bluuebunny/crossref_metadata_2025 huggingface dataset:
Short-term stability and night-to-night variability of sleep parameters in nightmares comorbid with chronic insomnia Disorder across multiple nights of polysomnography
Authors: Paquet Caitlin , Lenker Kristina P , Calhoun Susan L , Bixler Edward O , Vgontzas Alexandros N , Fernandez-Mendoza Julio
Published: February 2024

Study Objectives

The purpose of this study was to examine the degree of short-term stability of polysomnographic (PSG) measured sleep parameters and the overall differences between individuals with comorbid nightmares and insomnia compared to those with chronic insomnia disorder alone or good sleeping controls across four nights in the sleep lab.

Methods

A total of 142 good sleeping controls, 126 chronic insomnia alone, and 24 comorbid insomnia/nightmare participants underwent four consecutive nights of 8-hour PSG recordings. Outcomes included sleep continuity, architecture, and REM-related parameters across nights one through four. Intraclass correlation coefficients with mixed-effect variances and repeated-measure analysis of covariance were used, respectively, to determine short-term stability as well as between-participants and time-by-group interaction effects.

Results

Wake after sleep onset and stage 1 showed “poor stability” in the comorbid insomnia/nightmare group compared to “moderate stability” in the good sleeping controls and chronic insomnia alone group. Significant between-group effects (all ps < .05) showed that the comorbid insomnia/nightmare group took longer to fall asleep and had a greater first-night-effect in stage 1 compared to good sleeping controls and chronic insomnia alone group; in addition, the comorbid insomnia/nightmare and insomnia alone groups slept shorter, with fewer awakenings and REM periods, compared to the good sleeping controls.

Conclusions

Nightmares are associated with abnormal sleep above and beyond REM disruption, as sleep continuity was the primary aspect in which poor stability and group differences emerged. The greater inability to fall asleep and instability of sleep fragmentation in those with comorbid insomnia/nightmares compared to chronic insomnia alone may be attributed to the impact of presleep anticipatory anxiety and nightmare-related distress itself.

Clinical Trial Information

The data analyzed in this study does not come from any current or previous clinical trials. Therefore, there is no clinical trial information to report.
Neuropeptide substance P alters stem cell fate to aid wound healing and promote epidermal stratification through asymmetric stem cell divisions
Authors: Khalifa A , Xiao T , Abegaze B , Weisenberger T , Charruyer A , Sanad Samia , AbuElnasr Taher , Kashem S W , Fassett M , Ghadially R
Published: February 2024

Loss of sensory innervation delays wound healing and administration of the neuropeptide substance P improves re-epithelialization. Keratinocyte hyperproliferation post-wounding may result from symmetric stem cell (SC) self-renewal, asymmetric SC self-renewal, committed progenitor divisions, or a combination of these. However, the effects of sensory denervation and of neuropeptides on SC proliferation are not known. Here we show that early after wounding both asymmetric and symmetric SC self-renewal increase, without significant committed progenitor (CP) activation. Decreased sensory innervation is associated with a decrease in both SC and CP proliferation. Based on previous work showing that substance P is decreased in capsaicin-treated mice and improves wound healing in normal skin, we examined the effects of substance P on SC and CP proliferation during wound healing. Substance P restored asymmetric SC proliferation in skin with decreased sensory innervation, both at baseline and following wounding. Epidermis with decreased sensory innervation was severely thinned. Consistent with this, substance P-induced asymmetric SC proliferation resulted in increased stratification in skin with both normal and decreased innervation. Lapatinib prevented the substance P-induced increase in asymmetric SC divisions in murine epidermis, as well as the increase in epidermal stratification, suggesting that asymmetric SC divisions are required for epidermal stratification.
Effect of Fungicide and Timing of Application on Management of Phoma Black Stem of Cultivated Sunflowers in the United States
Authors: Hansen Bryan C. , Gilley Michelle A. , Berghuis Brandt G. , Halvorson Jessica M. , Friskop Andrew J. , Schatz Blaine G. , Kandel Herman J. , Fitterer Scott A. , Carruth David J. , Mathew Febina M. , Markell Samuel G.
Published: February 2024

