Treatment Of Disorders Research Articles

Generalized 3D registration algorithm for enhancing retinal optical coherence tomography images.

Optical coherence tomography (OCT) has emerged as the standard of care for diagnosing and monitoring the treatment of various ocular disorders due to its noninvasive nature and in vivo volumetric acquisition capability. Despite its widespread applications in ophthalmology, motion artifacts remain a challenge in OCT imaging, adversely impacting image quality. While several multivolume registration algorithms have been developed to address this issue, they are often designed to cater to one specific OCT system or acquisition protocol. We aim to generate an OCT volume free of motion artifacts using a system-agnostic registration algorithm that is independent of system specifications or protocol. We developed a B-scan registration algorithm that removes motion and corrects for both translational eye movements and rotational angle differences between volumes. Tests were carried out on various datasets obtained from two different types of custom-built OCT systems and one commercially available system to determine the reliability of the proposed algorithm. Additionally, different system specifications were used, with variations in axial resolution, lateral resolution, signal-to-noise ratio, and real-time motion tracking. The accuracy of this method has further been evaluated through mean squared error (MSE) and multiscale structural similarity index measure (MS-SSIM). The results demonstrate improvements in the overall contrast of the images, facilitating detailed visualization of retinal vasculatures in both superficial and deep vasculature plexus. Finer features of the inner and outer retina, such as photoreceptors and other pathology-specific features, are discernible after multivolume registration and averaging. Quantitative analyses affirm that increasing the number of averaged registered volumes will decrease MSE and increase MS-SSIM as compared to the reference volume. The multivolume registered data obtained from this algorithm offers significantly improved visualization of the retinal microvascular network as well as retinal morphological features. Furthermore, we have validated that the versatility of our methodology extends beyond specific OCT modalities, thereby enhancing the clinical utility of OCT for the diagnosis and monitoring of ocular pathologies.

Safety and efficacy of inebilizumab for the treatment of neuromyelitis optica spectrum disorder: end-of-study results from the open-label period of the N-MOmentum trial

Inebilizumab, an anti-CD19 B-cell-depleting antibody, demonstrated safety and efficacy in neuromyelitis optica spectrum disorder in the randomised controlled period of the N-MOmentum trial. Here, end-of-study data, including the randomised controlled period and open-label extension period, are reported. In the double-blind, randomised, placebo-controlled, phase 2/3 N-MOmentum trial, adults aged 18 years and older with an neuromyelitis optica spectrum disorder diagnosis, Expanded Disability Status Scale score of 8·0 or less, and history of either at least one acute inflammatory attack requiring rescue therapy in the past year or two attacks requiring rescue therapy in the past 2 years, were recruited from 81 outpatient specialty clinics or hospitals in 24 countries. Eligible participants were randomly assigned (3:1), using a central interactive voice system or interactive web response system, and a permuted block randomisation scheme (block size of 4), to receive intravenous inebilizumab (300 mg) or identical placebo on days 1 and 15 of the randomised period, which lasted up to 197 days. Participants and all study staff were masked to treatment assignment. The primary endpoint of the randomised period of the trial was time to onset of adjudicated neuromyelitis optica spectrum disorder attack on or before day 197. Participants in the randomised controlled period who had an adjudicated attack, completed 197 days in the study, or were in the randomised controlled period when enrolment stopped, could voluntarily enter the open-label period. In the open-label period, participants either initiated inebilizumab if assigned placebo (receiving 300 mg on days 1 and 15 of the open-label period) or continued treatment if assigned inebilizumab (receiving 300 mg on day 1 and placebo on day 15, to maintain B-cell depletion and masking of the randomised controlled period). All participants subsequently received inebilizumab 300 mg every 6 months for a minimum of 2 years. The end-of-study analysis endpoints were time to adjudicated attack and annualised attack rate (assessed in all participants who received inebilizumab at any point during the randomised controlled period or open-label period [any inebilizumab population] and the aquaporin-4 [AQP4]-IgG seropositive subgroup [any inebilizumab-AQP4-IgG seropositive population]) and safety outcomes (in all participants who were exposed to inebilizumab, analysed as-treated). This study is registered with ClinicalTrials.gov, NCT02200770, and is now complete. Between Jan 6, 2015, and Sept 24, 2018, 467 individuals were screened, 231 were randomly assigned, and 230 received at least one dose of inebilizumab (n=174) or placebo (n=56). Between May 19, 2015, and Nov 8, 2018, 165 (95%) of 174 participants in the inebilizumab group and 51 (91%) of 56 in the placebo group entered the open-label period (mean age 42·9 years [SD 12·4], 197 [91%] of 216 were female, 19 [9%] were male, 115 [53%] were White, 45 [21%] were Asian, 19 [9%] were American Indian or Alaskan Native, and 19 [9%] were Black or African American). As of data cutoff for this end of study analysis (Dec 18, 2020; median exposure 1178 days [IQR 856-1538], total exposure of 730 person-years) 225 participants formed the any inebilizumab population, and 208 (92%) participants were AQP4-IgG seropositive. Overall, 63 adjudicated neuromyelitis optica spectrum disorder attacks occurred in 47 (21%) of 225 treated participants (60 attacks occurred in 44 [21%] of 208 in the AQP4-IgG seropositive subgroup); 40 (63%) of 63 attacks occurred in 34 (15%) of 225 treated participants during the first year of treatment. Of individuals who had an adjudicated attack while receiving inebilizumab, 36 (77%) of 47 were subsequently attack-free at the end of 4 years. Annualised attack rates decreased year-on-year, with end-of-study adjusted annualised attack rates being similar in the any inebilizumab-AQP4-IgG seropositive subgroup (0·097 [95% CI 0·070-0·14]) and any inebilizumab populations (0·092 [0·067-0·13]). Overall, 208 (92%) of 225 participants who received any inebilizumab had at least one treatment-emergent adverse event, the most frequent of which were urinary tract infection (59 [26%]), nasopharyngitis (47 [21%]), and arthralgia (39 [17%]). Infection rates did not increase over 4 years. Three (1%) of 225 participants in the any inebilizumab population died during the open-label period (one each due to a CNS event of unknown cause and pneumonia, respiratory insufficiency resulting from an neuromyelitis optica spectrum disorder attack and viral pneumonia related to COVID-19), all of which were deemed to be unrelated to treatment. Data from the end-of-study analysis of the N-MOmentum trial showed continued and sustained clinical benefits of long-term inebilizumab treatment in individuals with neuromyelitis optica spectrum disorder, which supports the role of inebilizumab as a CD19+ B-cell-depleting therapy in neuromyelitis optica spectrum disorder. MedImmune and Viela Bio/Horizon Therapeutics, now part of Amgen.

