Etiological Factors Research Articles

Investigation of Prevalence, Etiological Factors and Risk Factors of Urinary Tract Infection in Spinal Cord Injury Patients

Background: Urinary tract infection (UTI) is a common infection that constitutes a significant portion of all hospital infections. Objectives: Given the importance of spinal cord trauma, this study aimed to investigate the prevalence, etiological factors, and risk factors of UTI in spinal cord injury (SCI) patients. Methods: In this study, patients were examined daily. If a diagnosis of UTI was confirmed, based on laboratory results and the attending physician's opinion, they were included in the study. A researcher-made checklist was then completed by the researchers. Results: The results showed that 89 (67.4%) of the patients were male, and 101 (76.5%) were married. Additionally, 44.7% of the patients were hospitalized due to traffic accidents. The results also indicated that 30.3% of patients had hematuria, 35.5% had fever, and 12.9% had scrotal pain or turbid urine. Regarding the microorganisms identified, 55.3% of patients had Escherichia coli, 11.4% had Proteus, 9.1% had Klebsiella, and 7.6% had Candida spp. Conclusions: Given the significant prevalence of UTI in patients, necessary preventive measures should be implemented to prevent infections.

The Overlooked Floppy Eyelid Syndrome: From Diagnosis to Medical and Surgical Management.

Floppy Eyelid Syndrome (FES) is an underdiagnosed ocular condition characterized by the abnormal laxity of the upper eyelids, often leading to chronic eye irritation and redness. This review provides an in-depth examination of FES, covering its pathophysiology, clinical presentation, and diagnostic and therapeutic approaches. We discuss the potential etiological factors, including genetic predispositions and associations with ocular and systemic conditions such as obesity, obstructive sleep apnea, keratoconus, and glaucoma. Diagnostic strategies are outlined, emphasizing the importance of thorough clinical examinations and specific tests for an efficacious grading and assessment of FES. Management of FES ranges from conservative medical treatments to surgical interventions for more severe cases and should be driven by a comprehensive and multidisciplinary approach. Herein, we illustrate the practical aspects of diagnosing and managing this condition. This comprehensive review aims to enhance the recognition and treatment of FES, ultimately improving the quality of life for affected patients.

Experimental immunotherapy of association infections of the gastrointestinal tract of newborn calves using yolk melange enriched with specific Y class immunoglobulins

Mass gastrointestinal diseases of newborn calves manifested by symptoms of diarrhea are caused by various etiological factors and most often occur in the form of mixed infections. Mixed infections have a more severe diarrhea than mono-infections. The economic consequences of such infections due to the high prevalence, frequent mortality and loss of productivity during further exploitation of the animal can be significant. The most common causative agents of gastrointestinal diseases of newborn calves of viral etiology is rotavirus and coronavirus infections. Mixed (viral-bacterial) infection can lead to 100% mortality of the diseased calves. Specific vaccination of springer cows against gastrointestinal pathogens in calves, which is performed to increase the number of pathogen-specific immunoglobulins in the colostrum at calf birth, and ingestion of colostrum by the calves during the first 4 hours of life are the most important strategies to prevent severe diarrhea. But as practice shows, this is not always enough. The purpose of this work was to study the effectiveness of immunoprophylaxis of associative infections of the gastrointestinal tract of newborn calves with the use of melange prepared from chicken eggs previously immunized with the vaccine "Rotagal" (Pharmagal-BIO s.r.o., Slovakia), used for the prevention of colibacillosis, rotavirus and coronavirus infections of cattle. As a result of the study, it was established that the addition of yolk melange rich in specific immunoglobulins of Y class to the colostrum in the first hours of life of the calves has a pronounced prophylactic effect, facilitates the course of the infectious process in case of the disease, saves costs for the treatment of sick animals, increases survival rate, contributes to the acceleration of live weight gain. The use of an immunobiological preparation based on transovarial immunoglobulins has a positive effect on the indicators of nonspecific resistance of newborn calves compared to the calves with early postnatal disease and antibiotic treatment.

Navigating Complexity in Postural Orthostatic Tachycardia Syndrome.

