IL-10 AND IL-35 AS INFLAMMATION REGULATORS IN PATIENTS WITH ALLERGIC RHINITIS AND MILD ATOPIC ASTHMA

Background. Significantly less is known about the immunoregulative cytokines, especially in allergic airway disease. This study aims to present the involvement of IL-35 and IL-10 in patients with allergic rhinitis (AR) and allergic bronchial asthma (BA). Methodology. The study comprised 71 patients –AR, patients with concomitant AR and mild atopic BA, and healthy controls (HC). We examined the serum levels of IL-35 and IL-10, along with other instrumental examinations, between March and September 2021. Findings. Levels of the regulatory cytokines IL-35 and IL-10 were significantly lower in patients than in HC (87.19±11.90 vs. 96.12±1.79 pg/ml; and 30.26±17.55 vs. 111.56±65.03 pg/ml, respectively). Furthermore, threefold higher serum IL-10 levels were found in healthy subjects compared to patients (p = 0.006). No difference in the levels of interleukins was found between the studied groups. Conclusions. Our results indicate that elevated IL-35 and IL-10 may play an essential role in reducing the activity of underlying allergic inflammation in allergic respiratory diseases, although no difference in the levels of the studied cytokines was found between the different groups of patients. Therefore, we can speculate that the immunosuppressive cytokines IL-35 and IL-10 were involved in maintaining the healthy state of no inflammation.

Hahnemann and the methodology of pathogenetic trials in healthy volunteers: a reappraisal.

This article assesses the guidelines and protocols that Hahnemann developed for homeopathic pathogenetic trials (HPTs) - often referred to as proving - and reappraise them in the light of more recent knowledge and protocols for clinical trials involving human subjects. Innovative features and methods introduced by Hahnemann and aimed at reducing bias are noted. A number of features which are now known to lead to bias in trials and which may be included in the reporting of symptoms are discussed in relation to HPTs. These features include: absence of control groups, absence of random allocation, absence of blinding, the inclusion of trivial and pre-existing symptoms, the inclusion of well-known acquaintances as trial participants, and the lack of definition of the healthy state. Advice from experts and papers published in recent decades related to the design of HPTs are discussed. The importance of developing methods to screen participants in HPTs for susceptibility to the tested medicine is discussed. The absence of trials meeting high quality standards in their design is highlighted. The article concludes with a plea for researchers to show the same desire for rigour and innovation that Hahnemann did in the development of HPTs, whilst fully recognising the requirements and protocols necessary for any trial of medicines on human beings, so that, as Hahnemann wanted, only reliable symptoms from HPTs will be admitted in the materia medica and clinical practice.

Altman Z-Score Sebagai Pengukur Potensi Kebangkrutan PT. MNC Land Sebelum Dan Selama Pandemi Covid-19

MNC Land, as one of the companies engaged in the hotel accommodation sector, has also experienced a negative impact due to the pandemic. The income statement shows a decrease in the revenue account of PT. MNC Land. If the COVID-19 pandemic lasts for a long time, it will have the potential to cause bankruptcy. Assessment of the potential bankruptcy prediction of the company can be measured through the Altman Z-Score analysis model. This study aims to assess the potential for bankruptcy of PT. MNC Land before and during the COVID-19 pandemic when measured by the Altman Z-Score model. The calculation results show that before COVID-19 spread to Indonesia (2017 – 2019) and during the pandemic (2020), PT. MNC Land Tbk is in a safe discriminant zone. The company is still in a healthy state and does not have financial problems or has no potential for bankruptcy.

Rhinoceros Serum microRNAs: Identification, Characterization, and Evaluation of Potential Iron Overload Biomarkers