MiR-26a is a Key Therapeutic Target with Enormous Potential in the Diagnosis and Prognosis of Human Disease.

MicroRNA-26a (miR-26a) belongs to small non-coding regulatory RNA molecules emerging as fundamental post-transcriptional regulators inhibiting gene expression that plays vital roles in various processes of human diseases such as depression, renal ischemia and reperfusion injury, liver injury and some refractory cancer. In this review, we expound on the results of studies about miR-26a with emphasis on its function in animal models or in vitro cell culture to simulate the most common human disease in the clinic. Furthermore, we also illustrate the underlying mechanisms of miR-26a in strengthening the antitumor activity of antineoplastic drugs. Importantly, dysregulation of miR-26a has been related to many chronic and malignant diseases, especially in neurological disorders in the brain such as depression and neurodegenerative diseases as well as cancers such as papillary thyroid carcinoma, hepatocellular carcinoma and so on. It follows that miR-26a has a strong possibility to be a potential therapeutic target for the treatment of neurological disorders and cancers. Although the research of miRNAs has made great progress in the last few decades, much is yet to be discovered, especially regarding their underlying mechanisms and roles in the complex diseases of humans. Consequently, miR-26a has been analyzed in chronic and malignant diseases, and we discuss the dysregulation of miR-26a and functional roles in the development and pathogenesis of these diseases, which is very helpful for understanding their mechanisms as new biomarkers for diagnosing and curing diseases in the near future.

A bZIP type transcription factor from Picrorhiza kurrooa modulates the expression of terpenoid biosynthesis genes in Nicotiana benthamiana

bZIP family of transcription factors are DNA-binding proteins which bind ACGT motifs in the upstream promoter region of genes. bZIP proteins play significant roles in regulation of plant growth, secondary metabolism, development, defense and response to various abiotic and biotic stresses. Up to now, there is no report on molecular and functional characterization of bZIP transcription factors in Picrorhiza kurrooa, a medicinally important endangered herb of north western Himalayan region. The species is widely used in several commercially available drug formulations like livomap, livocare and livplus for treatment of liver disorders. The medicinal properties of P. kurrooa are due to bioactive picrosides, synthesized by isoprenoid pathway. The promoters of regulatory genes viz., Pkdxs and Pkhmgr of picroside biosynthesis pathway have been reported to contain ACGT cis-acting elements (bzip motifs) at different locations. In this study, the functionality of ACGT motifs was confirmed by electrophoretic mobility shift assay (EMSA). Full length PkbZIP gene was cloned through RACE method. In silico analysis revealed PkbZIP contained a conserved signature bZIP domain (N-x7-R/K-x9-L-x6-L-x6-L). Transcriptional activation and subcellular localization assay confirmed nuclear localization of PkbZIP. EMSA with purified PkbZIP confirmed in vitro binding of PkbZIP to ACGT elements in Pkdxs and Pkhmgr promoters. The expression pattern of PkbZIP positively correlated with the picroside (active medicinal component of the plant) content in different tissues, at 15 °C and under light conditions. Transient overexpression in Nicotiana benthamiana suggested a role of PkbZIP in terpenoid biosynthesis. PkbZIP might prove as potential candidate gene to be used in genetic engineering program for enhancing the picroside content in P. kurrooa.