Postural Orthostatic Tachycardia Syndrome (POTS) affects up to 1% of the US population, predominantly women, and is characterized by a complex, elusive etiology and heterogeneous phenotypes. This review delves into the intricate physiology and etiology of POTS, decoding the roles of the sinoatrial node, the autonomic nervous system, fluid dynamics, and the interplay between the immune and endocrine systems. It further examines key contributing factors such as dysautonomia, thoracic hypovolemia, autonomic neuropathies, sympathetic denervation, autoimmune responses, and associations with conditions such as small-fiber neuropathy and mast cell activation syndrome. Given the numerous mysteries surrounding POTS, we also cautiously bring attention to sinoatrial node and myocardial function, particularly in how the heart responds to stress despite exhibiting a normal cardiac phenotype at rest. The potential of genomic research in elucidating the underlying mechanisms of POTS is emphasized, suggesting this as a valuable approach that is likely to improve our understanding of the genetic underpinnings of POTS. The review introduces a tentative classification system for the etiological factors in POTS, which seeks to capture the condition's diverse aspects by categorizing various etiological factors and acknowledging co-occurring conditions. This classification, while aiming to enhance understanding and optimize treatment targets, is presented as a preliminary model needing further study and refinement. This review underscores the ongoing need for research to unravel the complexities of POTS and to develop targeted therapies that can improve patient outcomes.

Multiple sclerosis and abnormal spermatozoa: A bidirectional two-sample mendelian randomization study.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, and previous observational epidemiological studies have suggested an association between MS and male infertility; male infertility due to sperm abnormalities may result from a number of aetiological factors, such as genetics, autoimmune factors, etc., and there are currently no studies to assess whether MS is associated with sperm abnormalities in men. Therefore, we performed a Mendelian randomization (MR) analysis to assess the causal relationship between MS and abnormal spermatozoa. In this study, independent single nucleotide polymorphisms (SNPs) strongly associated with multiple sclerosis (MS) were identified by mining public genome-wide association study repositories and used as instrumental variables to explore causality. The causal effect of MS on sperm abnormalities was systematically assessed using two-sample Mendelian randomization (MR) techniques, and various analytical models such as inverse variance weighting (IVW), MR-Egger and MR-PRESSO were implemented to dissect the association. In addition, a wide range of sensitivity tests, including Cochran's Q test to detect heterogeneity, MR-Egger intercept analysis to assess bias, leave-one-out to test model robustness, and funnel plot analysis to detect potential publication bias, were implemented to ensure the robustness and reliability of the causal inference results. There was a significant causal relationship between MS and abnormal sperm (OR 1.090, 95% CI [1.017-1.168], p = 0.014); The accuracy and robustness of the results were confirmed by sensitivity analysis. Here we show that there appears to be a causal relationship between multiple sclerosis and abnormal spermatozoa. MS as a chronic disease has a higher risk of concomitant sperm abnormalities in its male patients, and reproductive and fertility issues in men with MS should receive special attention from clinicians.

Epidemiological characteristics of traumatic spinal fractures among the elderly in China

The exploration of traumatic spinal fractures (TSFs) within the senior demographic has not been thoroughly scrutinized, particularly with respect to variations across genders, age groups, seasonal periods, and causative factors. This retrospective analysis aimed to dissect differences in the prevalence and characteristics of TSFs among the elderly, factoring in gender, age, seasonal timing, and causation. A retrospective analysis was conducted on the medical and imaging records of 1,415 patients, all aged 60 years or older, who were diagnosed with TSFs from 2013 to 2019. This study categorized the data by gender, age groups (60–70, 70–80, and 80 years or older), seasons, and the cause of injuries, including road traffic crashes (RTCs), falls from low heights (LHF), falls from high heights (HHF), and injuries incurred during everyday activities and agricultural labor (DFI). Male patients exhibited notably higher incidences of RTCs, high-height falls (HHFs), outdoor incidents, comas post-injury, fractures of the lower limbs (LLFs), pelvic fractures (PFs), rib fractures (RFs), intra-thoracic injuries (ITIs), intra-abdominal injuries (IAIs), cervical fractures, and spinal cord injuries (SCIs). With advancing age, there was a marked decline in occurrences of RTCs, HHFs, outdoor incidents, RFs, craniocerebral injuries (CCIs), ITIs, cervical fractures, and SCIs, while the incidences of DFIs, indoor incidents, and thoracic and lumbar (T + L) fractures notably increased. During autumn, LLF occurrences were significantly reduced, whereas the winter season saw an increase in thoracic fractures. Spring time was associated with a higher frequency of lumbar fractures and noncontiguous spinal fractures (NSFs). Significant distinctions were observed in the age distribution, injury circumstances, associated injuries, and SCIs between high-energy impacts (RTCs and HHFs) and low-energy traumas (LHFs and DFIs). In the elderly demographic, TSFs exhibited discernible distinctions based on gender, age, seasonal variations, and etiological factors, impacting the nature and circumstances of injuries, associated traumas, complications, fracture sites, and the occurrence of SCIs.

