Pharmacological Treatment Research Articles

Effectiveness of lifestyle interventions for glycaemic control among adults with type 2 diabetes in West Africa: a systematic review and meta-analysis protocol.

Lifestyle interventions are key to the control of diabetes and the prevention of complications, especially when used with pharmacological interventions. This protocol aims to review the effectiveness of lifestyle interventions in relation to nutrition and physical activity within the West African region. This systematic review and meta-analysis seeks to understand which interventions for lifestyle modification are implemented for the control of diabetes in West Africa at the individual and community level, what evidence is available on their effectiveness in improving glycaemic control and why these interventions were effective. We will review randomised control trials and quasi-experimental designs on interventions relating to physical activity and nutrition in West Africa. Language will be restricted to English and French as these are the most widely spoken languages in the region. No other filters will be applied. Searching will involve four electronic databases - PubMed, Scopus, Africa Journals Online and Cairn.info using natural-language phrases plus reference/citation checking. Two reviewers will independently screen results according to titles and abstracts against the inclusion and exclusion criteria to identify eligible studies. Upon full-text review, all selected studies will be assessed using Cochrane's Collaboration tool for assessing the risk of bias of a study and the ROBINS-I tool before data extraction. Evidence will be synthesised narratively and statistically where appropriate. We will conduct a meta-analysis when the interventions and contexts are similar enough for pooling and compare the treatment effects of the interventions in rural to urban settings and short term to long term wherever possible. We anticipate finding a number of studies missed by previous reviews and providing evidence of the effectiveness of different nutrition and physical activity interventions within the context of West Africa. This knowledge will support practitioners and policymakers in the design of interventions that are fit for context and purpose within the West African region. This systematic review has been registered in the International Prospective Register for Systematic Reviews - PROSPERO, with registration number CRD42023435116. All amendments to this protocol during the process of the review will be explained accordingly.

Patient-clinician interactions in shared diabetes/nephrology consultations - A qualitative observation study.

The incidence of chronic disease is increasing worldwide which, in turn, increases the demand for healthcare services. To meet these demands, healthcare systems are adapting their services in order to reduce treatment costs and ensure coherence for patients with multiple diseases. One form of adaptation is shared outpatient consultations between internal medical specialties. However, little is known about how patients interact with multiple clinicians in shared consultations. This project aimed to explore how patients with diabetes and chronic kidney disease interact with multiple clinicians in a shared outpatient setting. We performed a qualitative ethnographic study, combining focused participant observations with informal field interviews. We included 17 participants, nine males and eight females with a mean age of 67.3 in the project. The data analysis was guided by Braun and Clarke's reflexive thematic analysis and Arthur Kleinman's theory of illness and disease. We found one over-arching theme: 'A consultation which encompassed both illness and disease' and four subthemes: (1) 'The medical focal point' pertained to the focus on physiological measurements in dialogue between patients and clinicians. (2) 'The possibility of negotiations' illustrated how decisions about dialysis and pharmacological treatment were based on negotiations. (3) 'Speaking different languages' displayed how patients used alternative illness-based explanations whereas clinicians tended to use biomedical language. (4) 'Perceptions of everyday life' concerned what patients considered was best for them when managing their illness and everyday lives. Patients present information on how they balance life with physiological and psychosocial challenges. When clinicians employ a biomedical perspective, opportunities to gain information on patients' illness behaviours or cues to negotiate are missed. Patients prioritise functioning on a daily level over following treatment regimes. These findings are tenuous and require verification in similar studies in similar settings. Shared Outpatient Clinic, Patient-clinician interactions.

Adenomyosis: An Update Concerning Diagnosis, Treatment, and Fertility

This review article aims to summarize current tools used in the diagnosis of adenomyosis with relative pharmacological and surgical treatment and to clarify the relative association between adenomyosis and infertility, considering the importance of an accurate diagnosis of this heterogeneous disease. Among different reported concepts, direction invagination of gland cells from the basalis endometrium deep into the myometrium is the most widely accepted opinion on the development of adenomyosis. Adenomyosis has been increasingly identified in young women with pain, AUB, infertility, or no symptoms by using imaging techniques such as transvaginal ultrasound and magnetic resonance. Furthermore, adenomyosis often coexists with other gynecological conditions, such as endometriosis and uterine fibroids, increasing the heterogeneity of available data. However, there is no agreement on the definition and classification of adenomyotic lesions from both the histopathology and the imaging points of view, and diagnosis remains difficult and unclear. A standard, universally accepted classification system needs to be implemented to improve our understanding and inform precise diagnosis of the type of adenomyosis. This could be the key to designing RCT studies and evaluating the impact of adenomyosis on quality of life in terms of menstrual symptoms, fertility, and pregnancy outcome, given the high risk of miscarriage and obstetric complications.

