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Glaucoma, a blinding eye disease with optic neuropathy, is usually associated with elevated intraocular pressure (IOP). The currently available pharmacological and surgical treatments for glaucoma have significant limitations and side effects, which include systemic reactions to medications, patient non-compliance, eye infections, surgical device failure, and damage to the eye. Here, we present Sensor-Actuator-Modulator (SAM), an engineered double mutant version of the bacterial stretch-activated mechanosensitive channel of large conductance (MscL) that directly senses tension in the membrane lipid bilayer of cells and in response, transiently opens its large nonspecific pore to release cytoplasmic fluid. The heterologously expressed mechanosensitive SAM channel acts as a tension-activated pressure release valve in trabeculocytes. In the trabecular meshwork (TM), SAM is activated by membrane stretch caused by elevated IOP. We have identified several SAM variants that are activated at physiologically relevant pressures. Using this barogenetic technology, we have demonstrated that SAM is functional in cultured TM cells, and successfully transduced in vivo in TM cells by use of AAV2/8. Further, it is effective in enhancing aqueous humor outflow facility leading to lowering the IOP in a mouse model of ocular hypertension.
Autoregulation of intraocular pressure via expression of a mechanosensitive channel of large conductance in trabecular meshwork serves as a mutation-agnostic gene therapy for glaucoma.
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Humor Acuoso , Terapia Genética , Glaucoma de Ángulo Abierto , Animales , Glaucoma de Ángulo Abierto/genética , Glaucoma de Ángulo Abierto/terapia , Humor Acuoso/metabolismo , Humanos , Malla Trabecular/metabolismo , Presión Intraocular , RatonesRESUMEN
Background: Continuity of care is one of the main principles of family medicine, described as a relationship with a single provider that extends beyond a single illness episode. This retrospective study, conducted at King Saud University Family Medicine Center in Riyadh, Saudi Arabia, aimed to investigate the impact of having a regular primary care provider on clinical outcomes and preventive service delivery for patients with diabetes and/or hypertension. Methods: The study, spanning 2017 to 2019, included 400 patients diagnosed with diabetes and/or hypertension for at least six months before the 6-month pre-attachment period to regular family medicine physicians in 2018. Data before and after attachment for at least six months were compared using electronic health records. Results: The mean age of the patients was 60.9, with a predominant female representation (66.8%) and 90.7% Saudis. Results indicated a significant improvement in glycated hemoglobin (HbA1c) levels (p = 0.005) and systolic blood pressure (p = 0.014) post-attachment. Preventive service delivery saw notable enhancements, with increased colon cancer screening (p = 0.03), breast cancer screening (p < 0.001), and retinal screening (p < 0.001) post-attachment. Conclusion: This study's findings underscore the importance of continuity of care in chronic disease management and provide valuable and promising insights into the Saudi healthcare context, aligning with the Saudi Ministry of Health's vision for universal access to regular primary care providers.
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This article discusses the rarity of primary cardiac tumors, particularly angiosarcomas, accounting for 10% of primary cardiac neoplasms. The article highlights the challenge of early diagnosis due to nonspecific symptoms. The importance of sectional imaging, particularly computed tomography (CT) scans, in emergent situations is emphasized. Teaching point: Despite the rarity of primary cardiac tumors, radiologists should remain alert, especially when pericardial effusion is present.
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BACKGROUND AND PURPOSE: There is a high frequency of frailty in patients with musculoskeletal pain. Pain from osteoarthritis and lower back pain may be associated with frailty. However, the future risk of frailty among older adults with pain remains unclear. Thus, the primary objective of this study was to examine the association between musculoskeletal pain and the risk of becoming prefrail and frail in older adults. PARTICIPANTS AND METHODS: A secondary analysis was performed using data from baseline and 1-, 2-, 3-, 4-, 6-, and 8-year follow-ups of the Osteoarthritis Initiative (OAI). The OAI recruited participants from 4 clinical sites in the United States, between February 2004 and May 2006. A self-reported questionnaire was used to determine the baseline musculoskeletal pain status in older adults (n = 1780) 65 years and older, including pain in the lower back, hip, knee, and at 2 or more sites. Using the Fried phenotypic criteria, participants were classified as nonfrail, prefrail, and frail at each period over 8 years. RESULTS: After adjusting for age, sex, race, education, marital status, annual income, smoking status, comorbidities, and body mass index, binary logistic regression modeling using generalized estimating equations revealed that in older adults musculoskeletal pain in the lower back and at multiple sites was associated with a slightly but significantly decreased risk of prefrailty over time (adjusted odds ratio [AOR] = 0.98, 95% CI = 0.95-0.99, P = .019; AOR = 0.96, CI = 0.92-0.99, P = .032). The association between musculoskeletal pain and frailty among older adults was not statistically significant (all P > .05). CONCLUSIONS: Musculoskeletal pain did not independently significantly increase the risk of prefrailty or frailty over time. It remains possible that when musculoskeletal is combined with other factors, the risk of prefrailty and frailty may be heightened. Further research into the combination of characteristics that best predict prefrailty and frailty, including but not limited to musculoskeletal pain, is warranted.
