre-pandemic levels, could represent an additional benefit for candidate subjects.

Platelet activation parameters and platelet-leucocyte-conjugate formation in glioblastoma multiforme patients.

Patients with glioblastoma multiforme (GBM) suffer from an increased incidence of vascular thrombotic events. However, key influencing factors of the primary hemostasis have not been characterized in GBM patients to date. Thus, the present study determines the activation level of circulating platelets in GBM patients, in-vitro reactivity to agonist-induced platelet stimulation and the formation of circulating platelet-leucocyte conjugates as well as the plasma levels of the proinflammatory lipid mediator sphingosine-1-phosphate (S1P). The endogenous thrombin potential (ETP) was determined as global marker for hemostasis. The 21 GBM patients and 21 gender and age matched healthy individuals enrolled in this study did not differ in mean total platelet count. Basal surface expression of platelet CD63 determined by flow cytometry was significantly increased in GBM patients compared to controls as was observed for the concentration of soluble P-selectin in the plasma of GBM patients. While the ETP was not affected, the immunomodulatory lipid S1P was significantly decreased in peripheral blood in GBM. Interestingly, monocyte expression of PSGL-1 (CD162) was decreased in GBM patient blood, possibly explaining the rather decreased formation of platelet-monocyte conjugates. Our study reveals an increased CD63 expression and P-selectin expression/ secretion of circulating platelets in GBM patients. In parallel a down-modulated PSGL-1 expression in circulating monocytes and a trend towards a decreased formation of heterotypic platelet-monocyte conjugates in GBM patients was seen. Whether this and the observed decreased plasma level of the immunomodulatory S1P reflects a systemic anti-inflammatory status needs to be addressed in future studies.