Medicinal Plants and Bioactive Compounds with Potential Anti-inflammatory and Antidiabetic Activities: A Review

Background: Inflammation is a complex process. Persistent and uncontrolled inflammation may act as an etiologic factor for many chronic disorders like diabetes. Objective: This review aims to classify the anti-inflammatory and antidiabetic medicinal plants, their traditional uses, and their active compounds that have been tested for their anti-inflammatory and antidiabetic effects. Methods: We checked scientific publications in various electronic databases from 1981 to 2021. All the molecular structures were provided in ADC/ChemSketch. Results: We reviewed 58 species, belonging to 39 families. These species have long been used in traditional medicine to cure a variety of ailments, including, dysentery, typhoid fever, anemia, digestive and cardiac disorders, as well as diabetes and inflammation. Asteraceae represents the dominant family. The most potent anti-inflammatory and antidiabetic active compounds were reviewed including myricetin, quercetin, hesperetin, rutin, luteolin, chlorogenic acid, vanillic acid, gallic acid, ferulic acid, benzoic acid, cinnamic acid, gentisic acid, camphor, 1,8-cineol, p-cymene, limonene, linalool, thymoquinone, carvacrol, aromadendrine, α-pinene, lycopene, phytol, imperatorin, chalepin, hexadecanoic acid, linoleic acid, tellimagrandin I, and trigalloyl glucose. Conclusion: This review indicates that medicinal plants have many therapeutic dynamics against inflammation and diabetes that could be exploited for the discovery of therapeutic preparation or agent for treating the two illnesses at the same time.

The effect of astaxanthin after varicocele surgery on antioxidant status and semen quality in infertile men: A triple-blind randomized clinical trial.

Varicocele (VC) is widely recognized as a prevalent etiological factor contributing to male infertility. It has been established that the generation of reactive oxygen species (ROS) plays a significant role in the progression and development of VC. Antioxidants may regulate ROS levels in these patients. Astaxanthin (ASX) is a carotenoid compound with notable antioxidant and anti-inflammatory characteristics. The current study postulated that the administration of ASX following varicocelectomy (VCT) could potentially enhance antioxidant status and semen quality in these patients. A total of 40 infertile males with clinical VC and abnormal semen analyses were randomly assigned to take part in the current trial. For 3 months following surgery, the intervention group took ASX (6 mg/day) while the control group received a placebo. After intervention, semen parameters, antioxidant status, and pro-inflammatory cytokines were compared between the two groups. Regarding semen parameters, antioxidant treatment led to a significant improvement in total and progressive motility in the treatment group (p < 0.05). Additionally, ASX led to a considerable increase in the expression levels of NRF2, Keap1, SOD2, SOD3, and BCL2, though the enhancement in the expression level of SOD3 was not statistically significant (p > .05). However, ASX significantly decreased the BAX expression level (p < .05). Even though the level of total antioxidant capacity (TAC) of seminal fluid (SF) increased significantly in the treatment group (p < .05), the level of total oxidative stress (TOS) in SF did not differ substantially between treatment and control groups (p > .05). Based on inflammatory factors in SF, ASX led to a considerable reduction in levels of TNF-α, IL-1β, and IL-6 (p < .05). Our findings demonstrated that ASX treatment provides an important contribution to VCT outcomes by modulating antioxidant status and pro-inflammatory cytokines. Our results indicated that ASX may be beneficial as an adjuvant therapy for infertile men following VCT.

Native and prosthetic septic arthritis in a university hospital in Saudi Arabia: A retrospective study.