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OBJECTIVES: Early diagnosis of Parkinson's disease (PD) is critical for optimal treatment. However, the predictive potential of physical and mental health in PD is poorly characterized. METHODS: We evaluated the potential of multiple demographic, physical, and mental factors in predicting the future onset of PD in older adults aged 50 years or older from 15 European countries. Individual study participants were followed over four waves of the Survey of Health, Ageing, and Retirement in Europe (SHARE) from 2013-2020. RESULTS: Of 57,980 study participants, 442 developed PD during the study period. We identified male sex and advancing age from the sixth decade of life onward as significant predictors of future PD. Among physical factors, a low handgrip strength (HGS; men <27 kg, women <16 kg), being bothered by frailty, and recent falls were significantly associated with future PD. Among mental factors, a higher depression (Euro-D depression score >6) emerged as an independent predictor of future PD. Finally, the presence of hypertension or Alzheimer's disease (AD) increases the risk of future PD. CONCLUSIONS: Altogether, male sex, advancing age, low HGS, frailty, depression, hypertension, and AD were identified as critical risk factors for future PD. Our results may be useful in the early identification and treatment of populations at risk for PD.
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Enfermedad de Alzheimer , Fragilidad , Hipertensión , Enfermedad de Parkinson , Humanos , Masculino , Femenino , Anciano , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/complicaciones , Salud Mental , Fragilidad/complicaciones , Fuerza de la Mano , Europa (Continente)/epidemiología , BiomarcadoresRESUMEN
This systematic review aims to summarize the findings from all clinical randomized trials assessing the efficacy of potential neuroprotective agents in influencing the outcomes of acute spinal cord injuries (SCI). Following the PRISMA guidelines, we conducted comprehensive searches in four electronic databases (PubMed, Scopus, Cochrane Library, and Web of Science) up to September 5th, 2023. Our analysis included a total of 30 studies. We examined the effects of 15 substances/drugs: methylprednisolone, tirilazad mesylate, erythropoietin, nimodipine, naloxone, Sygen, Rho protein antagonist, granulocyte colony-stimulating factor, autologous macrophages, autologous bone marrow cells, vitamin D, progesterone, riluzole, minocycline, and blood alcohol concentration. Notable improvements in neurological outcomes were observed with progesterone plus vitamin D and granulocyte colony-stimulating factor. In contrast, results for methylprednisolone, erythropoietin, Sygen, Rho Protein, and Riluzole were inconclusive, primarily due to insufficient sample size or outdated evidence. No significant differences were found in the remaining evaluated drugs. Progesterone plus vitamin D, granulocyte colony-stimulating factor, methylprednisolone, Sygen, Rho Protein, and Riluzole may enhance neurological outcomes in acute SCI cases. It is worth noting that different endpoints or additional subgroup analyses may potentially alter the conclusions of individual trials. Therefore, certain SCI grades may benefit more from these treatments than others, while the overall results may remain inconclusive.