Role of the STING-IRF3 pathway in ambient GABA homeostasis and cognitive function.

Targeting altered expression and/or activity of GABA transporters (GATs) provide therapeutic benefit for age-related impairments, including cognitive dysfunction. However, the mechanisms underlying the transcriptional regulation of GATs are unknown. In the present study, we demonstrated that the stimulator of interferon genes (STING) upregulates GAT1 and GAT3 expression in the brain which resulted in cognitive dysfunction. Genetic and pharmacological intervention of STING suppressed the expression of both GAT1 and GAT3, increased the ambient GABA concentration, and therefore, enhanced tonic GABAA inhibition of principal hippocampal neurons, resulting in spatial learning and working memory deficits in mice in a type I interferon (IFN I)-independent manner. Stimulation of the STING-GAT pathway efficiently restored cognitive dysfunction in STING-deficient mice models. Our study uncovered for the first time that the STING signaling pathway regulates GATs expression in a cell autonomous manner and therefore could be a novel target for GABAergic cognitive deficits.Significance Statement GABA concentration in extracellular space is maintained by GABA release and clearance of GABA back to brain cells for degradation. GABA clearance from the synaptic cleft predominantly depends on level and activity of GABA transporters (GATs) in the brain. Insufficient GABA clearance resulted to an aberrant tonic GABAA inhibition in brain. In this study, we have identified an unusually high GABA content in brain of STING-deficient mice, resulting in cognitive impairment. Our results show that STING regulates GATs expression through STING-TBK1-IRF3 pathway and thus regulates GABAergic tone. This is the first study that indicates that the STING-TBK1-IRF3 signaling pathway maintains GABA homeostasis in brain, which may offer a novel therapeutic target for modulating GABAergic tone in cases of cognitive dysfunction.

The effects of Cannabis sativa and cannabinoids on the inhibition of pancreatic lipase – An enzyme involved in obesity

IntroductionObesity is a chronic noncommunicable disease characterized by excessive body fat that can have negative health consequences. Obesity is a complex disease caused by a combination of genetic, environmental, and lifestyle factors. It is characterized by a discrepancy between caloric intake and expenditure. Obesity increases the risk of acquiring major chronic diseases, including heart disease, stroke, cancer, and Type 2 diabetes mellitus (T2DM). Currently, the inhibition of pancreatic lipases (PL) is a promising pharmacological therapy for obesity and weight management. In this study, the inhibition of pancreatic lipase by Cannabis sativa (C. sativa) plant extract and cannabinoids was investigated. MethodsThe inhibitory effect was assessed using p-nitrophenyl butyrate (pNPB), and the results were obtained by calculating the percentage relative activity and assessed using one-way analysis of variance (ANOVA). Kinetic studies and spectroscopy techniques were used to evaluate the mode of inhibition. Diet-induced; and diabetic rat models were studied to evaluate the direct effects of C. sativa extract on PL activity. ResultsKinetic analyses showed that the plant extracts inhibited pancreatic lipase, with tetrahydrocannabinol (THC) and cannabinol (CBN) being the potential cause of the inhibition noted for the C. sativa plant extract. CBN and THC inhibited the pancreatic lipase activity in a competitive manner, with the lowest residual enzyme activity of 52 % observed at a 10 μg/mL concentration of CBN and 39 % inhibition at a 25 μg/mL concentration of THC. Circular dichroism (CD) spectroscopy revealed that the inhibitors caused a change in the enzyme's secondary structure. At low concentrations, THC showed potential for synergistic inhibition with orlistat. C.sativa treatment in an in vivo rat model confirmed its inhibitory effects on pancreatic lipase activity. ConclusionThe findings in this study provided insight into the use of cannabinoids as pancreatic lipase inhibitors and the possibility of using these compounds to develop new pharmacological treatments for obesity.

Examination of Excessive Mind-Wandering Following Attention-Deficit and Hyperactivity Disorder Treatment in Adults.