Septic arthritis, whether native or prosthetic, poses a significant challenge in clinical practice due to its potentially devastating consequences. Despite its clinical importance, there remains a dearth of comprehensive studies and standardized diagnostic criteria, particularly in the Kingdom of Saudi Arabia. To investigate the epidemiology, microbiological profiles, and clinical characteristics of native and prosthetic septic joints in the Saudi Arabian population. Medical records of patients diagnosed with septic arthritis between January 1, 2015, and December 31, 2022, were retrospectively reviewed. Data regarding patient demographics, clinical presentation, microbiological cultures, treatment modalities, and outcomes were analyzed. In a retrospective review of 52 cases of septic arthritis, a balanced gender distribution was observed (1:1 ratio), with the knee being the most commonly affected joint (80.8%). Methicillin-resistant Staphylococcus aureus predominated in native joints (24.2%), while Brucella spp. was more prevalent in prosthetic joints (21.1%). Joint preservation was achieved in most cases (84.6%), with no significant difference in clinical features between native and prosthetic joints. However, certain comorbidities were more common in native joint cases, including renal impairment (P = 0.002), hemodialysis (P = 0.004), heart disease (P = 0.013), and chronic liver disease (P = 0.048). At the same time, osteoarthritis was more prevalent in prosthetic joint cases (P = 0.013). Vancomycin was the most frequently used antibiotic (26.9%), and most patients received antibiotics before joint aspiration (57.7%). Surgical intervention, predominantly arthrotomy, was required in most cases (32.7%). Notably, a significant association was found between joint type and mortality (odds ratio = 0.587, P = 0.048), as well as the Charlson comorbidity index and mortality (P = 0.001). This study highlighted distinctive microbiological profiles and etiological factors in septic arthritis cases in the Saudi Arabian population.

Anterior Hyperfunction Syndrome: Literature Review and Conceptual Model.

Combined Kelly syndrome, also known as anterior hyperfunction syndrome, is a complex pathological condition of the stomatognathic system, originally established by five characteristics but primarily triggered by edentulism, specifically, the absence of the upper and posterior mandibular teeth. This condition is characterized by a series of clinical features, such as bone loss, tuberosity growth, enamel wear, periodontal damage, muscle fatigue, pain, and temporomandibular joint issues. However, these features are not unique and rather reflect an oral hyperfunction state. There is a lack of consensus on the best way to assess and diagnose this condition, which is proposed to be understood as an "oral hyperfunction state" rather than a syndrome. This study aims to conduct a literature review to analyze the available information on anterior hyperfunction syndrome in dentistry, with the goal of proposing a conceptual model of the etiological risk factors that contribute to early diagnosis and the prevention of complications. This approach has important clinical implications, as it would allow for the early identification and management of risk factors, thus improving the quality of life of patients and preventing malpractice that could compromise their oral health.

Cognitive Motor Dissociation in Disorders of Consciousness

BackgroundPatients with brain injury who are unresponsive to commands may perform cognitive tasks that are detected on functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). This phenomenon, known as cognitive motor dissociation, has not been systematically studied in a large cohort of persons with disorders of consciousness.MethodsIn this prospective cohort study conducted at six international centers, we collected clinical, behavioral, and task-based fMRI and EEG data from a convenience sample of 353 adults with disorders of consciousness. We assessed the response to commands on task-based fMRI or EEG in participants without an observable response to verbal commands (i.e., those with a behavioral diagnosis of coma, vegetative state, or minimally conscious state–minus) and in participants with an observable response to verbal commands. The presence or absence of an observable response to commands was assessed with the use of the Coma Recovery Scale–Revised (CRS-R).ResultsData from fMRI only or EEG only were available for 65% of the participants, and data from both fMRI and EEG were available for 35%. The median age of the participants was 37.9 years, the median time between brain injury and assessment with the CRS-R was 7.9 months (25% of the participants were assessed with the CRS-R within 28 days after injury), and brain trauma was an etiologic factor in 50%. We detected cognitive motor dissociation in 60 of the 241 participants (25%) without an observable response to commands, of whom 11 had been assessed with the use of fMRI only, 13 with the use of EEG only, and 36 with the use of both techniques. Cognitive motor dissociation was associated with younger age, longer time since injury, and brain trauma as an etiologic factor. In contrast, responses on task-based fMRI or EEG occurred in 43 of 112 participants (38%) with an observable response to verbal commands.ConclusionsApproximately one in four participants without an observable response to commands performed a cognitive task on fMRI or EEG as compared with one in three participants with an observable response to commands. (Funded by the James S. McDonnell Foundation and others.)

Emerging trends in early-onset gastric cancer.

