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Fourteen species of monopisthocotyls were reported from the gills of Triportheus albus Cope (Characiformes: Triportheidae) collected from the Itaya River, Peru. Nine species belonged to Anacanthorus Mizelle & Price, 1965: seven previously described species: Anacanthorus acuminatus Kritsky, Boeger & Van Every, 1992, Anacanthorus alatus Kritsky, Boeger & Van Every, 1992, Anacanthorus bellus Kritsky, Boeger & Van Every, 1992, Anacanthorus euryphallus Kritsky, Boeger & Van Every, 1992, Anacanthorus quinqueramus Kritsky, Boeger & Van Every, 1992, Anacanthorus formosus Kritsky, Boeger & Van Every, 1992, and Anacanthorus ramulosus Kritsky, Boeger & Van Every, 1992, and two new species described herein. Three species belonged to Ancistrohaptor Agarwal & Kritsky, 1998: Ancistrohaptor falciferum Agarwal & Kritsky, 1998, Ancistrohaptor falcunculum Agarwal & Kritsky, 1998, and Ancistrohaptor forficata Diniz, de Sousa, Yamada & Yamada, 2025; and two to Jainus Mizelle, Kritsky & Crane, 1968: Jainus iquitensis Morey, Viana, Chota & Chero, 2025 and Jainus sardinae Morey, Viana, Chota & Chero, 2025. Anacanthorus itayensis n. sp. is characterized by a long sclerotized sigmoid male copulatory organ (MCO) with submedial cirral "feather" and by a four-branched accessory piece in which the second branch terminates in a fish-like fin, the others bifurcate into sub-branches with pointed tips. Anacanthorus ypsiloniformis n. sp. is characterized by an elongate, slightly conical MCO curving ventrally and terminating in a rounded, slightly tapered distal tip bearing a dense crown-like cluster with submedial small spines, and by a distinctively Y-shaped accessory piece with two divergent arms arising proximally: one broader and blunt-ended with a comb-like denticulate distal margin, the other narrower and more rounded distally. This study constitutes the first comprehensive record of monopisthocotyls from T. albus in Peru and documents one of the most species-rich dactylogyrid assemblages reported from a single host species of Triportheus Cope in the Neotropical region.
Correctional climate-the perceptions staff and incarcerated people hold about their institution-can influence well-being for everyone living and working in prison. This study explores differences in perceptions of safety, quality of sleep, psychological and emotional wellness, physical health, and overall life outlook among 1,148 security staff, non-security staff, and incarcerated individuals across five Minnesota Department of Corrections facilities. Results indicate that both staff groups report significantly greater safety and sleep quality outcomes than incarcerated people, while security staff also reported better emotional wellness than the incarcerated population. No differences emerged across groups regarding perceived psychological wellness, physical health, or life outlook. These findings highlight both shared experiences and key disparities within correctional environments, underscoring opportunities to improve conditions, support workforce well-being, and advance institutional policies that benefit all people in prison settings. How Prison Staff and Incarcerated People View Safety, Health, and Life in PrisonPrisons are environments where both staff and incarcerated people live or work every day. How people feel about safety, health, and well-being in these settings, often called the correctional climate, can affect everyone inside the facility. Understanding these perceptions can help improve conditions for both staff and incarcerated individuals. This study examined how people in five prisons in Minnesota view their safety, sleep quality, emotional and psychological well-being, physical health, and overall outlook on life. The study included responses from 1,148 people: correctional security staff, non-security staff, and incarcerated individuals. The results showed some important differences. Both security staff and non-security staff reported feeling safer and said they slept better than incarcerated people. Security staff also reported better emotional well-being than incarcerated individuals. However, the three groups reported similar levels of psychological well-being, physical health, and general outlook on life. These findings suggest that people in prisons share some similar experiences but also face different challenges. Understanding these similarities and differences can help correctional leaders develop policies and programs that improve safety, well-being, and working and living conditions for everyone in prison facilities.
SSGJ-608 is an anti-interleukin-17A monoclonal antibody with high specificity and high affinity and has shown promising efficacy in treatment of moderate-to-severe psoriasis in preliminary trials. This multicenter, randomized, open-label, phase 3 trial aimed to further evaluate SSGJ-608 at different dosing intervals (80mg every two weeks and 160mg every four weeks) in patients with moderate-to-severe plaque psoriasis. A total of 770 patients with moderate to severe plaque psoriasis were randomly assigned (1:1) to receive subcutaneous injections of 80mg of SSGJ-608 every two weeks (Q2W) after a starting dose of 160mg at week 0(608A group), or 160mg of SSGJ-608 every four weeks (Q4W) (608 B group) for 12 weeks. Efficacy was assessed by PASI75 and sPGA 0 or 1 response rates at week 12 as co-primary endpoints, and proportion of patients who achieved PASI90, PASI100 or sPGA score of 0 at week 12 as secondary endpoints. The safety profile was also evaluated. At week12, the proportions of patients achieving PASI75 (92.7% vs. 95.1%) and sPGA 0/1 (80.3% vs. 79.0%) were comparable between the two SSGJ-608 dose regimens. The PASI90, PASI100 and sPGA 0 response rates were 81.0% vs.82.3%, 49.4% vs. 47.5%, and 49.4% vs.47.3% in the 608A group and the 608B group, respectively. In the subgroup of patients previously treated with anti-IL-17 therapy, SSGJ-608 also achieved high clinical response rates at week12. The most common TEAEs were hypertriglyceridemia, upper respiratory tract infection, hyperuricemia, increased alanine aminotransferase and hypercholesterolemia. Both treatment groups demonstrated a favorable safety profile and no new safety signals were identified. SSGJ-608 was highly effective for treating patients with moderate-to-severe plaque psoriasis at 80mg Q2W and 160mg Q4W in a larger population, especially in patients previously treated with anti-IL-17 therapy, and exhibited a favorable tolerability profile in Chinese patients with moderate-to-severe plaque psoriasis. https://clinicaltrials.gov/, identifier NCT06299982.