Iron overload disorder (IOD) in critically endangered Sumatran (Dicerorhinus sumatrensis) and black (Diceros bicornis) rhinoceros is an over-accumulation of iron in organs which may exacerbate other diseases and indicate metabolic disturbances. IOD in rhinos is not well understood and diagnostics and therapeutics are limited in effectiveness. MicroRNAs (miRNAs) are small non-coding RNAs capable of altering protein synthesis. miRNA expression responds to physiological states and could serve as the basis for development of diagnostics and therapeutics. This study aimed to identify miRNAs differentially expressed among healthy rhinos and those afflicted with IOD or other diseases (“unhealthy”), and assess expression of select miRNAs to evaluate their potential as biomarkers of IOD. miRNAs in serum of black (n = 11 samples; five individuals) and Sumatran (n = 7 samples; four individuals) rhinos, representing individuals categorized as healthy (n = 9), unhealthy (n = 5), and afflicted by IOD (n = 3) were sequenced. In total, 715 miRNAs were identified, of which 160 were novel, 131 were specific to black rhinos, and 108 were specific to Sumatran rhinos. Additionally, 95 miRNAs were specific to healthy individuals, 31 specific to unhealthy, and 63 were specific to IOD individuals. Among healthy, unhealthy, and IOD states, 21 miRNAs were differentially expressed (P ≤ 0.01). Five known miRNAs (let-7g, miR-16b, miR-30e, miR-143, and miR-146a) were selected for further assessment via RT-qPCR in serum from black (n = 61 samples; seven individuals) and Sumatran (n = 38 samples; five individuals) rhinos. let-7g, miR-30e, and miR-143 all showed significant increased expression (P ≤ 0.05) during IOD (between 1 and 2 years prior to death) and late IOD (within 1 year of death) compared to healthy and unhealthy individuals. miR-16b expression increased (P ≤ 0.05) in late IOD, but was not different among IOD, healthy, and unhealthy states (P > 0.05). Expression of miR-146a increased in IOD and late IOD as compared to unhealthy samples (P ≤ 0.05) but was not different from the healthy state (P > 0.05). Selected serum miRNAs of black and Sumatran rhinos, in particular let-7g, miR-30e, and miR-143, could therefore provide a tool for advancing rhino IOD diagnostics that should be further investigated.

AN ATTEMPT TO UNDERSTAND THE CLINICAL APPROACH OF ADRAVYABHUTA CHIKITSA

Chikitsa (Treatment protocols) is Pravrutti (effort) made by Gunayukta Chikitsa Chatuspada (Physician, nurse, medications and patient) to bring back Dhatu Samyata (Healthy state) whenever there is Dhatu Vaikruti (Disease state). In Ayurvedic text, we got an explanation of many types of Chikitsa for different Vyadhis (Disease) or in different Avastha (Stages) of the Vyadhi. Among all these Chikitsa, we use Dravyabhuta Chikitsa (Dimensional things) like all medication including shodhana (Purification) and shamana (Pacification) broadly but the use of the Adravyabhuta Chikitsa (Non-dimensional) is very limited. Adravyabhuta is a type of Chikitsa that is classified based on the swarupa (Shape), these Adravyabhutas Chikitsa specially deals with non - dimensional things. This review article is explaining about concept and types of Adravyabhuta Chikitsa with classical examples which our Acharyas explained in Samhitas. Keywords: Chikitsa, Dravyabhuta, Adravyabhuta, Murta Bhava, Amurtha Bhava, Samavayi Karana.

Extracellular Vesicle Associated miRNAs Regulate Signaling Pathways Involved in COVID-19 Pneumonia and the Progression to Severe Acute Respiratory Corona Virus-2 Syndrome

BackgroundExtracellular vesicles (EVs) are mediators of cell-to-cell communication in inflammatory lung diseases. They function as carriers for miRNAs which regulate mRNA transcripts and signaling pathways after uptake into recipient cells. We investigated whether miRNAs associated with circulating EVs regulate immunologic processes in COVID-19.MethodsWe prospectively studied 20 symptomatic patients with COVID-19 pneumonia, 20 mechanically ventilated patients with severe COVID-19 (severe acute respiratory corona virus-2 syndrome, ARDS) and 20 healthy controls. EVs were isolated by precipitation, total RNA was extracted, profiled by small RNA sequencing and evaluated by differential gene expression analysis (DGE). Differentially regulated miRNAs between groups were bioinformatically analyzed, mRNA target transcripts identified and signaling networks constructed, thereby comparing COVID-19 pneumonia to the healthy state and pneumonia to severe COVID-19 ARDS.ResultsDGE revealed 43 significantly and differentially expressed miRNAs (25 downregulated) in COVID-19 pneumonia when compared to controls, and 20 miRNAs (15 downregulated) in COVID-19 ARDS patients in comparison to those with COVID-19 pneumonia. Network analysis for comparison of COVID-19 pneumonia to healthy controls showed upregulated miR-3168 (log2FC=2.28, padjusted<0.001), among others, targeting interleukin-6 (IL6) (25.1, 15.2 - 88.2 pg/ml in COVID-19 pneumonia) and OR52N2, an olfactory smell receptor in the nasal epithelium. In contrast, miR-3168 was significantly downregulated in COVID-19 ARDS (log2FC=-2.13, padjusted=0.003) and targeted interleukin-8 (CXCL8) in a completely activated network. Toll-like receptor 4 (TLR4) was inhibited in COVID-19 pneumonia by miR-146a-5p and upregulated in ARDS by let-7e-5p.ConclusionEV-derived miRNAs might have important regulative functions in the pathophysiology of COVID-19: CXCL8 regulates neutrophil recruitment into the lung causing epithelial damage whereas activated TLR4, to which SARS-CoV-2 spike protein binds strongly, increases cell surface ACE2 expression and destroys type II alveolar cells that secrete pulmonary surfactants; both resulting in pulmonary-capillary leakage and ARDS. These miRNAs may serve as biomarkers or as possible therapeutic targets.