Although mind-wandering (MW) is a part of attention deficit and hyperactivity disorder (ADHD), the impact of psychostimulants on excessive MW remains unclear. We aimed to elucidate how psychostimulants impact the MW of adult ADHD patients post treatment. This cross-sectional cohort study consisted of 54 randomly selected ADHD patients who applied to our psychiatry outpatient clinic and 40 healthy controls. The ADHD patients were administered methylphenidate or atomoxetine. A Semi-Structured Sociodemographic and Clinical Data Form, the Adult ADHD Self-Report Scale (ASRS), and the Mind Excessively Wandering Scale (MEWS) were applied. Routine psychiatric assessments in the 1st, 2nd, and 3rd months of pharmacological treatment were carried out by a psychiatrist. The pre-treatment MEWS score of the ADHD patients was 26.09 ± 1.92, which significantly decreased to 12.78 ± 2.54 post-treatment (F = 715.250, p < .001). A statistically significant difference was identified between the mean pre-treatment ASRS total score (44.07 ± 10.09) and post-treatment score (27.34 ± 11.22; F = 50.364, p < .001). A lifetime history of alcohol/substance use was positively associated with the MEWS score. ADHD pharmacotherapy led to significant reductions in MW. Recognizing the interaction between MW and ADHD could help in the design of more specific and comprehensive interventions.

Proteinuric and Non-Proteinuric Diabetic Kidney Disease: Different Presentations of the Same Disease?

Background: Diabetic kidney disease (DKD) is a leading cause of end-stage kidney disease (ESKD) worldwide. This review examines the potential differences in clinical presentation, outcomes, and management between individuals with proteinuric DKD (P-DKD) and non-proteinuric DKD (NP-DKD). Methods: We analyzed articles published globally from 2000 and 2024. Results: Individuals with NP-DKD generally have lower blood pressure levels and a more favorable lipid profile. In contrast, histological studies show that P-DKD is associated with more severe glomerulosclerosis, mesangial expansion, arteriolar hyalinosis, interstitial-fibrosis/tubular atrophy, and immune complex deposits. Additionally, those with P-DKD are more likely to develop diabetic retinopathy and have a higher risk of all-cause mortality and progression to ESKD. Strategies to slow DKD progression, applicable to both NP-DKD and P-DKD, include non-pharmacologic and pharmacologic interventions such as renin–angiotensin system blockers, sodium-glucose co-transporter-2 inhibitors, finerenone, and glucagon-like protein receptor agonists. Conclusions: NP-DKD and P-DKD represent different presentations of the same underlying disease.

Beyond medications: a multifaceted approach to alleviating comorbid anxiety and depression in clinical settings

BackgroundComorbid anxiety and depression are common and can make the problems more complex and sometimes resistant to pharmacological treatment. In existing research, the diagnoses are often studied separately, and physical activity, healthy nutrition, psychoeducation, and social support have shown good effects. The aim of the present study was to explore the longitudinal effects of a comprehensive treatment on patients with comorbid anxiety and depression in a clinical context.MethodEighty inpatients (15 men and 65 women) in age range 23–65 years receiving psychiatric treatment in Norwegian clinic participated in the longitudinal study. Treatment was person-centered and was most frequently given for anxiety and depression, e.g., pharmacological treatment and psychotherapy, individually and in groups. In combination with this, physical activity, healthy nutrition, psychoeducation and social support in contacts with authorities and relatives were also a part of treatment. Depression and anxiety were assessed using the Beck Anxiety Inventory and Beck Depression Inventory at three points in time: baseline, at the end of treatment, and 3 months after treatment. The answers were categorized and combined into four groups according to severity of anxiety and depression to measure effects on comorbidity. Mann Whitney U test, Chi-square, Friedmans test, and McNemar test were used to analyze the data.ResultThe results showed a significant increase of frequencies in the group with mild anxiety and depression 3 months past treatment compared to baseline.ConclusionThrough the comprehensive, person-centered treatment more patients had low levels of both anxiety and depression 3 months after treatment. We suggest that clinics working with comorbid depression and anxiety patients should add physical activity, nutrition advice, social support, and psychoeducation to the traditional treatment regimes. More research concerning comorbid anxiety and depression are urgent to further expand the treatment possibilities.