Pregnancy is a wonderful milestone in every female's life associated with hormonal and physical changes to prepare women for motherhood. Most of the women report signs and symptoms of one or other minor ailments throughout the pregnancy. Although they are not dangerous, their presence distracts the woman from feeling of comfort and wellbeing. The study was conducted to assess the effectiveness of antenatal craft class on management of selected minor ailments during pregnancy among primigravidae. A quasi-experimental study was conducted on primigravidae women visiting antenatal out-patient department at a tertiary care teaching hospital. A total of 60 primigravidae (30 in each group) with a gestational age between 28 and 36 weeks were selected by the nonprobability convenience sampling technique. Antenatal craft class was taken for the experimental group, whereas the control group received routine antenatal care. Data were collected by using the tools: visual analog scale for back pain and leg cramps, multidimensional assessment of fatigue scale for fatigue and self-structured heartburn severity, and frequency rating scale for heartburn. Descriptive and inferential statistics were used to analyze the data. Significant improvement in the management of minor ailments such as back pain, leg cramps, fatigue, and heartburn (p = P < 0.001) was observed in the experimental group as compared to the control group. Intake of spicy food (p = P < 0.001 1) and intake of fast food (P = 0.005) were significantly associated with severity of heartburn; place of residence (P = 0.04) and intake of fast food (P = 0.03) were significantly associated with frequency of heartburn in the experimental group. However, in the control group, exercise was associated with level of back pain (P = 0.03); type of diet (P = 0.03) and intake of fast food (P = 0.01) were associated with severity of heartburn. Antenatal craft class was effective in managing the minor ailments like back pain, leg cramps, heartburn, and fatigue during pregnancy. It suggests that antenatal craft class acts as a primary health care to reduce pregnancy-induced minor discomforts and to improve their quality of life at the community level.
To observe the role of tyrosine hydroxylase (TH)-positive neurons in the nucleus tractus solitarius (NTS) and locus coeruleus (LC) in electroacupuncture (EA)-mediated improvement of blood-brain barrier (BBB) damage in APP/PS1 mice, so as to explore the mechanism of the NTSTH-LC neural circuit underlying the effect of EA on prevention and treatment of Alzheimer's disease (AD). (1) Eight 4-month-old male C57BL/6 mice served as the control group, and 16 age-matched male APP/PS1 mice were randomly divided into the model and EA groups (n=8). The EA group received EA stimulation at "Neiguan" (PC6) and "Jianshi" (PC5) once every other day for 4 weeks. After intervention, Morris water maze and novel object recognition tests were used to evaluate learning and memory abilities. Western blot was performed to detect the expression levels of hippocampal tight junction proteins, including Occludin, Claudin-5, and zonula occludens-1 (ZO-1). Immunofluorescence was used to assess the co-localization of TH/c-Fos in NTS and LC, as well as TH/norepinephrine (NE) co-localization in LC. (2) Five TH-cre mice received retrograde tracing virus injection into LC to observe whether TH-positive neurons in NTS project to LC. (3) Twenty-one 7-month-old APP/PS1 mice were injected with chemogenetic activation virus (AAV2/9-hSyn-DIO-hM3D-mCherry-WPRE-hGH-pA) or empty virus (AAV2/9-Ef1α - DIO-mCherry-WPRE-hGH-pA) into the NTS, and AAVretro-TH-CRE-WPRE-hGH-pA virus into the LC. After 21 d of virus expression, 6 mice injected with empty virus were taken as mCherry+CNO+EA group;3 mice from the activation virus group were randomly selected for brain slice patch-clamp to verify virus functionality. The remaining mice were randomly divided into 2 groups (n=6):hM3D+CNO+EA, and hM3D+saline+EA groups. EA was applied to PC6 and PC5 once daily for 15 d. After intervention, learning and memory abilities were evaluated by Morris water maze and novel object recognition tests. BBB permeability was detected by Evans blue (EB) staining. Immunofluorescence was used to measure TH/c-Fos and TH/NE co-localization in the LC. (1) Compared with the control group, the model group showed significantly impaired learning and memory abilities (P<0.01), decreased expressions of hippocampal Occludin, Claudin-5, and ZO-1 (P<0.01), and increased TH/c-Fos co-localization (c-Fos expression in TH-positive neurons) in NTS and LC, as well as TH/NE co-localization in LC (P<0.01). Compared with the model group, the EA group exhibited improved learning and memory abilities (P<0.05, P<0.01), increased expressions of hippocampal tight junction proteins (P<0.01), and reduced TH/c-Fos and TH/NE co-localization (P<0.01, P<0.05). (2) Retrograde tracing confirmed that TH-positive neurons in NTS project to LC. (3) Compared with the mCherry+CNO+EA group and hM3D+saline+EA group, the hM3D+CNO+EA group showed significantly impaired learning and memory (P<0.01), increased EB content in brain tissue, and elevated TH/c-Fos and TH/NE co-localization in the LC (P<0.01). EA at PC6 and PC5 can ameliorate BBB damage and learning/memory deficits in AD mice, and its mechanism may be related to inhibiting the activation of the NTSTH-LC neural circuit. 