Fibrosis in Chronic Kidney Disease: Pathophysiology and Therapeutic Targets.

Chronic kidney disease (CKD) is a slowly progressive condition characterized by decreased kidney function, tubular injury, oxidative stress, and inflammation. CKD is a leading global health burden that is asymptomatic in early stages but can ultimately cause kidney failure. Its etiology is complex and involves dysregulated signaling pathways that lead to fibrosis. Transforming growth factor (TGF)-ß is a central mediator in promoting transdifferentiation of polarized renal tubular epithelial cells into mesenchymal cells, resulting in irreversible kidney injury. While current therapies are limited, the search for more effective diagnostic and treatment modalities is intensive. Although biopsy with histology is the most accurate method of diagnosis and staging, imaging techniques such as diffusion-weighted magnetic resonance imaging and shear wave elastography ultrasound are less invasive ways to stage fibrosis. Current therapies such as renin-angiotensin blockers, mineralocorticoid receptor antagonists, and sodium/glucose cotransporter 2 inhibitors aim to delay progression. Newer antifibrotic agents that suppress the downstream inflammatory mediators involved in the fibrotic process are in clinical trials, and potential therapeutic targets that interfere with TGF-ß signaling are being explored. Small interfering RNAs and stem cell-based therapeutics are also being evaluated. Further research and clinical studies are necessary in order to avoid dialysis and kidney transplantation.

Beyond physical health: the role of psychosocial challenges and stigma in tackling the COVID-19 pandemic-A scoping review.

Background: The socio-cultural response to the Coronavirus Disease 2019 (COVID-19) and the level of adherence to evidence-based guidelines played a crucial role in determining the morbidity and mortality outcomes during the pandemic. This review aims to evaluate the impact of stigma and psycho-socio-cultural challenges on efforts to control the COVID-19 pandemic and to identify ways to mitigate such challenges in future pandemics. Methods: Using keywords including COVID-19, coronavirus, stigma, psychosocial challenges, and others, the authors searched seven major databases with a time limitation of July 2021, which yielded 2,038 results. Out of these, 15 papers were included in this review. Results: The findings of the review indicated that several psychosocial, socio-economic, and ethno-cultural factors are linked to the transmission and control of COVID-19. The research revealed that stigma and related psychosocial challenges and others, such as anxiety, fear, and stigma-driven social isolation, have resulted in significant mental health problems. Discussion: The review underscores the negative impact of stigma on COVID-19 patients, survivors, and the general population. Addressing stigma and psychosocial challenges is crucial to effectively manage the current pandemic and to prevent similar challenges during future public health crises.

Traumatic brain injury: Mechanisms, manifestations, and visual sequelae.

Traumatic brain injury (TBI) results when external physical forces impact the head with sufficient intensity to cause damage to the brain. TBI can be mild, moderate, or severe and may have long-term consequences including visual difficulties, cognitive deficits, headache, pain, sleep disturbances, and post-traumatic epilepsy. Disruption of the normal functioning of the brain leads to a cascade of effects with molecular and anatomical changes, persistent neuronal hyperexcitation, neuroinflammation, and neuronal loss. Destructive processes that occur at the cellular and molecular level lead to inflammation, oxidative stress, calcium dysregulation, and apoptosis. Vascular damage, ischemia and loss of blood brain barrier integrity contribute to destruction of brain tissue. This review focuses on the cellular damage incited during TBI and the frequently life-altering lasting effects of this destruction on vision, cognition, balance, and sleep. The wide range of visual complaints associated with TBI are addressed and repair processes where there is potential for intervention and neuronal preservation are highlighted.

Duplication and expression patterns of CYCLOIDEA-like genes in Campanulaceae.