The Effect of a Pilot Brief Educational Intervention on Preferences Regarding Treatments for Opioid Use Disorder

PurposeNegative perceptions around medications for opioid use disorder (MOUD) amongst the public could deter patients with opioid use disorder (OUD) from engaging with MOUD. Thus, we evaluated whether a brief intervention could improve preferences for MOUD in people who may or may not use opioids. MethodsWe employed a pre-post design to assess the effect of a brief educational intervention on preferences for methadone, buprenorphine, naltrexone, and non-medication treatment in an online sample of US adults stratified by race, who may or may not use opioids. Respondents ranked their preferences in OUD treatment before and after watching four one-minute educational videos about treatment options. Changes in treatment preferences were analyzed using Bhapkar’s test and post hoc McNemar’s tests. A binary logistic generalized estimating equation (GEE) assessed factors associated with preference between treatments. ResultsThe sample had 530 responses. 194 identified as White, 173 Black, 163 Latinx. Treatment preferences changed significantly towards MOUD (p<.001). This effect was driven by changes toward buprenorphine (OR=2.38; p<.001) and away from non-medication treatment (OR=0.20; p<.001). There was no significant difference in effect by race/ethnicity. People with lower opioid familiarity were significantly more likely to change their preferences towards MOUD following the intervention. ConclusionRespondent preferences for MOUD increased following the intervention suggesting that brief educational interventions can change treatment preferences towards MOUD. These findings offer insights into perceptions of OUD treatment in a racially stratified sample and serve as a foundation for future educational materials that target MOUD preferences in the general public.

A comprehensive review on pharmacognosy, phytochemistry and pharmacological activities of 8 potent species of southeast Asia.

Genus Prunus comprising around 430 species is a vast important genus of family Rosaceae, subfamily amygdalaoidae. Among all 430 species, around 19 important species are commonly found in Indian sub-continent due to their broad nutritional and economic importance. Some most common species of genus Prunus are Prunus amygdalus, Prunus persica, Prunus armeniaca, Prunus avium, Prunus cerasus, Prunus cerasoides, Prunus domestica, Prunus mahaleb, etc. A newly introduced species of Prunus i.e Prunus sunhangii is recently discovered which is morphologically very similar to Prunus cerasoides. Plants of Prunus species are short to medium-sized deciduous trees mainly found in the northern hemisphere. In India and its subcontinent, it extends from the Himalayas to Sikkim, Meghalaya, Bhutan, Myanmar etc. Different Prunus species have been extensively studied for their morphological, microscopic, pharmacological and phytoconstituents characteristics. Total phenolic content of Prunus species explains the presence of phenols in high quantity and pharmacological activity due to phenols. Phytochemical screening of species of genus Prunus shows the presence of wide phytoconstituents which contributes in their pharmacological significance and reveals the therapeutic potential and traditional medicinal significance of this genus. Genus Prunus showed a potent antioxidant activity analyzed by 1,1-diphenyl-2-picryl-hydrazyl radical assay. Plant species belonging to the genus Prunus is widely used traditionally for the treatment of various disorders. Some specific Prunus species possess potent anticancer, anti-inflammatory, hypoglycemic etc. activity which makes the genus more interesting for further research and findings. This review is an attempt to summarize the comprehensive study of Prunus.