目的: 观察孤束核（NTS）中酪氨酸羟化酶（TH）神经元及蓝斑（LC）在电针改善APP/PS1小鼠血脑屏障（BBB）损伤中的作用，探讨电针防治阿尔茨海默病（AD）的NTSTH-LC神经环路机制。方法: （1）8只4月龄雄性C57BL/6小鼠为对照组，16只同月龄雄性APP/PS1小鼠随机分为模型组、电针组（n=8）。电针组予电针刺激“内关”“间使”，隔日1次，共4周。干预结束后，以Morris水迷宫、新物体识别实验评估各组小鼠学习记忆能力，Western blot法检测海马闭锁蛋白（Occludin）、紧密连接蛋白-5（Claudin-5）、闭锁小带蛋白-1（ZO-1）表达水平，免疫荧光染色法检测NTS和LC中TH/c-Fos共定位、LC中TH/去甲肾上腺素（NE）共定位表达情况。（2）5只TH-cre小鼠，LC注射逆行示踪病毒，观察NTS中的TH神经元是否投射到LC。（3）21只7月龄APP/PS1小鼠，NTS注射化学遗传激活病毒（AAV2/9-hSyn-DIO-hM3D-mCherry-WPRE-hGH-pA）或空载病毒（AAV2/9-Ef1α-DIO-mCherry-WPRE-hGH-pA），LC注射AAVretro-TH-CRE-WPRE-hGH-pA病毒，待病毒表达21 d后，注射空载病毒小鼠（n=6）为空载病毒+氯氮平-N-氧化物（CNO）+电针组（mCherry+CNO+EA），随机选3只注射激活病毒小鼠用于脑片膜片钳验证病毒功能，剩余小鼠随机分为2组（n=6）:激活病毒+CNO+电针组（hM3D+CNO+EA）、激活病毒+盐水+电针组（hM3D+saline+EA），各组均电针“内关”“间使”，每日1次，共15 d。干预结束后，以Morris水迷宫、新物体识别实验评估小鼠学习记忆能力，EB染色法检测小鼠脑组织BBB通透性，免疫荧光染色法检测小鼠LC中TH/c-Fos、TH/NE共定位表达情况。结果: （1）与对照组相比，模型组小鼠学习记忆能力显著降低（P<0.01），海马Occludin、Claudin-5和ZO-1蛋白表达明显减少（P<0.01），NTS与LC中TH/c-Fos共定位表达、LC中TH/NE共定位表达明显增多（P<0.01）。与模型组相比，电针组小鼠学习记忆能力提高（P<0.05，P<0.01），海马Occludin、Claudin-5和ZO-1蛋白表达明显增加（P<0.01），NTS与LC中TH/c-Fos共定位表达、LC中TH/NE共定位表达减少（P<0.01，P<0.05）。（2）通过逆行示踪病毒证明，NTS中TH神经元可以投射到LC。（3）与mCherry+CNO+EA组和hM3D+saline+EA组相比，hM3D+CNO+EA组小鼠学习记忆能力显著降低（P<0.01），脑组织EB含量，LC中TH/c-Fos共定位表达、TH/NE共定位表达明显增多（P<0.01）。结论: 电针“内关”“间使”能改善AD小鼠BBB损伤及学习记忆功能障碍，其作用机制可能与抑制NTSTH-LC神经环路的激活有关。.
Bipolar disorder (BD) is a chronic and severe mental disorder with a high risk for recurrence, requiring long-term mood stabilization treatment approaches. The hazards of recurrence in BD include illness progression, decreasing treatment response, chronicity, comorbidity, suicidality, increased health service utilization, and greater direct and indirect economic costs. Treatment nonadherence is one of the most common modifiable deficiencies in the maintenance treatment of BD, which exacerbates the risk of recurrence and unfavorable course and outcome. Aripiprazole is the only dopamine partial agonist that is FDA-approved in a long-acting injectable (LAI) formulation for the maintenance treatment of adults with bipolar I disorder (BD-I), offered as both a once-monthly and bimonthly monohydrate. Herein, we synthesize the results supporting the efficacy, safety, and tolerability of both aripiprazole LAI formulations in BD-I. A narrative search was conducted by an expert opinion in the field, as well as targeted bibliographic searching. Both aripiprazole LAI formulations were established as efficacious in the reduction of manic and mixed episodes in adults with BD-I; however, their efficacy for bipolar depression prevention remains unproven. Aripiprazole LAI is well tolerated and safe, with injection site pain, sedation, weight increase, and akathisia being the most common adverse events. What is this summary about?Aripiprazole is a drug used to treat several mental health disorders, including schizophrenia and bipolar I disorder. It is offered in an oral tablet form taken daily or, more recently, via injections administered monthly or once every two months (bimonthly). What makes the injectable version different? How does it benefit patients compared to the oral tablets or other medications used to treat patients with bipolar I disorder? This paper aims to evaluate studies that have sought to answer these questions.What were the results?Our data indicate that aripiprazole long-acting injectables taken both monthly and bimonthly are safe and effective during the maintenance treatment of adults with bipolar I disorder. Discussions about the benefits and risks of aripiprazole injectables may take place at any point in the patient journey and at any phase of the illness. This includes newly diagnosed patients as well as patients who have already established a mutually agreed-upon plan of taking oral medication.What do the results mean?Aripiprazole long-acting injectables (monthly and bimonthly forms) are important treatment options of the maintenance treatment of bipolar I disorder. They serve as alternatives to daily oral administrations and may be discussed as part of shared decision-making. Descriptive data indicate that shared decision-making enhances satisfaction of healthcare. Therefore, these long-acting injectables could be a topic of consideration between the healthcare provider and the patient at any point throughout the illness journey.