BACKGROUND: CYCLOIDEA (CYC)-like transcription factors pattern floral symmetry in most angiosperms. In core eudicots, two duplications led to three clades of CYC-like genes: CYC1, CYC2, and CYC3, with orthologs of the CYC2 clade restricting expression dorsally in bilaterally symmetrical flowers. Limited data from CYC3 suggest that they also play a role in flower symmetry in some asterids. We examine the evolution of these genes in Campanulaceae, a group that contains broad transitions between radial and bilateral floral symmetry and 180° resupination (turning upside-down by twisting pedicle). RESULTS: We identify here all three paralogous CYC-like clades across Campanulaceae. Similar to other core eudicots, we show that CamCYC2 duplicated near the time of the divergence of the bilaterally symmetrical and resupinate Lobelioideae. However, in non-resupinate, bilaterally symmetrical Cyphioideae, CamCYC2 appears to have been lost and CamCYC3 duplicated, suggesting a novel genetic basis for bilateral symmetry in Cyphioideae. We additionally, utilized qRT-PCR to examine the correlation between CYC-like gene expression and shifts in flower morphology in four species of Lobelioideae. As expected, CamCYC2 gene expression was dorsoventrally restricted in bilateral symmetrical flowers. However, because Lobelioideae have resupinate flowers, both CamCYC2A and CamCYC2B are highly expressed in the finally positioned ventral petal lobes, corresponding to the adaxial side of the flower relative to meristem orientation. CONCLUSIONS: Our sequences across Campanulaceae of all three of these paralogous groups suggests that radially symmetrical Campanuloideae duplicated CYC1, Lobelioideae duplicated CYC2 and lost CYC3 early in their divergence, and that Cyphioideae lost CYC2 and duplicated CYC3. This suggests a dynamic pattern of duplication and loss of major floral patterning genes in this group and highlights the first case of a loss of CYC2 in a bilaterally symmetrical group. We illustrate here that CYC expression is conserved along the dorsoventral axis of the flower even as it turns upside-down, suggesting that at least late CYC expression is not regulated by extrinsic factors such as gravity. We additionally show that while the pattern of dorsoventral expression of each paralog remains the same, CamCYC2A is more dominant in species with shorter relative finally positioned dorsal lobes, and CamCYC2B is more dominant in species with long dorsal lobes.

Chronic Inflammatory Demyelinating Polyradiculoneuropathy During the COVID-19 Pandemic: Telemedicine Limitations and Strategies for Improvement.

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is a relapsing-remitting or progressive inflammatory neuropathy, which can present in a multitude of phenotypes. It can be a challenging condition to diagnose and requires thorough clinical evaluation and electrodiagnostic testing. With the outbreak of coronavirus disease in 2019 (COVID-19), large portions of the medical field converted to telemedicine to facilitate patient visits. We report a case of a 50-year-old female who was seen via video visit during the COVID-19 pandemic who was later diagnosed with CIDP and treated with intravenous immunoglobulins with improvement in clinical examination and electrodiagnostic testing. This case highlights the limitations of performing the neuromuscular examination via telemedicine.

Guillain-Barré Syndrome as a Complication of COVID-19.

Coronavirus disease 2019 (COVID-19) is associated with multiple neurological complications including Guillain-Barre syndrome (GBS). While there are reports of COVID-19 -related GBS cases, much remain unknown. We report two cases of GBS-associated COVID-19, which started about eight weeks after the initial COVID-19 infection. Such a long duration between infection and symptom onset of GBS is unusual for post-infectious GBS. Moreover, severely ill patients with COVID-19 may have prolonged hospital stay leading to critical illness myoneuropathy. Diagnosing superimposed GBS can be challenging in such cases. Clinical suspicion, nerve conduction studies with electromyography, and cerebrospinal fluid analysis can help in making the correct diagnosis. Both presented cases responded to intravenous immunoglobulin therapy.

The Effectiveness of Selective Serotonin Reuptake Inhibitors for Treatment of Obsessive-Compulsive Disorder in Adolescents and Children: A Systematic Review and Meta-Analysis.

Background: Obsessive-compulsive disorder (OCD) is a common behavioral disorder among adolescents and children. The selective serotonin reuptake inhibitors (SSRIs) are the first pharmacological choice for this condition due to mild adverse effect profile. Objective: This systematic review was performed to evaluate the efficacy of SSRI for OCD in adolescents and children. Methods: Search terms were entered into PubMed, PsycINFO, Scopus, CINAHL, and Google Scholar. The included studies were randomized, placebo-controlled trials of SSRIs conducted in populations of children and adolescents younger than 18 years. Change from baseline Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS), end-treatment CY-BOCS with respective SD, and response and remission rates were collected for continuous and dichotomous outcome assessment, respectively. Cochrane Rev Man software was used for meta-analyses, providing Forest plots where applicable. Results: SSRIs were superior to placebo with a small effect size. There was no additional benefit of combination treatment over cognitive behavioral therapy (CBT) alone, but CBT added substantial benefit to SSRI monotherapy. Fluoxetine and sertraline appear to be superior to fluvoxamine. Conclusion: The results of current systematic review and meta-analysis support the existing National Institute for Health and Care Excellence (NICE) guidelines for choosing CBT as first line of treatment and substituting it with SSRI, depending on patient preference. Adding CBT to current SSRI treatment is effective for non-responders and partial responders, but adding SSRI to ongoing CBT does not prove beneficial. The SSRIs have different effectiveness, and their relative efficacy remains to be investigated.