The incidence of early-onset gastric cancer (EOGC) is consistently increasing, and its etiology is notably complex. This increase may be attributed to distinctive factors that differ from those associated with late-onset gastric cancer (LOGC), including genetic predispositions, dietary factors, gastric microbiota dysbiosis, and screening of high-risk cases. These factors collectively contribute to the onset of cancer. EOGC significantly differs from LOGC in terms of clinicopathological and molecular characteristics. Moreover, multiple differences in prognosis and clinical management also exist. This study aimed to systematically review the latest research advancements in the epidemiological characteristics, etiological factors, clinicopathological and molecular features, prognosis, and treatment modalities of EOGC.

The relationship between obstructive sleep apnea syndrome severity and vitamin D levels in sera

Aims: Obstructive Sleep Apnea Syndrome (OSAS) is a disorder characterized by complete or partial upper airway obstruction episodes and frequently decreased arterial oxygen saturation. Etiological factors and risk factors of OSAS are still investigated and studies in this topic continue. Until recently, researches were focused on the major effects of vitamin D on the bone metabolism and calcium homeostasis. Today; it has been found that vitamin D plays roles in many cells and tissues of human body additional to its functions in the musculoskeletal system. In our study, we aimed to examine vitamin D levels in patients who are diagnosed as OSAS and to investigate the relationship between OSAS and vitamin D deficiency. Methods: 83 volunteers, who were suspected to have OSAS, were included in the study. They all underwent polysomnography (PSG) in the Sleep Disorders Center in Pulmonary Department, between January 2015 – May 2015. Twenty cases with apnea hypopnea index (AHİ) &lt; 5/hour were evaluated as simple snoring/control group. Cases with AHİ &gt; 5/hour were diagnosed as OSAS; 22 patients were diagnosed as mild, 20 patients were diagnosed as moderate and 21 patients were diagnosed as severe OSAS. Blood samples of these patients were studied for the measurement of vitamin D [25(OH)D3], parathormone (PTH) , calcium (Ca), phosphor (P) levels and the samples were quickly delivered to biochemistry laboratory Results: A statistically significant difference in vitamin D levels were observed (p&lt;0.05) between the control and OSAS groups. However, no statistically significant difference was found in PTH, Ca, P levels among these groups (p&gt;0.05). Vitamin D levels in the control group were significantly higher than the mild and the severe OSAS patients. No statistically significant difference was observed in PTH, Ca, P levels between these patients. Conclusion: Our study indicates that there is a significant relationship between vitamin D deficiency and OSAS. This finding suggests that vitamin D deficiency may play a role in the OSAS physiopathology. There are few studies exists about the association between vitamin D deficiency and OSAS. In this regard, we think our study will contribute to the literature. Moreover; prospective, randomized, controlled studies with large series were needed.

Environmental Exposures Continue to be a Possible Etiological Factor in the Development Amyotrophic Lateral Sclerosis (ALS)

Environmental Exposures Continue to be a Possible Etiological Factor in the Development Amyotrophic Lateral Sclerosis (ALS)

Oral Health and "Modern" Digestive Diseases: Pathophysiologic and Etiologic Factors.

In the contemporary era of medicine, exploring the complexity of the human body and its intricate interactions has become a central concern for health researchers. The main purpose of this article is to summarize the current understanding of relevant pathophysiological factors such as chronic inflammation, dysbiosis (microbial imbalance), and metabolic disorders, as well as etiological factors including dietary habits, lifestyle choices, obesity, metabolic syndrome, and genetic predispositions, as well as to emphasize potential avenues for upcoming studies and their medical significance. Additionally, this article aims to assess the potential impact of integrated treatment approaches on patient outcomes, emphasizing the need for interdisciplinary collaboration between gastroenterologists, dentists, and other healthcare professionals to develop comprehensive care plans that address both oral and digestive health issues simultaneously. Among the branches with a significant impact on general well-being are oral cavity health and digestive diseases, which have been the subject of intensive research in recent decades. In this context, analysis of the current state of knowledge on oral cavity disorders in relation to "modern" digestive diseases such as non-alcoholic fatty liver disease (NAFLD), small intestinal bacterial overgrowth (SIBO), inflammatory bowel disease (IBD), and irritable bowel syndrome (IBS) becomes essential for a deeper understanding of the interconnections between oral and digestive health. The temporal overlap or succession, whether preceding or following, of oral manifestations and digestive disorders should be taken seriously by both gastroenterologists and dentists to facilitate early diagnosis and explain to patients the correlation between these two body systems. In summary, this article underscores the importance of understanding the intricate relationship between oral and digestive health, advocating for interdisciplinary approaches to improve patient outcomes and guide future research.