Human visual motion processing is thought to involve two stages: local motion processing and global pooling of local motion signals. We used an efficient equivalent noise paradigm to explore temporal aspects of motion processing, specifically manipulating the lifetime of moving elements and overall stimulus-duration, to examine (respectively) local and global processing. Participants judged whether the overall direction of a dot pattern was clockwise or anti-clockwise of a reference direction. An adaptive staircase determined a) the minimum direction offset required for reliable judgment of direction when dots moved in a similar direction and b) the maximum directional noise (range of directions) that still allowed participants to tell if a stimulus was moving either ±45° from the reference direction. The two sets of thresholds allowed us to infer both a) the precision of participants' judgment of the direction of a single dot (i.e., local noise) and b) the number of samples they were effectively averaging (i.e., global sampling). Dots moved at 10 deg/s and we tested various dot lifetimes (33.36, 66.72, 133.4, and 266.8 ms) with a stimulus-duration of 1,000 ms, and various stimulus-durations (62, 125, 250, 500, 1,000, and 2,000 ms) with a dot lifetime of 133.4 ms. Longer element-lifetimes increased local directional precision but did not influence global integration (number of samples effectively averaged). Conversely, longer exposures did not greatly influence local precision, but increased global averaging by an average of 13% for every doubling of stimulus-duration. Thus, element-lifetime and stimulus-duration have dissociable effects on motion perception improving local and global motion processing, respectively.
Post-traumatic stress disorder (PTSD) remains a significant and often refractory mental health condition. Hyperbaric oxygen (HBO) therapy has demonstrated promise in alleviating symptoms of PTSD but optimal dosing and treatment duration remain unclear. To evaluate the clinical efficacy and dosing effects of two HBO protocols in patients with PTSD. We conducted a randomized controlled trial comparing two HBO protocols: 60 daily sessions of 90 minutes at either 2.0 atmospheres absolute (ATA) or 2.5 ATA (HBO15). Adults with severe PTSD (Clinician Administered PTSD Score [CAPS]-5 ≥ 33) were randomized to treatment arms. CAPS-5 scores were recorded every 2 weeks. Secondary outcomes include measures of depression, sleep, executive function, and safety. Preliminary results are presented for the first nine patients who completed therapy (HBO10: n=5; HBO15: n=4). Participants in HBO15 were younger (mean age 39 vs. 59 years, P = 0.2). Baseline PTSD severity (CAPS-5) was higher in HBO15 (median 61.5 vs. 48.0, P = 0.4). Other baseline psychological scores were similar between groups. Mean CAPS-5 improvement (ΔCAPS) was greater in HBO15 (-14.0 ± 21.2) vs. HBO10 (-5.3 ± 19.6), although not statistically significant (P = 0.8). Both groups demonstrated the largest symptom reduction by weeks 6-8, with a plateau observed thereafter despite continued treatment through week 12. Preliminary data suggest both HBO protocols are associated with symptomatic improvement in PTSD, with a trend toward greater effect in the higher-pressure group (2.5 ATA). Improvements appear to peak around 6-8 weeks, potentially indicating a shorter optimal treatment duration.
Background/Objectives: Delirium is a frequent and clinically significant complication in cardiac surgery patients and is associated with prolonged mechanical ventilation, longer Intensive Care Unit (ICU) stay, increased mortality, and long-term cognitive impairment. However, evidence regarding perioperative factors associated with delirium occurrence in cardiac surgery ICU patients remains limited. This study aims to investigate clinical factors associated with postoperative delirium in cardiac surgery patients admitted to the ICU. Methods: A single-center, prospective, observational study was conducted in a 14-bed cardiothoracic ICU in central Italy. Consecutively enrolled adult patients undergoing cardiac surgery were assessed for delirium using the Italian-validated Intensive Care Delirium Screening Checklist (ICDSC) every eight hours for five days. Univariate analysis and multivariate logistic regression were performed to identify factors associated with delirium occurrence. Results: A total of 175 patients were included, and delirium occurred in 44.6%. In the univariate analysis, patients with delirium presented significantly longer mechanical ventilation (10.5 vs. 8.0 h; p = 0.04) and higher APACHE II scores (p = 0.01). In the multivariable analysis, lower Glasgow Coma Scale (GCS) scores were independently associated with delirium occurrence (OR = 0.84; 95% CI: 0.71-0.99; p = 0.04). Urgent admission (OR = 2.02; p = 0.06) and mean arterial pressure (OR = 0.97; p = 0.08) did not reach statistical significance in the multivariable model. Conclusions: Delirium is highly prevalent after cardiac surgery. Lower postoperative GCS scores may represent an early marker of postoperative neurological vulnerability associated with delirium occurrence. Further multicenter studies are warranted to improve delirium risk stratification and clarify the mechanisms underlying postoperative cognitive dysfunction.