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Eritropoyetina , Fármacos Neuroprotectores , Traumatismos de la Médula Espinal , Humanos , Fármacos Neuroprotectores/uso terapéutico , Riluzol/uso terapéutico , Nivel de Alcohol en Sangre , Progesterona/uso terapéutico , Traumatismos de la Médula Espinal/tratamiento farmacológico , Metilprednisolona/uso terapéutico , Eritropoyetina/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Vitamina D/uso terapéuticoRESUMEN
In neurodegenerative diseases, using a single molecule that can exert multiple effects to modify the disease may have superior activity over the classical "one molecule-one target" approach. Herein, we describe the discovery of 6-hydroxybenzothiazol-2-carboxamides as highly potent and selective MAO-B inhibitors. Variation of the amide substituent led to several potent compounds having diverse side chains with cyclohexylamide 40 displaying the highest potency towards MAO-B (IC50 = 11 nM). To discover new compounds with extended efficacy against neurotoxic mechanisms in neurodegenerative diseases, MAO-B inhibitors were screened against PHF6, R3 tau, cellular tau and α-synuclein (α-syn) aggregation. We identified the phenethylamide 30 as a multipotent inhibitor of MAO-B (IC50 = 41 nM) and α-syn and tau aggregation. It showed no cytotoxic effects on SH-SY5Y neuroblastoma cells, while also providing neuroprotection against toxicities induced by α-syn and tau. The evaluation of key physicochemical and in vitro-ADME properties revealed a great potential as drug-like small molecules with multitarget neuroprotective activity.
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Neuroblastoma , Enfermedades Neurodegenerativas , Humanos , Inhibidores de la Monoaminooxidasa/farmacología , Inhibidores de la Monoaminooxidasa/química , Neuroprotección , Monoaminooxidasa/metabolismo , Relación Estructura-ActividadRESUMEN
The objective was to assess the knowledge, attitudes, and practices of nurses toward the prevention of falls in older hospitalized patients. A cross-sectional study employing a 54-item questionnaire was conducted on 370 nurses at a tertiary care referral center. The mean age of the study population was 36.3 ± 7.7 years, with the majority being females (282; 76.8%). Most of them had attended fall prevention training (335; 90.5%). More than 98% knew fall prevention policies and safety goals, according to their response to a fall and risk assessment, but were less aware of the risk factors of falls, such as recurrent falls (61%), depression (44%), and lower-extremity numbness (40.5%). Similarly, 99% had positive attitudes toward risk assessment, fall prevention intervention, and response to a fall. Around 55% thought they were responsible for patients' falls, and 96% felt the need to undergo more training on fall prevention. Furthermore, 92% strictly followed fall prevention policies and 85.4% followed the color-coding system for high-risk patients. Despite the preventive measures in place, 33% encountered patient falls, and 82.2% experienced unwitnessed patient fall incidents in their units. Although the nurses had higher levels of knowledge about the policies, they lacked information on the risk factors. There is a significant scope that warrants great attention concerning the adherence to guidelines and the provision of fall prevention training programs, with a focus on the intrinsic causative factors of falls.
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Background: Anemia is a public health issue that affects both industrialized and developing nations. Childhood anemia has severe consequences, including reduced growth, poor motor and cognitive development, and increased death and morbidity. Objective: This study aims to determine sociodemographic factors associated with the severity of anemia among under-five children in Kut City. Methods: A cross-sectional study with a convenience sample (non-probability) was conducted among 264 children admitted to hospitals in Kut City, from September 1st, 2022, to March 1st, 2023. Data were collected via questionnaires, and descriptive and inferential statistics were used to evaluate the data. Results: The total number of children participating in the study was 264, with 39.0% having mild anemia and 60.0% having moderate anemia, according to the World Health Organization classification of anemia. The results showed that the children most at risk of developing anemia were within 4 years of age and had a lower mean hemoglobin level than the rest of the age groups of the children participating in the study, compared to the mean+standard deviation (SD) (9.46+0.99). Boys are more affected than girls, and those who reside in rural areas have lower hemoglobin (HB) percentages with a mean+SD of (9.21+0.93). Unemployed mothers who read and write had the lowest HB percentage. In contrast, parents with primary education and government jobs have the lowest percentage of HB. Children of married mothers are more affected by anemia. Families with high overcrowding showed the lowest rate of HB. They experienced low socioeconomic status as a result. The degree of anemia was significantly correlated with the child's age, residence, mother's educational level, father's job, and socioeconomic position. Conclusion: This study concludes a significant association between the severity of anemia and sociodemographic factors, both unmodifiable (age) and modifiable (residence, mothers' education, fathers' jobs, and economic and social status). Children with modifiable risk factors need to have their anemia risk constantly evaluated.