Biological Potential of a Bibenzyl Compound ‘Gigantol’ for the Treatment of Human Disorders: Pharmacological Activities and Analytical Aspects of an Active Phytochemical Isolated from Orchid

Background: Dendrobium chrysotoxum Lindl. is an important medicinal plant of the genus Dendrobium from the Orchidaceae family. Gigantol is one of the key bioactive phytochemicals found in Dendrobium plants. Gigantol is reported to have diverse pharmacological activities Aims: This narrative review explores the analytical aspects along with pharmacological activities of gigantol as reported in different scientific publications. Methods: To find appropriate information related to Dendrobium plants and gigantol, extensive data extraction was done using ScienceDirect, Google, PubMed, and Scopus databases, and diverse facts were collected, arranged and analyzed to know the therapeutic potential of gigantol. Analytical aspects of gigantol were also discussed in the present work. Results: Gigantol has a wide distribution in the Dendrobium officinale, Dendrobium chrysanthum, Dendrobium crystallinum, Dendrobium aphyllum, and Dendrobium devonianum. Available data indicates diverse pharmacological activities of gigantol. Preclinical studies have shown its effectiveness in the treatment of cataractogenesis, liver injury, leishmaniasis, nephrotoxicity, spasm, and skin disorders. Gigantol has been found to control hepatocellular cancer, lung cancer, breast cancer, bladder cancer, and cervical cancer. The neuroprotective, antinociceptive, anti-inflammatory, antioxidant, vasorelaxant, immune modulatory effect, antimalarial, and anti-herpetic properties of gigantol have also been observed. Applications of different analytical techniques for the isolation and characterization of gigantol were also discussed in detail. Conclusion: Gigantol has significant and diverse pharmacological activities that must be explored in clinical setup to develop therapeutic leads for different diseases and health conditions.

Anisomeles indica (L.) Kuntze leaf essential oil ameliorates LPS-induced inflammation in RAW 264.7 cells: An integrated approach of network pharmacology and experimental validation

Anisomeles indica (L.) Kuntze (Lamiaceae), commonly called catmint, is an essential oil-bearing herb used in traditional systems of medicine against rheumatism, convulsions, inflammatory skin disorders, and epilepsy. However, the efficacy and mechanism of action of its essential oil against inflammatory conditions remain elusive. The current study aims at the chemical characterization of the essential oil of A. indica leaves (AILEO) and understanding the mechanism of its anti-inflammatory effects by an integrated approach of network pharmacology and in vitro assays. GC–MS analysis of AILEO revealed a total of 30 constituents representing 94.19 % of the total oil. The majority of the chemical groups include diterpene hydrocarbons with abietatriene (58.13 %) and abietadiene (7.18 %) as the major constituents. Out of 30 compounds, 20 passed the ADME screening and were considered as active constituents. A total of 524 compound targets, 409 anti-inflammation targets, and 88 compound-disease intersecting targets were obtained. Multi-level network analysis revealed that the pharmacological mechanisms of alleviation of inflammation by AILEO are due to its interaction with five core inflammatory targets such as PI3K, AKT1, MEK1, ERK1, and RXRA involved in the PI3K-AKT signaling pathway. AILEO did not exhibit any cytotoxic effect on RAW 264.7 cells, but it significantly inhibited nitric oxide (NO) production and reduced the levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in vitro assays. Further, AILEO enhanced the expression levels of endogenous antioxidant enzymes (CAT, SOD, GPx, and GSH) in comparison to the LPS-induced group. RT-qPCR analysis revealed that AILEO modulated the level of mRNA expression of all five core targets associated with the PI3K-AKT signaling pathway, which further supported the findings of network pharmacology. This study provides valuable insights into the intricate mechanisms by which AILEO exerts anti-inflammatory action indicating its pharmacological potential as a promising candidate for the treatment of disorders linked with inflammation.

Review of Oral Tablet

Abstract: Oral drug delivery is noninvasive, has a high rate of patient compliance, is easy to handle, and doesn't require any special sterile settings, it is the most popular method of administration. Nevertheless, a number of physical, biological, and pharmacological obstacles that certain medications must overcome in order to be absorbed into the systemic circulation reduce their therapeutic efficiency. The use of nanocarriers to deliver drugs orally has proven to be an effective solution to the aforementioned problems and is being explored as a potential replacement for oral medication administration. This chapter provides an overview of the latest developments in the use of nanocarriers for oral medication delivery in the treatment of different disorders. The chapter also describes how diverse nanocarrier designs and technologies improve therapeutic potential by overcoming physical, biological, and biochemical obstacles. it is easy to produce, has few sterility limitations, is less expensive, has flexible dosage form design, and has high patient compliance, oral drug delivery (ODD) is the most convenient and favored method of drug administration. However, low medication bioavailability—which is influenced by three crucial factors—is one of the difficulties associated with oral drug delivery. The other is solubility. Many mathematical models that predict the medication's rate of solubility and dissolution have been developed in order to achieve efficient drug absorption in vivo. Similarly, models that are noncellular and cellular determine permeability. Furthermore, the medication's behavior in the gastrointestinal tract (GIT) is influenced by physiological parameters, such as pH, microbial colonization, and enzymes, as well as intrinsic drug properties. A drug's dosage form is a method of getting it into a living organism. The medicine must be administered to the site of action at a rate and concentration that will maximize therapeutic benefit and minimize side effects in order to provide the intended result. Although the oral method is still commonly used, swallowing tablets and capsules can be a regular problem. As a result, numerous studies on cutting-edge drug delivery methods have been conducted. This review focuses on oral dispersible tablets, a novel approach to drug delivery systems that are currently more focused on formulation and set a new course that not only helped patients increase their level of therapy compliance.