To compare response (reduction in headache frequency and differences in patient-reported outcomes) between Erenumab and OnabotulinumtoxinA from two phase-IV trials after 6 months of treatment. A prospective cohort study included two parallel cohorts of chronic migraine patients treated with either Erenumab 140 mg/month or OnabotulinumtoxinA 195 U every 3 months. Participants had no additional preventive therapies or comorbid psychiatric or chronic pain conditions. Baseline data collected included demographics, monthly headache (MHD) and migraine days (MMD), impact scales (MIDAS, HIT-6, MSQ), and anxiety/depression scores (BAI, BDI-II). Assessments were repeated at 6 months. Baseline characteristics were balanced. Efficacy analysis (measured by reduction in MHD/MMD and impact scales) was conducted using paired t-test, and linear regression models compared treatment-related changes between groups. A total of 114 patients were analyzed (57 per group), with no significant baseline differences. Both treatments produced significant reductions in headache frequency at 6 months (Erenumab: -7.93 MHD and -5.36 MMD, p < 0.001; OnabotA: -6.00 MHD and -4.31 MMD, p < 0.001), without statistically significant differences between therapies. Significant improvements were observed in HIT-6 and MSQ scores in both cohorts (p < 0.05). The Erenumab group showed significant reductions in MIDAS, BDI, and BAI scores (p < 0.05). Differences between treatments were significant for MIDAS improvements at three and 6 months (p < 0.05). Erenumab and OnabotulinumtoxinA are effective preventive treatments for chronic migraine. No significant differences were found in the magnitude of headache reduction at 3 or 6 months when comparing both treatments.
Meniscus injuries are one of the most common orthopedic pathologies. Arthroscopic partial meniscectomy can be performed if the injury has failed nonoperative management or is irreparable. Socioeconomic disparities within health insurance coverage have been known to hinder access to surgical intervention. The purpose of this study is to examine the impact of insurance status and socioeconomic demographics on the timeliness of care for meniscus tears in a high-volume urban safety-net hospital. A retrospective review was conducted of patients aged 18 or older who underwent partial meniscectomy at a single center between January 2018 and December 2022. Patients were categorized based on insurance status. Demographic data, clinical timeliness, and non-operative treatments were analyzed. Insurance groups were compared between key time intervals, including injury-to-diagnosis, injury-to-decision, diagnosis-to-decision, decision-to-procedure, and total injury-to-surgery duration. Chi-square and multivariate regression analyses assessed the relationship between insurance type and delays in care. Publicly insured patients composed 67% of the 288 patients. Public insurance patients were predominantly Black (48%) and Hispanic (32%) compared to private insurance patients, where Black and Hispanic patients constituted 33% and 10%, respectively. Public insurance patients experienced significantly longer injury-to-diagnosis intervals, averaging 115 days more than private insurance patients. Delays persisted at every stage of care, with public insurance patients demonstrating longer injury-to-decision and decision-to-procedure intervals. No significant differences were found in pre-operative management, including physical therapy and bracing. White race was an independent predictor of delays in diagnosis, surgical decision, and procedure time. Male sex had quicker diagnosis to decision times. This study demonstrates significant disparities in the timeliness of surgical care for meniscus tears, with public insurance status and minority race, mainly Black and Hispanic, serving as key predictors of care delays. Public insurance patients faced prolonged intervals across all stages of care, including a 115-day delay from injury to diagnosis. Structural inefficiencies, such as lower reimbursement rates and administrative complexity of public insurance programs, combined with patient-specific barriers like financial instability and mistrust, contribute to these delays. These findings underscore the need for systemic reforms to improve equity in healthcare access.
Fabry disease, an X-linked lysosomal storage disorder, can present with mixed ventilatory dysfunction on pulmonary function testing. In patients with a smoking history, this finding may trigger a reflexive consideration of COPD and unnecessary bronchodilator use. We report a case where bronchodilators were briefly used following the diagnosis of Fabry disease, highlighting the clinical inertia that persists even after a definitive diagnosis. A 39-year-old male with a 20-pack-year smoking history was diagnosed with Fabry disease through family cascade screening (α-galactosidase A activity: 4.93 nmol/L; plasma lyso-Gb3: 328.92 nmol/L; hemizygous GLA variant). Multisystem evaluation revealed mixed ventilatory dysfunction (FEV1/FVC 54.59%) without respiratory symptoms, left ventricular hypertrophy (septum 14-17 mm, posterior wall 15 mm), proteinuria (1.01 g/24 h), and corneal verticillata. Chest CT showed no emphysema. During hospitalization, inhaled budesonide plus ipratropium bromide (a bronchodilator) was briefly administered. However, recognizing that the ventilatory dysfunction was a manifestation of Fabry disease itself rather than COPD, the patient was discharged without a bronchodilator prescription. Enzyme replacement therapy (ERT) with agalsidase alfa (0.2 mg/kg every 2 weeks) was initiated as long-term disease-modifying treatment. Even after Fabry disease is confirmed, the presence of a smoking history and abnormal spirometry can trigger reflexive bronchodilator use, illustrating powerful clinical inertia. Respiratory physicians should strictly adhere to COPD diagnostic criteria. Once Fabry disease is diagnosed, ERT should be prioritized as the disease-modifying therapy, and bronchodilators, if used at all, should be reserved for symptomatic patients as an adjunct, not a substitute.