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Suspended sediment concentration (SSC) in water increases temperature and turbidity, limits the photosynthesis of aquatic plants, and reduces biologically available oxygen. It is important to study SSC in the coastal waters of the Arabian Gulf. Thus, this study mapped the SSC of coastal water between Al Arish and Al Ghariyah in northern Qatar using the spectral bands of the MultiSpectral Imager (MSI) of Sentinel-2 by calculating the Normalized Difference Suspended Sediment Index and Normalized Suspended Material Index. The results are studied using the Normalized Difference Turbidity Index and Modified Normalized Difference Water Index. The mapping of SSC in the water using NDSSI showed the presence of a high concentration of suspended sediments between Al Arish and Al Mafjar and a low concentration between Al Mafjar and Al Ghariyah. The mapping of NSMI showed values between 0.012 (clear water) and 0.430 (more suspended material) for the occurrence of suspended materials and supported the results of NDSSI. The study of turbidity using an NDTI image showed turbidity index values ranging from -0.44 (clear water) to 0.12 (high turbidity) and confirmed the occurrence and distribution of suspended sediments and materials in the water. The MNDWI image was able to discriminate clear water with bright pixels from silty sand and mud flats. The relationships between NDSSI, NSMI, and NDTI were correlated with in-situ measurements and studied to find suitable indices to map SSC. Regression analyses showed the strongest relationship between NSMI and NDTI (R2 = 0.95) next to NDSSI and NDTI, where NDTI had the strongest effect on NDSSI (R2 = 0.86). The satellite data results were evaluated by studying the physical parameters and spatial distribution of suspended sediments in the surface and bottom waters. In addition, the grain size distributions, mineral identification, and chemical element concentrations in the bottom sediment samples were studied.
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OBJECTIVES: The relationship between handgrip strength (HGS) and quality of life is inconsistent. The purpose of this study was to investigate the potential association between HGS and quality of life in the settings of ageing and Alzheimer's disease (AD). METHODS: We investigated the HGS, CASP-12 (control, autonomy, self-realization, and pleasure) measure of quality of life, and physical capacity in European adults above 50, including controls (n = 38,628) and AD subjects (n = 460) using the survey of health, ageing, and retirement in Europe (SHARE; 2022). RESULTS: AD subjects exhibited lower HGS and CASP-12 scores than controls (both p < 0.05). Participants with higher CASP-12 quartiles had higher HGS in controls but not in AD subjects. A linear positive relation was found between HGS and CASP-12 in controls (0.0842, p < 0.05) but not in AD subjects (0.0636, p = 0.091). There was no effect of gender on this finding. Lastly, we found significant negative associations of difficulties walking, rising from chair, climbing stairs, and fatigue with CASP-12 scores in controls and AD subjects (all p < 0.05). CONCLUSIONS: Altogether, HGS was not associated with quality of life in individuals with AD. Conversely, difficulties in activities of daily living seem to be negatively associated with quality of life; thus, strategies are recommended to improve physical capacity.
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Enfermedad de Alzheimer , Calidad de Vida , Humanos , Actividades Cotidianas , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/epidemiología , Fuerza de la Mano , Europa (Continente)/epidemiologíaRESUMEN
Purpose: Smartphone addiction is prevalent among medical students, and there is a concern that the coronavirus disease 2019 (COVID-19) pandemic fueled a rise in smartphone addiction. Earlier studies suggest a link between excessive smartphone usage and negative outcomes such as depression, stress, and reduced academic achievement. However, there is a dearth of both local studies in Saudi Arabia and studies conducted during the COVID-19 pandemic exploring the prevalence of smartphone addiction and its association with academic performance, depression, and perceived stress, which is the purpose of the current study. Methods: In 2021, a cross-sectional research project took place among medical students at King Saud University and the Vision Colleges located in Riyadh, Saudi Arabia. An online self-administered questionnaire consisting of demographic variables, grade point average (GPA), the Patient Health Questionnaire-9 (PHQ-9), the Perceived Stress Scale-4 (PSS-4), and the Smartphone Addiction Scale-Short Version (SAS-SV) was deployed. Results: Three hundred and fifteen students participated. Around 47.9% of students reported smartphone addiction, and the mean SAS-SV score was 32.31 ± 12.01 points. Both PHQ-9 and PSS-4 scores showed a significant positive correlation with the SAS-SV score (r = 0.216, p < 0.001 and r = 247, p < 0.001, respectively), while GPA did not (r = -0.027, p = 0.639). An adjusted analysis showed that the PSS-4 score was positively associated with the SAS-SV score (odds ratio (OR) = 1.206, p < 0.001), while the PHQ-9 score was not (OR = 102, p = 0.285). Conclusions: Smartphone addiction is prevalent among medical students and associated with perceived stress. Additional research is required to gain a deeper comprehension of this issue and to assess the success of intervention initiatives aimed at encouraging healthy smartphone usage, particularly in times of crisis like the COVID-19 pandemic.