Sexual health and wellbeing and the menopause: An EMAS clinical guide

IntroductionSexual health and wellbeing are significant aspects of quality of life. However, taking a sexual history is often avoided in medical practice, leaving a void in management and awareness. As the menopause can have a major impact on sexual health, it is imperative that healthcare providers are appropriately trained in sexual health and wellbeing and the aligned disciplines in order to achieve optimal care. AimTo provide an evidence-based clinical guide for the assessment and management of sexual problems at the menopause and beyond. Materials and methodsReview of the literature and consensus of expert opinion. Results and conclusionThe assessment of sexual problems includes history taking, examination and laboratory investigation (if indicated), and occasionally the use of specific validated questionnaires. Management of sexual problems requires a multidimensional approach using biopsychosocial measures. Medical management and psychosexual counselling include pharmacological and non-pharmacological interventions, and sex therapy and psychoeducation. Furthermore, perimenopausal women should be advised about the need for contraception if they wish to avoid pregnancy. Also, sexually transmitted diseases can be acquired at any age. To conclude, taking a sexual history should be incorporated into medical practice and healthcare providers should be appropriately trained to assess and manage sexual problems at the menopause and beyond.

Deciphering the physiopathology of neurodevelopmental disorders using brain organoids.

Neurodevelopmental disorders (NDD) encompass a range of conditions marked by abnormal brain development in conjunction with impaired cognitive, emotional, and behavioural functions. Transgenic animal models, mainly rodents, traditionally served as key tools for deciphering the molecular mechanisms driving NDD physiopathology, and significantly contributed to the development of pharmacological interventions aimed at treating these disorders. However, the efficacy of these treatments in humans has proven to be limited, due in part to the intrinsic constraint of animal models to recapitulate the complex development and structure of the human brain but also to the phenotypic heterogeneity found between affected individuals. Significant advancements in the field of induced pluripotent stem cells (iPSC) offer a promising avenue for overcoming these challenges. Indeed, the development of advanced differentiation protocols for generating iPSC-derived brain organoids gives the unprecedented opportunity to explore the human neurodevelopment. This review provides an overview of how 3D brain organoids have been used to investigate various NDD (i.e., Fragile X syndrome, Rett syndrome, Angelman syndrome, microlissencephaly, Prader-Willi syndrome, Timothy Syndrome, tuberous sclerosis syndrome), and elucidate their pathophysiology. We also discuss the benefits and limitations of employing such innovative 3D models compared to animal models and 2D cell culture systems, in the realm of personalized medicine.

Relationship of Non-Invasive Arterial Stiffness Parameters with 10-Year Atherosclerotic Cardiovascular Disease Risk Score in Post-COVID-19 Patients—The Results of a Cross-Sectional Study

This study evaluated the relationship of non-invasive arterial stiffness parameters with an individual 10-year risk of fatal and non-fatal atherosclerotic cardiovascular disease (ASCVD) events in the cohort post-coronavirus disease 2019 (COVID-19). The study group included 203 convalescents aged 60.0 (55.0–63.0) and 115 (56.7%) women. The ASCVD risk was assessed as low to moderate to very high based on medical history (for 62 participants with pre-existing ASCVD/diabetes/chronic kidney disease in the entire cohort) or calculated in percentages using the Systemic Coronary Risk Evaluation 2 (SCORE2) algorithm based on age, sex, smoking status, systolic blood pressure (BP), and non-high-density lipoprotein cholesterol (for 141 healthy participants). The stiffness index (SI) and reflection index (RI) measured by photoplethysmography, as well as pulse pressure (PP), calculated as the difference between systolic and diastolic BP, were markers of arterial stiffness. Stiffness parameters increased significantly with the increase in ASCVD risk in the entire cohort. In 30 (14.8%) patients in the low- to moderate-risk group, the median SI was 8.07 m/s (7.10–8.73), RI 51.40% (39.40–65.60), and PP 45.50 mmHg (40.00–57.00); in 111 (54.7%) patients in the high-risk group, the median SI was 8.70 m/s (7.40–10.03), RI 57.20% (43.65–68.40), and PP 54.00 mmHg (46.00–60.75); and in 62 (30.5%) patients in the very-high-risk group, the median was SI 9.27 m/s (7.57–10.44), RI 59.00% (50.40–72.40), and PP 60.00 mmHg (51.00–67.00). In healthy participants, the SI ≤ 9.0 m/s (sensitivity of 92.31%, area under the curve [AUC] 0.686, p &lt; 0.001) based on the receiver operating characteristics was the most sensitive variable for discriminating low to moderate risk, and PP &gt; 56.0 mmHg (sensitivity of 74.36%, AUC 0.736, p &lt; 0.001) was used for discriminating very high risk. In multivariate logistic regression, younger age, female sex, PP ≤ 50 mmHg, SI ≤ 9.0 m/s, and triglycerides &lt; 150 mg/dL had the best relationship with low to moderate SCORE2 risk. In turn, older age, currently smoking, PP &gt; 56.0 mmHg, RI &gt; 68.6%, and diastolic BP ≥ 90 mmHg were related to very high SCORE2 risk. In conclusion, arterial stiffness is significantly related to ASCVD risk in post-COVID-19 patients and can be helpful as a single risk marker in everyday practice. Cut-off points for arterial stiffness parameters determined based on SCORE2 may help make individual decisions about implementing lifestyle changes or pharmacological treatment of ASCVD risk factors