Estimation of relationship between serum lipids level and colorectal carcinoma: a cross-sectional study in VIMSAR, Odisha

The fourth most prevalent cancer-related cause of death worldwide is colorectal cancer. Some authors have suggested that among other risk factors, the serum lipid profile is one of the etiological risk factors. Therefore, measurement of serum lipid in this illness can establish a relationship between a healthy diet and colorectal cancer.To thoroughly research the connection between blood lipid levels and colon cancer outcomes in an effort to discover any tips for preventing this deadly condition.Patients who were hospitalised to the General Surgery department at VIMSAR, Burla between December 2020 and October 2022 were divided into two groups for the research. 40 instances of patients with colorectal cancer were randomly chosen as the case group, and 40 cases of patients with other diseases—diseases other than colorectal cancer—were chosen as the controls group. The cases were all diagnosed with carcinoma of various regions of the colon and rectum at various stages and in various age groups. Both the case and control groups' blood concentrations of TC, HDL-C, VLDL-C, LDL-C, and TG were determined for comparison and analysis.Regardless of sex, location, or stage of the malignancy, the blood levels of TC, TG, and LDL-C were lower in the tumour group than they were in the control group. On site comparison, right sided cases were much less common than left sided carcinomas, and the drop in the level of serum TC was statistically significant. However, significant differences were detected in the serum levels of the aforementioned parameters in advanced cases, which only included Dukes' C1 and C2. A negative relationship exists between serum TC, TG, and LDL-C levels and colorectal cancer. In order to design a more curative course of action for treating this dreadful illness, it may be used for follow-up treatment of colorectal carcinoma cases as well as a low level of these serum parameters preceding the disease or in early tumours. Our study only included a small number of people, thus more research and a cohort study based on the entire population are needed to fully understand this association.

Neuropeptide alpha-Melanocyte stimulating hormone preserves corneal endothelial morphology in a murine model of Fuchs dystrophy

Fuchs endothelial corneal dystrophy is a heterogenous disease with multifactorial etiology, and genetic, epigenetic, and exogenous factors contributing to its pathogenesis. DNA damage plays a significant role, with ultraviolet-A (UV-A) emerging as a key contributing factor. We investigate the potential application of neuropeptide α-melanocyte stimulating hormone (α-MSH) in mitigating oxidative stress induced endothelial damage. First, we examined the effects of α-MSH on a cultured human corneal endothelial cell line (HCEnC-21T) exposed to hydrogen peroxide (H2O2) induced oxidative DNA damage. We performed immunofluorescence and flow cytometry to assess DNA damage and cell death in the cultured cells. Additionally, we used an established mouse model that utilizes ultraviolet light to induce corneal endothelial cell damage resulting in decreased CEnC number, increased cell size variability, and decreased percentage of hexagonal cells. This endothelial decompensation leads to an increase in corneal thickness. Following UV-A exposure, the mice were systemically treated with α-MSH, either immediately after exposure (early treatment) or beginning two weeks post-exposure (delayed treatment). To evaluate treatment efficacy, we analyzed CEnC density and morphology using in vivo confocal microscopy, and central corneal thickness using anterior segment optical coherence tomography. Our findings demonstrated that α-MSH treatment effectively protects HCEnC-21T from free-radical induced oxidative DNA damage and subsequent cell death. In vivo, α-MSH treatment, mitigated the loss of CEnC density, deterioration of cell morphology and suppression of the resultant corneal swelling. These results underline the potential application of α-MSH as a therapeutic agent for mitigating corneal endothelial damage.

Long-Term Outcomes of Anticomplement Factor H Antibody Positive Versus Negative Atypical Hemolytic Uremic Syndrome