To observe the effect of electroacupuncture (EA) at "Zusanli" (ST36) on amyotrophic lateral sclerosis (ALS) in mouse models based on myeloid cell trigger receptor 2 (TREM2)-mediated microglial activation. Thirty-six SPF-grade male human mutant superoxide dismutase 1 (SOD1-G93A) transgenic mice were divided into a model group, an EA group, and a drug group, 12 mice in each group. Besides, 12 wide-type littermates were collected as a control group. In the EA group, EA was performed at the "Zusanli" (ST36), with an intermittent wave, at the frequency of 15 Hz, and for 10 min each intervention; once every other day, 3 interventions a week and for 4 continuous weeks. In the drug group, the intragastric administration of riluzole solution was given at 8 mg/kg, once daily, for 4 continuous weeks. After intervention completion, behavioral assessment of mice was conducted using rotarod test and wire hang test. With HE and Nissl staining adopted, morphology of motor neurons in the anterior horn of the spinal cord was observed. Immunofluorescence was used to detect the fluorescence intensity of TREM2 in the anterior horn of spinal cord. Western blot analysis was performed to measure the protein expression of interleukin (IL)-1β, γ interferon (IFN-γ), IL-4 and IL-10 in spinal cord tissue. Flow cytometry was used to analyze the proportion of CD86+ and CD206+ in spinal cord monocyte suspension. Compared with the control group, in the model group, motor neurons in the anterior horn of the spinal cord exhibited disordered arrangement; accompanied by nuclear pyknosis and cytoplasmic shrinkage; the latency to fall in the rotarod test and the cut-off time in the wire hang test were shortened, fluorescence intensity of TREM2 in the spinal anterior horn, the protein expression of IL-1β, IFN-γ, IL-4, and IL-10, and the proportion of CD86+ and CD206+ in spinal cord tissue increased(P<0.01). When compared with the model group, in the EA and drug groups, motor neurons in the anterior horn of the spinal cord were arranged regularly; nuclear pyknosis and chromatolysis were attenuated, and the structural integrity of neurons was improved; the latency to fall and the the cut-off time were prolonged, fluorescence intensity of TREM2 in the spinal anterior horn was reduced, the protein expression of IL-1β and IFN-γ decreased, and that of IL-4, and IL-10 increased in the spinal cord tissue; the proportion of CD86+ in spinal cord tissue was reduced and that of CD206+ elevated(P<0.01, P<0.05). Compared with the drug group, the EA group showed the increase of protein expression of IL-1β,and the decrease of IL-4, IL-10 in the spinal cord tissue and the proportion of CD206+ (P<0.05). Electroacupuncture at "Zusanli" (ST36) exhibits a certain improvements in motor function of SOD1-G93A transgenic mice. The underlying mechanism may be related to attenuating neuroinflammation via the modulation of microglial activation mediated by TREM2. 目的：基于髓样细胞触发受体2（TREM2）介导的小胶质细胞活化观察电针“足三里”对肌萎缩侧索硬化症模型小鼠神经炎症的影响。 方法：将36只SPF级雄性人突变型超氧化物歧化酶1（SOD1-G93A）转基因小鼠随机分为模型组、电针组、药物组，每组12只；选取12只同窝野生小鼠作为对照组。电针组于“足三里”进行电针干预，采用断续波，频率15 Hz，每次10 min，隔日1次，每周3次，共4周；药物组予利鲁唑溶液（8 mg/kg）灌胃，每日1次，共4周。干预结束后，应用转棒测试与钢丝悬挂测试评估各组小鼠行为学，HE染色和尼氏染色观察各组小鼠脊髓前角运动神经元形态，免疫荧光法检测各组小鼠脊髓前角TREM2荧光强度，Western blot法检测各组小鼠脊髓组织白细胞介素（IL）-1β、γ干扰素（IFN-γ）、IL-4、IL-10蛋白表达，流式细胞术检测各组小鼠脊髓组织单细胞悬液CD86+和CD206+细胞比例。 结果：与对照组比较，模型组小鼠脊髓前角运动神经元排列紊乱，出现核固缩、胞体皱缩等现象；转棒测试潜伏期和钢丝悬挂测试掉落时间缩短，脊髓前角TREM2荧光强度升高，脊髓组织IL-1β、IFN-γ、IL-4、IL-10蛋白表达升高，脊髓组织单细胞悬液CD86+、CD206+细胞比例升高（P<0.01）。与模型组比较，电针组和药物组小鼠脊髓前角运动神经元排列较规整，核固缩及尼氏小体溶解丢失现象改善，神经元结构完整性提高；转棒测试潜伏期和钢丝悬挂测试掉落时间延长，脊髓前角TREM2荧光强度降低，脊髓组织IL-1β、IFN-γ蛋白表达降低，IL-4、IL-10蛋白表达升高，脊髓组织CD86+细胞比例降低，CD206+细胞比例升高（P<0.01，P<0.05）。与药物组比较，电针组脊髓组织IL-1β蛋白表达升高，IL-4、IL-10蛋白表达降低，CD206+细胞比例降低（P<0.05）。 结论：电针“足三里”对SOD1-G93A转基因小鼠运动功能具有一定的改善作用，其作用机制可能为调控TREM2介导的小胶质细胞活化，进而改善神经炎症。.