CHEMICAL CONSTITUENTS, TRADITIONAL USES AND PHARMACOLOGICAL PROPERTIES OF MADHUCA LONGIFOLIA: A REVIEW

Plant extracts and their derivatives are used by almost 80% of the world's population for the treatment of various infections and disorders. The current review was based on the chemical constituents, traditional uses and pharmacological properties of Madhuca longifolia. The Madhuca longifolia (Mahua) Symmachus indica is a huge deciduous tree native to Nepal, India, and Ceylon. It is also known as the Butter nut tree and is a member of the Sapotaceae family. The height of an M. longifolia tree can reach up to 70 feet. The fruiting period of the tree begins between the ages of 8 and 15, and can last up to 60 years. When ripe, the fruits have a greenish yellow colour and are oval in shape [4]. Sugars, vitamin A, ascorbic acid, thiamine, riboflavin, Ca, P, Fe, Mg, Cu, anthocyanins, betains, salts of malic and succinic acid, and many other vitamins and minerals can be found in flowers. It is the rich source of quercetin, 3-O-lrhamnosid, stigmasterol, n-hexacosanol, n-octacosanol, carotene, myricitin, erthrodiol, 3-caproxyolcan-12-en-28-ol, 3-galactoside and Xanthophylls. It was traditionally utilized in bronchitis, diabetes, rheumatism, haemorrhage, ulcer, tonsillitis, pharyngitis, and spongy gums etc. In conclusion, Madhuca longifolia is reported to be effective as antioxidant, analgesic, anti-pyretic, anti-inflammatory, immunosuppression, anti-ulcer, anti-hyperglycaemic, anti-neoplastic and anthelmintic.

Moving towards a new era for the treatment of neuromyelitis optica spectrum disorders.

Neuromyelitis optica spectrum disorders (NMOSD) include a rare group of autoimmune conditions that primarily affect the central nervous system. They are characterized by inflammation and damage to the optic nerves, brain and spinal cord, leading to severe vision impairment, locomotor disability and sphynteric disturbances. In the majority of cases, NMOSD arises due to specific serum immunoglobulin G (IgG) autoantibodies targeting aquaporin 4 (AQP4-IgG), which is the most prevalent water-channel protein of the central nervous system. Early diagnosis and treatment are crucial to manage symptoms and prevent long-term disability in NMOSD patients. NMOSD were previously associated with a poor prognosis. However, recently, a number of randomized controlled trials have demonstrated that biological therapies acting on key elements of NMOSD pathogenesis, such as B cells, interleukin-6 (IL-6) pathway, and complement, have impressive efficacy in preventing the occurrence of clinical relapses. The approval of the initial drugs marks a revolutionary advancement in the treatment of NMOSD patients, significantly transforming therapeutic options and positively impacting their prognosis. In this review, we will provide an updated overview of the key immunopathological, clinical, laboratory, and neuroimaging aspects of NMOSD. Additionally, we will critically examine the latest advancements in NMOSD treatment approaches. Lastly, we will discuss key aspects regarding optimization of treatment strategies and their monitoring.

Anti-inflammatory peptide therapeutics and the role of sulphur containing amino acids (cysteine and methionine) in inflammation suppression: A review.

Inflammation serves as our body's immune response to combat infections, pathogens, viruses, and external stimuli. Inflammation can be classified into two types: acute inflammation and chronic inflammation. Non-steroidal anti-inflammatory medications (NSAIDs) are used to treat both acute and chronic inflammatory disorders. However, these treatments have various side effects such as reduced healing efficiency, peptic ulcers, gastrointestinal toxicities, etc. METHOD: This review assesses the potential of anti-inflammatory peptides (AIPs) derived from various natural sources, such as algae, fungi, plants, animals, and marine organisms. Focusing on peptides rich in cysteines and methionine, sulphur-containing amino acids known for their role in suppression of inflammation. Due to their varied biological activity, ability to penetrate cells, and low cytotoxicity, bioactive peptides have garnered interest as possible therapeutic agents. The utilisation of AIPs has shown great potential in the treatment of disorders associated with inflammation. AIPs can be obtained from diverse natural sources such as algae, fungi, plants, and animals. Cysteine and methionine are sulphur-containing amino acids that aid in the elimination of free radicals, hence assisting in the treatment of inflammatory diseases. This review specifically examines several sources of AIPs including peptides that contain numerous cysteines and methionine. In addition, the biological characteristics of these amino acids and advancements in peptide delivery are also discussed.