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COVID-19 , Estudiantes de Medicina , Humanos , Arabia Saudita/epidemiología , Pandemias , Estudios Transversales , Trastorno de Adicción a Internet , COVID-19/epidemiologíaRESUMEN
Background: Allergic rhinitis (AR) is considered one of the most common reasons for patients visiting primary health care clinics. Physicians' adherence to management guidelines for AR results in better patient outcomes. Therefore, the present study aimed to assess the knowledge, attitudes, and practices of primary health care practitioners (PHCPs) towards allergic rhinitis guidelines in Saudi Arabia. Methods: This observational cross-sectional study conducted from August 2021 to November 2021 included 282 primary care physicians across all regions of Saudi Arabia. We used a two-part, validated, self-administered Perception Attitude and Practice of Primary Care Practitioners questionnaire. The first part was demographics, and the second part comprised three domains (perception, attitude, and practice) including 48 items. Statistical Package for the Social Sciences (SPSS), version 21 was used to analyze the data. Results: Most of the 282 physicians were Saudis (79%). Allergic rhinitis and its impact on asthma (ARIA) guidelines were recognized by 71% of the physicians. Second-generation oral antihistamines were considered the safest drug by the majority (82%), followed by intranasal corticosteroids (75.2%). Most physicians diagnosed AR based on clinical history (95%), while (43%) utilized allergy testing. Intranasal corticosteroids were the most preferred treatment option (70%) followed by second-generation and first-generation oral antihistamines (66% and 55%, respectively). Conclusion: Our study demonstrates the importance of education and awareness for PHCPs managing AR. ARIA guidelines should be implemented as a standard of care for AR, as PHCPs are the first ones to encounter patients with AR, to improve outcomes and avoid undertreatment and complications.
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Calcium sulfate minerals are abundant in nature - on Earth and on Mars - and important in several fields of material sciences. With respect to gypsum and bassanite, anhydrite represents the anhydrous crystalline phase in the CaSO4-H2O system. Despite years of research, the formation of anhydrite in the laboratory at low temperature remains challenging and, in the geological record, this mineral is mostly interpreted as a secondary phase that form through metamorphic dehydration of gypsum. Here, we present the results of laboratory precipitation experiments showing that anhydrite can form at 35 °C from evaporated seawater through a microbially influenced mineralization process. The experiments were conducted in the presence of extracellular polymeric substances (EPS) produced by bacterial strains isolated from a modern evaporitic environment, the Dohat Faishakh sabkha in Qatar. Without organic molecules, only gypsum formed in parallel control experiments. This finding provides a possible explanation for the origin of several natural occurrences of anhydrite that cannot be satisfactorily explained by existing models and reveals a new precipitation pathway that may have industrial applications.