Leptospirosis is a zoonotic disease caused by spirochete bacteria of the genus Leptospira, with a wide global distribution. In Ecuador, leptospirosis is endemic, particularly in low-resource tropical areas, and multiple animal reservoirs have been identified either in rural or urban areas, including stray dogs. In this study, a total of 81 domestic dogs presenting clinical manifestations compatible with leptospirosis were recruited at the Municipal Center for Animal Welfare in Guayaquil, Ecuador, in 2023. A survey regarding clinical, demographic, and environmental risk factors was filled in by every dog's owner; urine and blood samples were collected for pathogenic Leptospira diagnosis by qPCR for lipL32, rrs, and secY gene targets. A very high (62.96%) positivity rate for Leptospira infection was found. Almost 90% of the dogs were not vaccinated against Leptospira. Although the animals exhibited multiple clinical signs, none showed a statistically significant association with Leptospira positivity, confirming the nonspecific presentation of the disease and its potential for misdiagnosis. The consumption of bulk food emerged as a significant environmental risk factor only in the multivariate logistic regression and not in the univariate analysis, suggesting the need for improved food safety practices. Moreover, we reported very frequent close-contact behaviors between owners and dogs. Overall, our study underscores the potential role of owned urban dogs as reservoirs of Leptospira in the city of Guayaquil in Ecuador, emphasizing the need for public health policies to increase awareness and improve diagnosis in domestic animals under a comprehensive One Health vision.
In clinical research, bias is a systematic error that creates a difference between observed and true values. The increasing use of large datasets and artificial intelligence (AI) in medicine necessitates a renewed focus on how such errors can be introduced and propagated.This educational primer provides a consolidated framework of the three primary types of bias selection, information, and confounding/analytical. We synthesize these concepts for an interdisciplinary audience of clinicians and data scientists, using illustrative examples from both traditional clinical trials and modern, data-intensive research. Bias can arise at every stage of the research lifecycle: design, conduct, analysis, reporting, and dissemination. We illustrate how classic issues, such as selection bias (systematic differences between those included and those eligible/targeted, thus distorting effect estimates), manifest in data and how modern analytical methods can introduce novel forms of error if not carefully managed. A shared understanding of bias is essential for effective collaboration between clinical and data science teams. This primer offers a practical conceptual map to help these teams proactively identify, mitigate, and transparently report on potential sources of bias, ultimately fostering more robust and equitable clinical evidence.
Atrial fibrillation (AF) is the most common arrhythmia worldwide and is associated with significant morbidity and mortality. Catheter ablation of AF has been shown to result in a significant reduction in AF burden and recurrence. Pulsed field ablation (PFA) is a new modality of catheter ablation that is noninferior to its thermal ablation counterparts, coupled with a more favorable safety profile. This study seeks to compare clinical outcomes between two PFA systems: PulseSelect™ (Medtronic, Minneapolis, MN, USA) (circular catheter) and FARAPULSE™ (Boston Scientific, Marlborough, MA, USA) (pentaspline catheter). Secondary aims are to evaluate the impacts of post-ablation mapping with a high-density mapping catheter (PAHDMC) and both procedure and fluoroscopy times on recurrence. Overall, across 895 patients with a median follow-up of 12.5 months, there was a recurrence rate of 39%. PFA system, PAHDMC, and procedure time all had no effect on recurrence. To our knowledge, this is the first study to compare recurrence rates between different PFA systems. Fluoroscopy time, however, was a significant predictor of recurrence. In the pentaspline catheter group, the odds of recurrence were 60% greater for every 15 min increase in fluoroscopy time. Future studies are needed to continue comparing outcomes amongst PFA systems and assess whether PAHDMC improves outcomes in PFAs.
Cyanobacterial toxins (cyanotoxins) threaten aquatic ecosystems and human health, yet the factors influencing their production and distribution in freshwater remain unclear. In north-central Tennessee, nutrient-rich runoff from agricultural and urban areas, combined with a karst landscape that supports drinking and recreational water use, heightens the need to understand cyanotoxin behavior. To examine cyanotoxin patterns, the U.S. Geological Survey and the Tennessee Department of Environment and Conservation monitored 18 sites, including two wells under the influence of surface water, every two weeks from September 2022 to November 2024. At least one cyanotoxin was detected at all sites, with the highest concentrations in deep reservoirs and lower levels in shallow systems. Most detections occurred during summer and fall, aligning with high temperatures and rapid-onset drought. Statistical analysis indicated that increased specific conductivity and pH raised the likelihood of detecting total microcystin, likely resulting from drought conditions and nutrient-laden runoff. Additionally, dissolved microcystin showed an inverse relationship with Cumberland River water levels, and principal component analysis showed that Secchi depth, chlorophyll a, pH, temperature, and conductivity explained most water quality variability. These results help increase understanding of cyanotoxin distribution and associated water quality conditions during detections to guide future freshwater cyanotoxin monitoring studies.