Is it now time to prepare psychiatry for a psychedelic future?

Australia has just rescheduled two drugs controlled under the United Nations Psychotropic Drug Conventions, psilocybin and MDMA, as treatments for treatment-resistant depression and post-traumatic stress disorder respectively. This feature explores the reasons for these developments, the opportunities and challenges they provide to psychiatry communities and how along with health systems these communities might respond to these developments.

Infant formulas for the treatment of functional gastrointestinal disorders: A position paper of the ESPGHAN Nutrition Committee.

Functional gastrointestinal disorders (FGID), such as infant regurgitation, infant colic, and functional constipation, are common and typically physiological phenomena during the early months of an infant's life and account for frequent consultations with pediatricians. Various infant formulas are marketed for their management and are frequently given by parents to infants before a medical consultation. However, the evidence supporting their effectiveness is limited and some have altered nutritional compositions when compared to standard formulas. Thus, these products should only be used under medical supervision and upon medical advice. Marketing and over-the-counter sales do not ensure proper medical guidance and supervision. The aim of this position paper is to review the current evidence regarding the safety and efficacy of formulas specifically formulated for addressing regurgitation, colic, and constipation, recognized as FGID. The objective is to provide guidance for clinical management based on the highest quality of available evidence. A wide search using Pubmed, MEDLINE, EMBASE and Cochrane Database of Systematic Reviews was performed including the MESH terms infant formula, colic, constipation, regurgitation, reflux, palmitate, lactase, lactose, magnesium, hydrolyzed protein, prebiotics or probiotics. 752 papers were identified and screened. Finally, 72 papers were included in the paper. In the absence of evidence, recommendations reflect the authors' combined expert opinion. Final consensus was obtained by multiple e-mail exchange and meetings of the Nutrition Committee. (1) For breastfed infants experiencing FGID such as regurgitation, colic, or constipation, transitioning from breastfeeding to commercial formulas is not recommended. (2) In general, whether an infant is breastfed or formula-fed, it's crucial to reassure parents that FGIDs are normal and typically do not necessitate treatment or change to a special formula. (3) Thickened formulas, often termed anti-reflux formulas, may be considered in specific cases of regurgitation. (4) The usage of specialized formulas for infants with colic is not advised due to a lack of clinical evidence. (5) In the case of constipation in infants, the use of formulas enriched with high β-palmitate and increased magnesium content may be considered to soften the stool. Generally, there is limited evidence supporting the use of specialized formulas for FGID. Breastfeeding should never be discontinued in favor of formula feeding.

Lyophilized rumen fluid as a ruminal fermentation modifier in high grain-fed acidotic goats.

Rumen cud transfaunation re-establishes rumen micro environment and improves fermentation in recipient animals affected with digestive disorders. Preserving rumen cud or fluid will increase its availability for the treatment of rumen fermentation disorders, without having to maintain donor animals. Rumen fluid collected from healthy goats, fed standard ration having roughage 70% and concentrate 30%, was lyophilized (prefreezing -80°C, 48h; lyophilization -45°C, 32h) using 5% glycerol as cryoprotectant. The 16 S metagenome analysis of the lyophilized rumen fluid (LRF) revealed an abundance of Prevotella (33.2%). Selenomonas ruminantium (1.87%) and Megasphaera elsdenii (0.23%) were also present. Twenty-four goats having history of high grain feeding and exhibiting clinical symptoms of rumen fermentation disorders were randomly distributed into either one of the two treatment groups viz., T1 = oral administration of LRF 31g/animal/day and T2 = oral administration of sodium bicarbonate (SB) 15g/animal/day. Post intervention LRF and SB, improved animal body condition, feed intake, fecal consistency, elevated the ruminal pH at 48h, reduced propionate and lactate at 48h, reduced total volatile fatty acids (TVFA) and ammonia nitrogen at 24h. Significant reduction in serum blood urea nitrogen (BUN) and urea levels were observed even from 24h post intervention irrespective of the treatments. LRF significantly improved acetate and decreased propionate production compared to SB. LRF at 7.5% (v/v) can thus be used to counteract ruminal fermentation disorders in goats sequel to high grain ration.

Norepinephrine Reuptake Inhibition, an Emergent Treatment for Neurogenic Orthostatic Hypotension.