Use of Gabapentin in the Treatment of Substance Use and Psychiatric Disorders: A Systematic Review.

Objective: Gabapentin (GBP) is an anticonvulsant medication that is also used to treat restless legs syndrome (RLS) and posttherapeutic neuralgia. GBP is commonly prescribed off-label for psychiatric disorders despite the lack of strong evidence. However, there is growing evidence that GBP may be effective and clinically beneficial in both psychiatric disorders and substance use disorders. This review aimed to perform a systematic analysis of peer-reviewed published literature on the efficacy of GBP in the treatment of psychiatric disorders and substance use disorders. Methods: This review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The PubMed and Ovid MEDLINE literature databases were screened and filtered by using specific search terms and inclusion/exclusion criteria. The full texts of selected studies were subsequently retrieved and reviewed. The search terms generated 2,604 results from the databases. After excluding all duplicates, 1,088 citations were left. Thereafter, we applied inclusion and exclusion criteria; a total of 54 papers were retained for detailed review. Results: This literature review concludes that GBP appears to be effective in the treatment of various forms of anxiety disorders. It shows some effectiveness in bipolar disorder as an adjunctive therapeutic agent, while the evidence for monotherapy is inconclusive. In substance use disorders, GBP is effective for acute alcohol withdrawal syndrome (AWS) with mild to moderate severity; it reduces cravings, improves the rate of abstinence, and delays return to heavy drinking. GBP may have some therapeutic potential in the treatment of opioid addiction and cannabis dependence, but there is limited evidence to support its use. No significant benefit of GBP has been conclusively observed in the treatment of OCD, PTSD, depression, or cocaine and amphetamine abuse. Conclusion: GBP appears to be effective in some forms of anxiety disorders such as preoperative anxiety, anxiety in breast cancer survivors, and social phobia. GBP has shown to be safe and effective in the treatment of alcohol dependence. However, the literature suggests that GBP is effective as an adjunctive medication rather than a monotherapy. More clinical trials with larger patient populations are needed to support gabapentin's off-label use in psychiatric disorders and substance use disorders. It is worth noting that numerous clinical studies that are discussed in this review are open-label trials, which are inherently less rigorously analyzed. Therefore, more extensive investigations are required to examine not only the efficacy of GBP, but also its safety and tolerance.

Efficacy and Safety of Varenicline for Smoking Cessation in Schizophrenia: A Meta-Analysis.

Objective: Smoking represents a major public health problem among patients with schizophrenia. To this end, some studies have investigated the efficacy of varenicline for facilitating smoking cessation in schizophrenia patients. The present review seeks to synthesize the results of these studies as well as document the reported side effects of using this medication. Methods: An electronic search was performed using five major databases: PubMed, Scopus, EMBASE, Web of Science, and Cochrane Library. Included in the current analysis were randomized clinical trials (RCTs) that have investigated the effect of varenicline in promoting smoking cessation in patients with schizophrenia. Risk of bias among included RCTs was assessed using the Cochrane Collaboration's quality assessment tool. Results: Among the 828 screened articles, only four RCTs, which involved 239 participants, were eligible for meta-analysis. In patients with schizophrenia, varenicline treatment when compared to placebo significantly reduced the number of cigarettes consumed per day [SMD (95% CI) = 0.89(0.57-1.22)] and expired carbon monoxide levels [SMD (95% CI) = 0.50 (0.06-0.94)] respectively. Conclusion: Despite a limited number of studies included in the meta-analysis, our results suggest that varenicline is an effective and safe drug to assist smoking cessation in patients with schizophrenia. Future large-scale well-designed RCTs are required to validate these findings.