Noncanonical inheritance of phenotypic information by protein amyloids.

All known heritable phenotypic information in animals is transmitted by direct inheritance of nucleic acids, their covalent modifications or histone modifications that modulate expression of associated genomic regions. Nonetheless, numerous familial traits and disorders cannot be attributed to known heritable molecular factors. Here we identify amyloid-like protein structures that are stably inherited in wild-type animals and influence traits. Their perturbation by genetic, environmental or pharmacological treatments leads to developmental phenotypes that can be epigenetically passed onto progeny. Injection of amyloids isolated from different phenotypic backgrounds into naive animals recapitulates the associated phenotype in offspring. Genetic and proteomic analyses reveal that the 26S proteasome and its conserved regulators maintain heritable amyloids across generations, which enables proper germ cell sex differentiation. We propose that inheritance of a proteinaceous epigenetic memory coordinates developmental timing and patterning with the environment to confer adaptive fitness.

Safety and efficacy of gout treatments in people with renal impairment

Gout is common in people with chronic kidney disease and in general is sub-optimally managed. Lack of evidence due to the exclusion of people with chronic kidney disease from the majority of clinical trials, concerns about adverse effects and conflicting gout management guidelines all contribute to suboptimal management. Herein we review the evidence for the pharmacological treatment of gout, both flares and long-term urate-lowering, in people with concomitant chronic kidney disease.

When the heart and hands tell a story: an intriguing case of Holt-Oram syndrome.

Holt-Oram syndrome is a rare genetic disorder caused by a mutation in the TBX5 gene, combining skeletal and cardiac malformations. Vital prognosis depends essentially on cardiac involvement, while skeletal malformations determine functional prognosis. We describe the case of a young patient aged 49, with no particular history, who presented to the emergency department with de novo congestive heart failure. Clinical examination revealed not only signs of heart failure, but also malformations such as triphalangia of the left thumb, prono-supination defects of both forearms and dorsolumbar scoliosis. The electrocardiogram showed that an atypical atrial flutter and transthoracic echocardiography revealed an atrial septal defect. We also performed a spinal scan to assess the severity of the scoliosis. Genetic studies confirmed a TBX5 gene mutation in the patient, and family screening revealed no similar cases in the family. Management consisted mainly of pharmacological treatment of heart failure, in addition to scoliosis management. Holt-Oram syndrome is a rare genetic disorder which should be suspected in the presence of any upper limb anomaly associated with cardiac malformation and confirmed by genetic study. A family investigation is necessary after diagnosis, because of autosomal dominant inheritance.

Therapeutic efficacy of the BKCa channel opener chlorzoxazone in a mouse model of Fragile X syndrome.