The NET (norepinephrine transporter) is situated in the prejunctional plasma membrane of noradrenergic neurons. It is responsible for >90% of the norepinephrine uptake that is released in the autonomic neuroeffector junction. Inhibitors of this cell membrane transporter, known as norepinephrine reuptake inhibitors (NRIs), are commercially available for the treatment of depression and attention deficit hyperactivity disorder. These agents increase norepinephrine levels, potentiating its action in preganglionic and postganglionic adrenergic neurons, the latter through activation of α-1 adrenoreceptors. Previous studies found that patients with neurogenic orthostatic hypotension can improve standing blood pressure and reduce symptoms of neurogenic orthostatic hypotension after a single administration of the selective NRI atomoxetine. This effect was primarily observed in patients with impaired central autonomic pathways with otherwise normal postganglionic sympathetic fibers, known as multiple system atrophy. Likewise, patients with normal or high norepinephrine levels may benefit from NRIs. The long-term efficacy of NRIs for the treatment of neurogenic orthostatic hypotension-related symptoms is currently under investigation. In summary, an in-depth understanding of the pathophysiology of neurogenic orthostatic hypotension resulted in the discovery of a new therapeutic pathway targeted by NRI.

The role of exosomes in the diagnostics and treatment of immune mediated skin disoders, wounds and alopecia

Exosomes are microvesicles secreted by different cells that have the specificity and ability to transfer their cargo, including various regulatory molecules, to other cells. Exosomes cargo analysis considered to be a promising approach for diagnostics and therapeutic agents delivery into cells. Molecules derived from exosome cargo supposed to be plausible diagnostics criteria. This review provides up-to-date information on the exosomes origin and composition followed by a description of their diagnostic potential. New data summarized on the possibilities of exosomes application for the treatment of chronic immune-mediated cutaneous disorders, alopecia and cutaneous wound healing.

"They Ask Questions, But They Don't Want the Answers"-Perceptions of Clinical Communication Among Veterans Discontinuing Buprenorphine for the Treatment of Opioid Use Disorder.

Many patients with opioid use disorder (OUD) discontinue treatment prematurely, increasing their risk of opioid-related overdose and death. While patient-centered care is considered the gold standard in treating chronic illness, it may be practiced less frequently in the context of OUD care. Patient-provider communication can influence patients' care experiences, potentially having an impact on treatment retention and care decision-making. This study was conducted at the VA Portland Health Care System from March 2021 to April 2022. We conducted qualitive interviews with patients who had discontinued buprenorphine for the treatment of OUD within the past year. Coding and analysis were guided by inductive qualitative content analysis. Retrospective medical record review identified clinical and demographic characteristics of participants. Twenty patients completed an interview. Participant age ranged from 28 to 74 years (median 63 years). Ninety percent of participants were white and 90% male. Many participants expressed frustration and feelings of disempowerment in OUD care processes. Patients with a history of long-term prescribed opioid use frequently expressed stigmatizing views of OUD, and perceptions of disagreement with providers over diagnosis and care choices. Elderly patients and those with multiple comorbidities expressed confusion over significant aspects of their care, as well as difficulty navigating treatment logistics like appointment requirements and medication dose changes. Some patients reported later restarting buprenorphine in new settings, and described feeling respected and involved in care decisions as a facilitator for continuing treatment. Prioritizing patient-centered communication in OUD treatment could improve the patient experience and potentially support treatment retention. Subgroups of OUD patients, such as those with a history of long-term prescribed opioid use, elderly patients with multiple comorbidities, or those who express stigmatizing medication views, could particularly benefit from tailored communication strategies that address their individual concerns.

Impulsivity and reward and punishment sensitivity among patients admitted to a specialized inpatient eating disorder treatment program

IntroductionEating disorders (EDs) are conceptualized as disorders of under- and over-control, with impulsivity reflecting under-control. Extant research indicates that impulsivity and related factors such as reward sensitivity and punishment sensitivity may serve as trait-level transdiagnostic risk and/or maintenance factors in EDs. Findings on impulsivity and reward and punishment sensitivity by diagnosis are mixed and research on the relationship between these factors and ED symptoms, hospital course, and treatment outcomes is limited.MethodsParticipants (N = 228) were patients admitted to a specialized inpatient behavioral treatment program for EDs who agreed to participate in a longitudinal study and completed self-report measures of impulsivity, reward sensitivity, and punishment sensitivity at admission. Weight and ED symptomatology were measured at admission and discharge. Hospital course variables included length of stay and premature treatment dropout.ResultsImpulsivity was lower in individuals with anorexia nervosa (AN) restricting type compared to those with AN binge/purge type or bulimia nervosa; no other group differences were observed. Higher impulsivity was associated with greater bulimic symptoms on the Eating Disorder Inventory 2 (EDI-2) at admission. Impulsivity was not related to ED symptoms, weight outcomes, length of hospital stay, or treatment dropout at program discharge.ConclusionImpulsivity may help distinguish restrictive versus binge/purge EDs, but does not necessarily relate to discharge outcomes in an intensive inpatient ED program. Findings from this study provide novel contributions to the literature on personality traits in EDs and have important clinical implications. Results suggest that patients with higher levels of impulsivity or reward and punishment sensitivity can be expected to respond to inpatient treatment. Suggestions for future research are discussed.