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Hereditary elliptocytosis (HE) and pyropoikilocytosis (HPP) are considered a group of hemolytic anemias (HE/HPP) due to inherited abnormalities of erythrocyte membrane proteins with a worldwide distribution. Most cases are associated with molecular abnormalities linked to spectrin, band 4.1, and ankyrin. The present study aimed to identify significant molecular signatures on a target panel of 8 genes using whole exome sequencing (WES) in 9 Bahraini patients with elliptocytosis. Case selection was based on presence of anemia not associated with iron deficiency or hemoglobinopathy and demonstrating > 50% elliptocytes in blood smears. The c.779 T > C mutation of SPTA1 (Spectrin alpha), which is a known deleterious missense mutation that inhibits normal association of spectrin molecules to form tetramers, was seen in 4 patients in homozygous (n = 1) and heterozygous (n = 3) states. The αLELY abnormality in association with compound heterozygous mutations in SPTA1 was present in 5 patients (2 associated with the SPTA1 c.779 T > C variant; 3 with c.3487 T > G and various other SPTA1 mutations of uncertain/unknown significance). Seven patients had SPTB (Spectrin beta) mutations, predicted as likely benign by in silico analysis. A novel EPB41 (Erythrocyte Membrane Protein Band 4.1) mutation with potential deleterious impact was also seen. Finally, 2 cases showed an InDel (insertion-deletion mutations) abnormality in the gene that codes for the mechanosensitive ion-channel PIEZO (Piezo Type Mechanosensitive Ion Channel Component 1). PIEZO mutations are reported to cause red cell dehydration but have not been previously described in HE/HPP. Results of this study confirm the involvement of previously reported abnormalities in SPTA1 and suggest possible involvement of other candidate genes in a disorder involving polygenic interactions.
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Eliptocitosis Hereditaria , Humanos , Eliptocitosis Hereditaria/genética , Espectrina/genética , Mutación , Eritrocitos AnormalesRESUMEN
OBJECTIVES: To examine the association between the number of non-communicable diseases (NCDs) and physical activity (PA) in older adults visiting primary healthcare centers (PHCCs) in Jizan, Saudi Arabia. METHODS: This cross-sectional study was carried out on men and women aged ≥60 who visited PHCCs, Jizan City between June and September 2021. Eleven self-reported NCDs were identified and summed to produce a single score, and PA scores were calculated based on the self-reported PA Scale for the Elderly (PASE). Multiple linear regression models were used to examine the association between the number of NCDs and PA in the included population. RESULTS: In total, 94 participants were included in this study. Of these, 62 were men, and 32 were women. The mean age was 67.29±6.58 years, and the mean PASE score was 53.67±29.72. A significant negative association was found between the number of NCDs and PA, even after a fully adjusted analysis. CONCLUSION: This study found a significant inverse association between the number of NCDs and PA in older adults. In addition, age was associated with lower PA, even among older adults. PA should be recommended to older adults to prevent or reduce the number of NCDs. Future research should focus on examining cause-and-effect associations at a national level.
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Enfermedades no Transmisibles , Masculino , Anciano , Humanos , Femenino , Persona de Mediana Edad , Arabia Saudita/epidemiología , Enfermedades no Transmisibles/epidemiología , Estudios Transversales , Ejercicio Físico , Atención Primaria de SaludRESUMEN
Inflammatory bowel diseases (IBD) result from genetic and environmental factors. The two clinical manifestations of inflammatory bowel disease are ulcerative colitis and Crohn's disease (IBD). Numerous studies have demonstrated a link between immune system molecules' single nucleotide polymorphisms (SNPs) and the incidence of IBD. The study aimed to examine the potential impact of the SNPs NOD2 rs2066844 and ATG16L1 rs2241880 in a group sample of Iraqi IBD patients. The AG genotype for rs2241880 was associated with an increased risk for CD (P=0.1) and a negative association with UC, whereas the AA genotype presents less in CD patients and a negative association with UC (P=0.89). For this SNP, the G allele was associated with the risk of CD but not for UC. For the rs2066844, there were no significant differences for NOD2 in both CD and UC, and associations between variation and diseases were not observed.
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Colitis Ulcerosa , Enfermedades Inflamatorias del Intestino , Humanos , Proteínas Relacionadas con la Autofagia/genética , Colitis Ulcerosa/genética , Inflamación , Enfermedades Inflamatorias del Intestino/genética , Proteína Adaptadora de Señalización NOD2/genética , Polimorfismo de Nucleótido SimpleRESUMEN
War and cancer have been intertwined in Iraq for over three decades, a country where the legacies and ongoing impacts of conflict have been commonly associated with both increased cancer rates as well as the deterioration of cancer care. Most recently, the Islamic State of Iraq and the Levant (ISIL) violently occupied large portions of the country's central and northern provinces between 2014 and 2017, causing devastating impacts on public cancer centers across central and northern Iraq. Focusing on the five Iraqi provinces previously under full or partial ISIL occupation, this article examines the immediate and long-term impacts of war on cancer care across three periods (before, during, and after the ISIL conflict). As there is little published data on oncology in these local contexts, the paper relies primarily upon the qualitative interviews and lived experience of oncologists serving in the five provinces studied. A political economy lens is applied to interpret the results, particularly the data related to progress in oncology reconstruction. It is argued that conflict generates immediate and long-term shifts in political and economic conditions that, in turn, shape the rebuilding of oncology infrastructure. The documentation of the destruction and reconstruction of local oncology systems is intended to benefit the next generation of cancer care practitioners in the Middle East and other conflict-affected regions areas in their efforts to adapt to conflict and rebuild from the legacies of war.