Fragile X syndrome (FXS) is an X-linked neurodevelopmental disorder characterized by several behavioral abnormalities, including hyperactivity, anxiety, sensory hyper-responsiveness, and autistic-like symptoms such as social deficits. Despite considerable efforts, effective pharmacological treatments are still lacking, prompting the need for exploring the therapeutic value of existing drugs beyond their original approved use. One such repurposed drug is chlorzoxazone which is classified as a large-conductance calcium-dependent potassium (BKCa) channel opener. Reduced BKCa channel functionality has been reported in FXS patients, suggesting that molecules activating these channels could serve as promising treatments for this syndrome. Here, we sought to characterize the therapeutic potential of chlorzoxazone using the Fmr1-KO mouse model of FXS which recapitulates the main phenotypes of FXS, including BKCa channel alterations. Chlorzoxazone, administered either acutely or chronically, rescued hyperactivity and acoustic hyper-responsiveness as well as impaired social interactions exhibited by Fmr1-KO mice. Chlorzoxazone was more efficacious in alleviating these phenotypes than gaboxadol and metformin, two repurposed treatments for FXS that do not target BKCa channels. Systemic administration of chlorzoxazone modulated the neuronal activity-dependent gene c-fos in selected brain areas of Fmr1-KO mice, corrected aberrant hippocampal dendritic spines, and was able to rescue impaired BKCa currents recorded from hippocampal and cortical neurons of these mutants. Collectively, these findings provide further preclinical support for BKCa channels as a valuable therapeutic target for treating FXS and encourage the repurposing of chlorzoxazone for clinical applications in FXS and other related neurodevelopmental diseases.

Prazosin Treatment of Sleep Problems in Youth with PTSD

Post traumatic stress disorder (PTSD) is a condition characterized by reexperiencing symptoms, persistent avoidance, negative alterations in cognition and mood, and changes in arousal and reactivity in response to a traumatic event (American Psychiatric Association, 2013). The pathophysiology of PTSD is not fully understood but likely related to dysregulation of fear‐processing. Currently, the gold standard of treatment is trauma‐focused cognitive behavioral therapy (TF‐CBT). SSRIs are the only FDA‐approved pharmacologic treatments for PTSD in adults and there are no FDA approved medications to treat pediatric PTSD. Unlike studies in adults, double‐blinded randomized control trials (RCTs) did not show any efficacy for SSRIs in pediatric patients diagnosed with PTSD (Hudson et al., 2021). While estimates of pediatric PTSD prevalence varies, the prevalence of PTSD at age 18 is 7.8% (Rolling et al., 2023). Sleep disturbances such as insomnia, night‐time awakenings, and nightmares often persist despite treatment with TF‐CBT or SSRIs. Left untreated, sleep disturbances are predictive of PTSD persistence and comorbid psychiatric complications (Rolling et al., 2023). There is evidence supporting the use of the medication prazosin in alleviating pediatric PTSD sleep disturbances including nightmares and insomnia. Anywhere from 20–80% of children with PTSD report nightmares compared to a prevalence of 10–20% in the general pediatric population (Kovachy et al., 2013). There is a growing need for pharmacologic therapy given the paucity of providers trained in TF‐CBT and a need for symptomatic management. In this review, we will examine sleep disturbances in pediatric PTSD patients and discuss the feasibility of prazosin as an adjunct treatment option.

Evaluating renal injury characteristics in different rat models of hyperuricemia and elucidating pathological molecular mechanisms via serum metabolomics

Hyperuricemia has emerged as a significant global health concern, closely associated with various metabolic disorders. The adverse effects frequently observed with current pharmacological treatments for hyperuricemia highlight the urgent need for reliable animal models to elucidate the disease’s pathophysiological mechanisms, thereby facilitating the development of safer and more effective therapies. In this study, we established three rat models of hyperuricemia using potassium oxonate, either alone or in combination with fructose and adenine. Each model exhibited distinct pathological changes, with the combination of potassium oxonate, fructose, and adenine causing significantly more severe damage to liver and kidney functions than potassium oxonate alone. Serum metabolomics analyses revealed profound dysregulation in the metabolic pathways of purine, pyrimidines, and glutathione, underscoring the pivotal role of oxidative stress in the progression of hyperuricemia. We identified key biomarkers such as orotidine, ureidosuccinic acid, uracil, and pseudouridine, which are associated with uric acid-induced damage to hepatic and renal systems. MetOrigin tracing analysis further revealed that differential metabolites related to hyperuricemia are primarily involved in host-microbiome co-metabolic pathways, particularly in purine metabolism, with bacterial phyla such as Pseudomonadota, Actinomycetota, and Ascomycota being closely linked to the critical metabolic processes of uric acid production. These findings not only enhance our understanding of the pathogenic mechanisms underlying hyperuricemia but also provide a robust experimental model foundation for the development of innovative treatment strategies.

Effect of aerobic exercise program on neuropathic pain and quality of life in person with paraplegia: study protocol for a randomized controlled trial.