Changes in Gut Bacterial Translation Occur before Symptom Onset and Dysbiosis in Dextran Sodium Sulfate-Induced Murine Colitis

Most studies on the gut microbiome focus on the composition of this community and how it changes during disease. However, how the community transitions from a healthy state to one associated with disease is currently unknown.

EUTHANASIA AND ISLAMIC RULINGS PERTINENT TO MAINTAINING AND REMOVING ARTIFICIAL LIFE SUPPORT DEVICES

This paper is intended to elaborate on the legal ruling of removing life support from a brain-dead person. Brain death means the permanent absence of brainstem and cerebral functions, not only the death of the brain cortex. Life support devices restore the functions of the heart and respiratory system, which sometimes result in the full recovery of consciousness of the patient and all of his basic functions. It is possible for the patient to restore normal breathing and leave the hospital in a full healthy state. On this basis, it is not permissible for a doctor to remove these devices before the brainstem dies, otherwise this would cause a real and irreversible death of the patient. In this case, the doctor bears full civil and criminal responsibility. The doctor is held accountable if he refrains from providing assistance to this patient who is legally and medically alive. It is permissible to remove artificial life devices once the death of the brain is ascertained in the light of the above-mentioned diagnoses. Then, the patient will be transferred to another room, but his death is announced only after the heart stops functioning. It is from this moment that the rulings of death are applied. The responsibility of removing these devices and declaring death is the work of a specialized medical committee that approves the diagnosis and issues a burial permit.

Single-cell transcriptional profiling of splenic fibroblasts reveals subset-specific innate immune signatures in homeostasis and during viral infection

Our understanding of the composition and functions of splenic stromal cells remains incomplete. Here, based on analysis of over 20,000 single cell transcriptomes of splenic fibroblasts, we characterized the phenotypic and functional heterogeneity of these cells in healthy state and during virus infection. We describe eleven transcriptionally distinct fibroblastic cell clusters, reassuring known subsets and revealing yet unascertained heterogeneity amongst fibroblasts occupying diverse splenic niches. We further identify striking differences in innate immune signatures of distinct stromal compartments in vivo. Compared to other fibroblasts and to endothelial cells, Ly6C+ fibroblasts of the red pulp were selectively endowed with enhanced interferon-stimulated gene expression in homeostasis, upon systemic interferon stimulation and during virus infection in vivo. Collectively, we provide an updated map of fibroblastic cell diversity in the spleen that suggests a specialized innate immune function for splenic red pulp fibroblasts.

A wearable microwave instrument can detect and monitor traumatic abdominal injuries in a porcine model

Abdominal injury is a frequent cause of death for trauma patients, and early recognition is essential to limit fatalities. There is a need for a wearable sensor system for prehospital settings that can detect and monitor bleeding in the abdomen (hemoperitoneum). This study evaluates the potential for microwave technology to fill that gap. A simple prototype of a wearable microwave sensor was constructed using eight antennas. A realistic porcine model of hemoperitoneum was developed using anesthetized pigs. Ten animals were measured at healthy state and at two sizes of bleeding. Statistical tests and a machine learning method were used to evaluate blood detection sensitivity. All subjects presented similar changes due to accumulation of blood, which dampened the microwave signal ($$p < 0.05$$ p < 0.05 ). The machine learning analysis yielded an area under the receiver operating characteristic (ROC) curve (AUC) of 0.93, showing 100% sensitivity at 90% specificity. Large inter-individual variability of the healthy state signal complicated differentiation of bleedings from healthy state. A wearable microwave instrument has potential for accurate detection and monitoring of hemoperitoneum, with automated analysis making the instrument easy-to-use. Future hardware development is necessary to suppress measurement system variability and enable detection of smaller bleedings.