Phoma black stem (PBS), caused by Phoma macdonaldii Boerema (teleomorph Leptosphaeria lindquistii Frezzi), is the most common stem disease of sunflower (Helianthus annuus L.) in the northern Great Plains region of the United States. However, the impact of PBS on sunflower yield in the United States is unclear, and a near complete absence of information on the impact of fungicides on disease management exists. The objectives of this study were to determine the impact of PBS on sunflower yield, the efficacy of available fungicides, the optimal fungicide application timing, and the economic viability of fungicides as a management tool. Fungicide timing efficacy was evaluated by applying single and/or sequential applications of pyraclostrobin fungicide at three sunflower growth stages in 10 field trials between 2017 and 2019. Efficacy of 10 fungicides from the Fungicide Resistance Action Committee (FRAC) groups 3, 7, and 11 were evaluated in four field trials between 2018 and 2019. The impact of treatments on PBS were evaluated by determination of incidence, severity, maximum lesion height, disease severity index (DSI), and harvested yield. Nine of the 10 fungicides evaluated and all fungicide timings that included an early bud application resulted in disease reductions when compared with the nontreated controls. The DSI was negatively correlated to sunflower yield in high-yield environments (P = 0.0004; R2 = 0.3425) but not in low- or moderate-yield environments. Although FRAC 7 fungicides were generally most efficacious, the sufficient efficacy and lower cost of FRAC 11 fungicides make them more economically viable in high-yielding environments at current market conditions.
Inpatient Management of Hyperemesis Gravidarum
Authors: Clark Shannon M. , Zhang Xue , Goncharov Daphne Arena
Published: February 2024

Hyperemesis gravidarum has a reported incidence of approximately 0.3–3% of pregnancies. Without treatment, refractory hyperemesis gravidarum can result in dehydration, electrolyte deficiencies, and severe nutritional deficiencies, resulting in significant maternal morbidity. The overall goals of inpatient management of refractory hyperemesis gravidarum are the resumption of oral intake to an adequate level to maintain hydration and nutrition, including the ability to tolerate oral pharmacotherapy. Patients initially are stabilized with rehydration and electrolyte repletion. There are numerous pharmacotherapeutics available that can be administered intravenously to control symptoms when oral intake is not an option. However, despite maximizing typical antiemetics, there will be cases refractory to these medications, and alternative pharmacotherapeutics and nutrition-support modalities must be considered. Mirtazapine, olanzapine, corticosteroids, and gabapentin are examples of alternative pharmacotherapeutics, and enteral and parenteral nutrition are alternative therapies that can be used when oral intake is not tolerated for prolonged time periods with ongoing weight loss. In refractory cases of hyperemesis gravidarum, the risks and benefits of these alternative forms of management must be considered, along with the risks of undertreated hyperemesis gravidarum and the overall effect of hyperemesis gravidarum on patients' quality of life.
Addressing Privacy Concerns Surrounding Oocyte Donation in the United States
Authors: Tsai Shelun , Eaton Jennifer L.
Published: February 2024

Oocyte donation has greatly expanded in the past several decades since the first procedure was performed in 1983. According to the Centers for Disease Control, the number of cycles using donor oocytes increased from 18,011 cycles in 2010 to 27,131 cycles in 2019. Oocyte donation has become an important reproductive option for women with diminished ovarian reserve, recurrent failed in vitro fertilization, or heritable genetic conditions. It is also particularly important for single men, same-sex male couples, and men with a transgender woman partner. More recently, societal changes accompanying the expansion of social media and broader access to direct-to-consumer DNA testing have raised concerns about privacy and anonymity. In this article, we review two specific aspects of donor privacy: privacy related to personal identifiers provided by clinics or donor egg bank websites and privacy related to direct-to-consumer genetic testing. We also provide clinical recommendations specific to the United States for working with oocyte donors and donor oocyte recipients.
Follow-up Value of Hip Medial Ultrasound in Infants and Children With Developmental Dysplasia of the Hip Treated With Reduction and Spica Casting
Authors: Yu Jingmiao , Chen Tao , Fu Gang , Lyu Xuemin , Wang Chao , Wang Yukun , Yang Zheng , Guo Wen
Published: February 2024

Objective:

Closed or open reduction and spica casting are common treatments for children aged 6 to 18 months, as well as infants aged 0 to 6 months whose harness treatment for developmental dysplasia of the hip (DDH) was unsuccessful. The study aimed to quantify the distance between the femoral head and the acetabulum after closed or open reduction and evaluate the dynamic docking progression of the femoral head using serial hip medical ultrasound.

Methods:

We retrospectively reviewed the medical records and hip medial ultrasound images of a consecutive series of patients with DDH who underwent spica casting after reduction and compared images obtained immediately after reduction and at follow-up. The first cast (stage I) was maintained for 2 to 3 months and scheduled for outpatient repeat ultrasound in 4 to 8 weeks. Then the second cast was placed (stage II), lasting for another 2 to 3 months. The triradiate cartilage-femoral head distance (TFD) was measured in the acetabulum coronal mid-sectional plane. The Wilcoxon signed-rank test was used to compare the TFD values.

Results:

This study included 49 patients. All patients underwent hip medial ultrasound 0 to 3 days after stage I (time 1) and 4 to 8 weeks (time 2) postoperatively, with 24 patients reviewed again 0 to 7 days after stage II. The TFD values in time 1 and time 2 were 6.0 (5.0, 9.0) mm and 5.0 (3.6, 7.0) mm, respectively. There was a statistically significant difference between times 1 and 2 regarding TFD values in 49 close-reduction hips (6.0 vs 5.0 mm, P < 0.001). Similar findings were also observed in 13 open-reduction hips (6.0 vs 5.0 mm, P = 0.023).