First Report of Anthracnose on Wurfbainia villosa var. villosa Caused by Colletotrichum gloeosporioides in China.

Wurfbainia villosa var. villosa is a traditional Chinese herbal medicine under the family Zingiberaceae, and its ripe fruits (called Fructus Amomi) are widely used clinically for the treatment of gastrointestinal disorders (Yang et al. 2023; Chen et al. 2023). In September 2023, plants of W. villosa var. villosa exhibited anthracnose-like symptoms on leaf with a disease incidence of 35% (n = 100 investigated plants) in an approximately 90 m2 field in Guangning, China (N23°42'51.70″, E112°26'35.75″). Light yellowish-green spots (~2 mm diameter) initially appeared on the infected leaves, gradually formed sub-circular or irregular spots, then fused and expanded, resulting in wilting of the leaves. To identify the causal agent, 10 symptomatic leaves were collected and transferred to the laboratory. The symptomatic leaf samples were surface sterilized in 0.5% NaClO for 2 min, and in 70% ethanol for 30 s, then washed three times with sterile water and air-dried on sterile filter paper. The leaf tissues were placed on potato dextrose agar (PDA) medium containing 100 μg mL-1 of ampicillin (Sigma-Aldrich, St. Louis, MO) and incubated for 7 days at 28°C in darkness. Nine isolates with similar colony morphology were isolated from the 10 plated leaves. Three representative isolates (GNAF03, GNAF06, GNAF09 with approximately 3.5 cm in diameter after 3 days of incubation) appeared gray to dark brown with dense aerial hyphae at the front and gray to black colonies on the reverse of the plates. Conidia were cylindrical and measured 21.2 to 29.3 μm long × 7.1 to 9.6 μm wide (n = 50). Appressoria were formed by the tips of germ tubes or hyphae and were brown, ellipsoid, thick-walled, and smooth-margined, measuring 10.2 to 12.3 μm long × 6.4 to 8.2 μm wide (n = 50). Morphologically, the fungal isolates resembled Colletotrichum sp. (Weir et al. 2012). For molecular analysis, genomic DNA was extracted from fresh mycelia of the three isolates, and the primers ACT-512F/ACT-783R, CL1/CL2A, GDF/GDR, and ITS1/ITS4 were used to amplify partial regions of rDNA-ITS, actin (ACT), calmodulin (CAL), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) regions, respectively (Weir et al. 2012). The resulting sequences with more than 99% nucleotide identity to C. gloeosporioides were submitted to GenBank (accession numbers PP552725, PP552726, and OR827444 for ACT; PP552727, PP552728, and OR827443 for CAL; PP552729, PP552730, and OR827445 for GAPDH; PP549996, PP549999, and OR841394 for ITS). A phylogenetic tree was generated by the maximum likelihood method using the concatenated sequences of ACT, CAL, GADPH, and ITS by Polysuite software (Damm et al. 2020). Based on morphological and molecular analysis, the three isolates were characterized as C. gloeosporioides. The pathogenicity of the GNAF09 isolate was assessed on W. villosa var. villosa seedling leaves inoculated by spraying with 40 μL of conidial suspension at 106 conidia mL-1 or wounded with a sterile toothpick then inoculated with mycelial agar plugs (5 mm diameter). Control leaves were inoculated with 40 μL of sterile distilled water or agar plugs without mycelia. The inoculated plants were placed in a humid chamber at 28°C with 80% humidity and a 12 h light-dark photoperiod. Symptoms similar to those seen on naturally infected leaves were observed on all inoculated leaves after 7 days inoculation. Re-isolation was performed from 80% of the inoculated leaves and isolates were confirmed as C. gloeosporioides morphologically, confirming Koch's postulates, and by sequencing the ACT, CAL, GADPH, and ITS regions. The control groups remained asymptomatic. In previous studies, C. gloeosporioides has also caused anthracnose on Chinese medicinal plants, including Baishao (Radix paeoniae alba) (Zhang et al. 2017) and Rubia cordifolia L. (Tang et al. 2020). To our knowledge, this is the first report of C. gloeosporioides causing anthracnose on W. villosa var. villosa in China. The results of our report serve as valuable references for further research on this disease.