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BACKGROUND: De novo neuroendocrine prostate cancer (NEPC) and treatment-emergent neuroendocrine prostate cancer (T-NEPC) are rare diseases with a poor prognosis. After first-line platinum chemotherapy, there is no consensus on second-line treatments. PATIENTS AND METHODS: Patients with a pathologic diagnosis of de novo NEPC or T-NEPC between 2000 and 2020 who received first-line platinum and any second-line systemic therapy were selected and standardized clinical data was collected via the electronic health record at each institution. The primary endpoint was overall survival (OS) based on second-line therapy. Secondary endpoints included objective response rate (ORR) to second-line therapy, PSA response, and time on treatment. RESULTS: Fifty-eight patients (32 de novo NEPC, 26 T-NEPC) from 8 institutions were included. At de novo NEPC or T-NEPC diagnosis, the overall cohort had a median age of 65.0 years (IQR 59.2-70.3) and median PSA of 3.0 ng/dL (IQR 0.6-17.9). Following first-line platinum chemotherapy, 21 patients (36.2%) received platinum chemotherapy, 10 (17.2%) taxane monotherapy, 11 (19.0%) immunotherapy, 10 (17.2%) other chemotherapy, and 6 (16.2%) other systemic therapy. Among 41 evaluable patients, the ORR was 23.5%. The mOS after start of second-line therapy was 7.4 months (95% CI 6.1-11.9). CONCLUSIONS: In this retrospective study, patients with de novo NEPC or T-NEPC who received second-line therapy were treated with wide variety of treatment regimens, reflecting the lack of consensus in this setting. Most patients received chemotherapy-based treatments. Overall prognosis was poor and ORR was low in the second line regardless of treatment choice.
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Antígeno Prostático Específico , Neoplasias de la Próstata , Masculino , Humanos , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Platino (Metal) , Neoplasias de la Próstata/patología , PronósticoRESUMEN
Many surgical solutions for knee flexiondeformity in the pediatric population alter the anatomical bony alignment in the distal femur. Posterior knee capsule release has been presented as an alternative surgical procedurethat maintains the anatomical shape of relevant bones while solving the issue of knee flexion contracture. The aim of this study is to assess the results of a double-incision posteriorknee capsulotomy release performed on pediatric patients with neuromuscular or congenital severe knee flexion deformity. Thirty cases (24 patients, mean age 7.4 years) of severe knee flexion contractures were retrospectively analyzed in a cohort of varying underlying conditions (including spina bifida, muscular dystrophy, cerebral palsy, sclerodermia, and congenital patellar dislocations). Posterior knee release was performed through medial and lateral short incisions with subsequent serial casting. Range and pace of correction as well as the complication rate were recorded. Follow-up information (>1 year) included functionality (FMS scale) and pain (Kujala/Knee Injury Osteoarthritis Score [KOOS]) scales. Significant correction in the knee position was achieved in all analyzed knees (from mean 40.2° to 0.7°; P < 0.01). Twenty-nine out of 30 cases achieved correction by 7 days postoperatively (average number of casts: 1.93 ± 1.05). Overall complication rate in the analyzed cohort reached 6.7% (2/30 cases; double metaphyseal fracture and arthrofibrosis). At follow-up (22.3 months on average), functional ambulation and pain parameters improved drastically, with no further complications observed. Double-incision posterior knee release is an effective method of knee contracture release, which does not affect the axial alignment of the distal femoral bone. Thus, posterior knee release should be considered as potential alternatives to osteotomies and eight-plate corrections, which are currently the basic methods of knee contracture treatment.