Individuals with spinal cord injury (SCI) often suffer from neuropathic pain which is often disabling and negatively affects function, participation, and quality of life (QoL). Pharmacological treatments lack efficacy in neuropathic pain reduction hence studying alternatives to drug treatment is necessary. Preclinical evidence of various aerobic exercises has shown positive effects on neuropathic pain but scientific studies investigating its effect in the SCI human population are limited. This study is a double-blind, parallel, two-group, randomized controlled trial with an interventional study design that aims to evaluate the effectiveness of aerobic exercise program on neuropathic pain and quality of life (QoL) in individuals with chronic paraplegia. Thirty individuals with chronic paraplegia with the neurological level of injury from T2 to L2 will be recruited from the rehabilitation department at a super specialty hospital based on the inclusion criteria. Using a 1:1 allocation ratio, the participants will be randomly assigned to one of the two groups. The intervention group will perform high-intensity interval training (HIIT) aerobic exercise using an arm ergometer based on their peak heart rate, and the control group will perform free-hand arm aerobic exercise. In both groups, the intervention will be delivered as 30-min sessions, four times a week for 6weeks. International Spinal Cord Injury Pain Basic Data Set Version 3.0 will be used for diagnosing and assessing neuropathic pain and its interference with day-to-day activities, mood, and sleep. The International Spinal Cord Society (ISCoS) QoL basic data set will be used to assess QoL, and 6-min push test distance will be used to assess peak heart rate and aerobic capacity. The effectiveness of the aerobic exercise program will be assessed based on the changes in neuropathic pain score and its interference with day-to-day activities, mood, sleep, QoL, and aerobic capacity after 3weeks mid-intervention and after 6weeks post-intervention. The trial will provide new knowledge about the effectiveness of the aerobic exercise program in improving neuropathic pain and QoL in individuals with chronic paraplegia. Clinical Trials Registry-India CTRI/2023/08/056257. Registered on 8 August 2023.

Periodic Catatonia: A Tangled Spectra within Neuropsychiatry

Catatonia was first described by Kahlbaum in 1874. Subsequently, in 1908, Kraepelin delineated a cyclical pattern of catatonia in a group of patients with Schizophrenia. Further ahead, in 1938, Gjessing demonstrated the role of nitrogen phasic change in synchronous syntonic cases of periodic catatonia. However, Stokes et al., in 1941, demonstrated it to be a result of steady accumulation rather than a phasic change in nitrogen balance. There are no reliable prevalence figures for periodic catatonia. Prominent diagnostic manuals have not given this diagnostic entity a separate nosological status, despite evidence of a discrete metabolic profile. This case series elucidates periodic catatonia in different psychiatric disorders and how a separate diagnostic criterion could help in early detection and management. We narrate three case reports of catatonic manifestations in two young adolescents and one young adult male, with no underlying medical condition. The first case report highlights intermittent brief periods of catatonic excitement beginning with acute anxiety and followed by fainting spells. The second case report narrates an acute onset manic episode which alternates with the catatonic episode. The third case report shows seasonal advents of catatonia. The pharmacological intervention itself was adequate enough to resolve the catatonic symptoms. The three cases give a purview of catatonic manifestations with differential phenomenology. The treatment of catatonia bears challenges owing to a lack of awareness and differential response to available pharmacotherapy.

Characteristics, Physiopathology and Management of Dyslipidemias in Pregnancy: A Narrative Review

Dyslipidemia is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD). During pregnancy, physiological changes elevate cholesterol and triglyceride levels to support fetal development, which can exacerbate pre-existing conditions and lead to complications such as pre-eclampsia, gestational diabetes, and increased ASCVD risk for both mother and child. Effective management strategies are necessary, especially for pregnant women with inherited forms of dyslipidemia (i.e., familial hypertriglyceridemia, hyperchylomicronemia), where personalized dietary adjustments are crucial for successful pregnancy outcomes. Pharmacological interventions and lipoprotein apheresis may be necessary for severe cases, though their use is often limited by factors such as cost, availability, and potential fetal risks. Despite the promise of advanced therapies, their widespread application remains constrained by limited studies and high costs. Thus, a personalized, multidisciplinary approach is essential for optimizing outcomes. This review provides a comprehensive overview of current strategies and evidence-based practices for managing dyslipidemia during pregnancy, emphasizing the balance of maternal and fetal health. Additionally, it discusses the physiological changes in lipid metabolism during pregnancy and their implications, particularly for women with inherited forms of dyslipidemia.