Background Atypical hemolytic uremic syndrome (aHUS) is a severe thrombotic microangiopathy predominantly affecting the kidneys, often associated with complement dysregulation. This study is aimed to analyze the clinical characteristics, treatment outcomes, and long-term implications of aHUS in a resource-limited setting. Materials and Methods A retrospective observational study conducted at an institute between January 2016 and December 2022 included all patients with aHUS, excluding secondary causes and renal transplant recipients. Demographic profiles, clinical features, laboratory parameters, treatment modalities (immunosuppression and plasma exchange), and outcomes were collected. Anticomplement Factor H (anti-CFH) antibody, complement levels, and genetic mutation analysis were performed to ascertain etiological factors. The patient and renal outcomes of anti-CFH positive and negative patients on long-term follow-up were compared. Results Fifty-seven patients (mean age: 12.5 ± 4.9 years; 63% males) were analyzed. Among them, 33 (57.9%) tested positive for anti-CFH antibodies and eight presented postpartum. Initial remission was achieved in 42 (73.6%) patients, with 13 (22.8%) partial and 29 (50.9%) complete remission. The median follow-up duration was 24 months [interquartile range (IQR) 8.5–84]; 12 (21%) patients died, with two deaths during the index admission, six among nonresponders, and 4 among responders. Dialysis-free renal survival was superior in anti-CFH seropositive patients (81.2%) compared to seronegative counterparts (55.9%), while patient survival was statistically similar between the two groups. Elevated anti-CFH titers (&gt;4000 AU/ml), age ≥16 years, female gender, and seizures predicted nonresponsiveness. Conclusion Anti-CFH antibody associated aHUS had better kidney outcomes than the seronegative counterparts. In resource limited settings, a combination of plasma exchange and immunosuppression showed promising results in the short and long term.

Precision therapy for cancer prevention by targeting carcinogenesis.

Cancer represents a major global public health burden, with new cases estimated to increase from 14 million in 2012 to 24 million by 2035. Primary prevention is an effective strategy to reduce the costs associated with cancer burden. For example, measures to ban tobacco consumption have dramatically decreased lung cancer incidence and vaccination against human papillomavirus can prevent cervical cancer development. Unfortunately, the etiological factors of many cancer types are not completely clear or are difficult to actively control; therefore, the primary prevention of such cancers is not practical. In this review, we update the progress on precision therapy by targeting the whole carcinogenesis process, especially for three high-risk groups: (1) those with chronic inflammation, (2) those with inherited germline mutations, and (3) those with precancerous lesions like polyps, gastritis, actinic keratosis or dysplasia. We believe that attenuating chronic inflammation, treating precancerous lesions, and removing high-risk tissues harboring germline mutations are precision methods for cancer prevention.

Macular structural integrity estimates are associated with Parkinson’s disease genetic risk

BackgroundOptical coherence tomography (OCT) is a non-invasive technique to measure retinal layer thickness, providing insights into retinal ganglion cell integrity. Studies have shown reduced retinal nerve fibre layer (RNFL) and ganglion cell inner plexiform layer (GCIPL) thickness in Parkinson’s disease (PD) patients. However, it is unclear if there is a common genetic overlap between the macula and peripapillary estimates with PD and if the genetic risk of PD is associated with changes in ganglion cell integrity estimates in young adults.MethodWestern Australian young adults underwent OCT imaging. Their pRNFL, GCIPL, and overall retinal thicknesses were recorded, as well as their longitudinal changes between ages 20 and 28. Polygenic risk scores (PRS) were estimated for each participant based on genome-wide summary data from the largest PD genome-wide association study conducted to date. We further evaluated whether PD PRS was associated with changes in thickness at a younger age. To evaluate the overlap between retinal integrity estimates and PD, we annotated and prioritised genes using mBAT-combo and performed colocalisation through the GWAS pairwise method and HyPrColoc. We used a multi-omic approach and single-cell expression data of the retina and brain through a Mendelian randomisation framework to evaluate the most likely causal genes. Genes prioritised were analysed for missense variants that could have a pathogenic effect using AlphaMissense.ResultsWe found a significant association between the Parkinson’s disease polygenic risk score (PD PRS) and changes in retinal thickness in the macula of young adults assessed at 20 and 28 years of age. Gene-based analysis identified 27 genes common to PD and retinal integrity, with a notable region on chromosome 17. Expression analyses highlighted NSF, CRHR1, and KANSL1 as potential causal genes shared between PD and ganglion cell integrity measures. CRHR1 showed consistent results across multiple omics levels.InterpretationOur findings suggest that retinal measurements, particularly in young adults, could be a potential marker for PD risk, indicating a genetic overlap between retinal structural integrity and PD. The study highlights specific genes and loci, mainly on chromosome 17, as potential shared etiological factors for PD and retinal changes. Our results highlight the importance of further longitudinal studies to validate retinal structural metrics as early indicators of PD predisposition.