Background and objective It remains unclear whether atlas hypoplasia is causative of symptomatic cervical canal stenosis or represents an independent and unrelated finding. There have been few dedicated studies describing atlas hypoplasia, and the existing literature has focused almost entirely on Asian populations. Therefore, the aims of the current study were threefold. First, we aimed to characterize the differences in cervical foraminal sagittal measurements by race and sex. Second, we evaluated the impact of age on cervical sagittal diameter and assessed the relationship between atlas hypoplasia and subaxial canal stenosis. Finally, we investigated the relationship between dens size and canal stenosis. Methods This was a single-institution retrospective cohort study approved by the Institutional Review Board at the University of Rochester School of Medicine and Dentistry. An overarching patient cohort was created by selecting patients with a Current Procedural Terminology (CPT) code of 72125-7 (CT of the cervical spine) and an International Classification of Diseases, 9th Edition (ICD-9) code 723.0 (cervical myelopathy) between January 1, 2014, and December 31, 2014. A total of 851 patients fulfilled the inclusion criteria. Variables collected included demographic and radiographic data. The inner sagittal diameters (ISD) at every cervical spine level, including the atlas, were measured. The prevalence of atlas hypoplasia was compared by age group. The correlation between each ISD was calculated. Among cases of atlas hypoplasia, the proportion of patients with subaxial canal stenosis was investigated. Results A total of 851 patients were included in the analysis. The mean ISD of the atlas was 31.4 ± 2.2 mm, and we defined atlas hypoplasia as an atlas ISD ≤ 27.0 mm. The mean space available for the cord (SAC) of the atlas was 19.0 ± 2.0 mm (range: 12.8-27.1). There was no significant difference in either the ISD of the atlas or the prevalence of atlas hypoplasia between the age groups. Pearson's correlation analysis showed that the ISD of the atlas had a strong correlation with the SAC of the atlas (r = 0.86, p < 0.01); a moderate correlation with both the sagittal diameter of the dens (coefficient = 0.48, p < 0.01) and the ISD of C2 (r = 0.59, p < 0.01) to C3 (r = 0.44, p < 0.01); and a weak correlation with the ISD of C4 (r = 0.37, p < 0.01), C5 (r = 0.38, p < 0.01), C6 (r = 0.36, p < 0.01), and C7 (r = 0.37, p < 0.01). A sub-cohort analysis of the 17 cases of atlas hypoplasia revealed that the mean ISD of the atlas was 26.3 ± 0.7 mm, and the mean SAC of the atlas was 14.5 ± 0.8 mm within this cohort. Regarding the rate of canal stenosis, the atlantal SAC was less than 14 mm in 17.6% of the cases, and the ISD of C2 to C7 was < 12 mm in 0%, 35.3%, 41.2%, 64.7%, 52.9%, and 47.1% of the cases, respectively. Conclusions The prevalence of atlas hypoplasia was not correlated with older age, which differs from subaxial developmental canal stenosis. Furthermore, although there was no strong correlation between the ISD of the atlas and each subaxial ISD, cases with atlas hypoplasia often involved subaxial canal stenosis.
Chronic lung allograft dysfunction significantly impairs long-term lung transplant survival. Bronchiolitis obliterans syndrome is a chronic lung allograft dysfunction phenotype characterized by fibroproliferative changes in noncartilaginous airways. We previously demonstrated that the tyrosine kinase inhibitor nintedanib reduces chronic airway changes in murine tracheal allografts. In this study, we investigated whether delayed treatment, similar to the clinical scenario following lung transplantation, would still be beneficial. Recipient CBA/JRj mice received orthotopic tracheal transplants from donor C57BL/6JRj mice. A dosage of 60 mg/kg of nintedanib was administered orally to transplanted mice every day between days 14 and 29 after transplantation. Histological and immunofluorescence analyses, as well as intragraft gene expression measurements, were performed after 14 and 30 d. Delayed-treated tracheal allografts (nintedanib 14-30) exhibited less evidence of chronic rejection than untreated allografts on day 30 (control 30). This is demonstrated by an increased epithelium-to-lamina propria ratio (0.62 ± 0.16 [nintedanib 14-30] versus 0.50 ± 0.01 [control 30]; P < 0.05), with a reduction in CD4+ T cell, dendritic cell, and macrophage infiltration. Furthermore, intragraft gene expression of inflammatory cytokines, adhesion molecules, and growth factors was also lowered. While allografts treated immediately (nintedanib 30) demonstrated a comparable epithelium-to-lamina propria ratio to the nintedanib 14-30 group, earlier treatment resulted in considerably lower infiltration of CD4+ and CD8+ T cells as well as alpha smooth muscle actin expression. Even delayed nintedanib therapy has an attenuating effect on chronic inflammation but is less effective regarding the fibroproliferative changes that are considered a sign of chronic airway changes after murine tracheal transplantation. Thus, it may serve as supportive therapy in the clinical setting after lung transplantation, but earlier initiation might be more effective.