Conclusions:

Hip medial ultrasonography during the period of cast immobilization after reduction in children with DDH can objectively and quantitatively show the dynamic change of the distance between the femoral head and the acetabulum, and can be used to assess reduction of the hip and progression of femoral head docking.

Level of Evidence:

Level II—prognostic study.
Estimated Excess Deaths Due to COVID-19 Among the Urban Population of Mainland China, December 2022 to January 2023
Authors: Raphson Leon , Lipsitch Marc
Published: February 2024

Background:

Mainland China experienced a major surge in SARS-CoV-2 infections in December 2022–January 2023, but its impact on mortality was unclear given the underreporting of coronavirus disease 2019 deaths.

Methods:

Using obituary data from the Chinese Academy of Engineering (CAE), we estimated the excess death rate among senior CAE members by taking the difference between the observed rate of all-cause death in December 2022–January 2023 and the expected rate for the same months in 2017–2022, by age groups. We used this to extrapolate an estimate of the number of excess deaths in December 2022–January 2023 among urban dwellers in Mainland China.

Results:

In December 2022–January 2023, we estimated excess death rates of 0.94 per 100 persons (95% confidence interval [CI] = −0.54, 3.16) in CAE members aged 80–84 years, 3.95 (95% CI = 0.50, 7.84) in 85–89 years, 10.35 (95% CI = 3.59, 17.71) in 90–94 years, and 16.88 (95% CI = 0.00, 34.62) in 95 years and older. Using our baseline assumptions, this extrapolated to 917,000 (95% CI = 425,000, 1.45 million) excess deaths among urban dwellers in Mainland China, much higher than the 81,000 in-hospital deaths officially reported from 9 December 2022 to 30 January 2023.

Conclusions:

As in many jurisdictions, we estimate that the coronavirus disease 2019 pandemic had a much wider impact on mortality than what was officially documented in Mainland China.
One-stage Intraconal Volume Modification for Exposed and Nonexposed Ball Implants
Authors: Vahdani Kaveh , Rose Geoffrey E. , Marjanovic Branka , Verity David H.
Published: February 2024

Purpose:

To assess long-term outcomes and reinterventions for exposed and nonexposed intraconal orbital implants after single-stage socket revisional surgery.

Methods:

Retrospective case-note review of patients with exposed or nonexposed orbital ball implants, who underwent a single-stage ball exchange (Group I) or ball removal with dermis-fat graft (Group II); Group I was subdivided as having either exposed (A) or nonexposed (B) implants. Outcomes were compared with similar cohorts undergoing multistage surgery.

Results:

Of 172 patients (54% male), 153 (89%) underwent ball exchange (Group I) and 19 (11%) had dermis-fat graft (Group II). With a mean follow up of 7.8 years, Group I patients without ball exposure (Group IB) had a slightly higher rate of reintervention for persistent volume deficit (21% vs. 9%; p = 0.163) and implant migration (6% vs. 0%; p = 0.091), while Group IA patients—having surgery for exposed implants—had more reexposures (7% vs. 3%; p = 0.270). Single-stage and 2-stage surgery had similar reintervention rates, with the exception of a trend toward fewer volume enhancements for those with nonexposed implants (17% vs. 30%; p = 0.380), and a shorter time to (re)exposure for exposed implants after 2-stage procedures (mean 0.33 vs. 3.5 years; p = 0.571). Group II patients required further volume enhancement in 32% of 1-stage procedures, and one patient needed graft removal.

Conclusion:

Single-stage volume modification is effective and the results are comparable to staged surgery for either exposed or nonexposed implants. Most patients report a stable prosthesis and satisfactory cosmesis, after a faster rehabilitation.
Transcutaneous electric acupoint stimulation reduced consumption of profopol in patients undergoing laparoscopic surgery: A randomized clinical trial
Authors: Zhang Minjuan , Cairen Zhuoma , Liu Xiaoyu , Deng Jiao , Mu Xiaoxiao , Wang Yun , Lu Zhihong
Published: February 2024

Background:

Propofol is a common regimen for general anesthesia maintenance. But propofol can dose-dependently generate cardiopulmonary depression. Thus, any strategy to reduce propofol dosage during laparoscopic surgery may have underlying beneficial effect for patient prognosis. Previous studies indicated both analgesic and sedative effect of acupoint stimulation. However, its main sedative effect on patients under general anesthesia remains unclear.

Objective:

The aim of this study was to investigate the sedative effect of transcutaneous electrical acupoint stimulation (TEAS) on patients scheduled for laparoscopic surgery under general anesthesia.

Design, setting, participants and interventions:

In this randomized clinical trial, patients scheduled for laparoscopic surgery under general anesthesia in Xijing hospital were randomly assigned to 3 groups, receiving electrical stimulation at the Shenmen (HT7)/Ximen (PC4) (TEAS group), stimulation at the shoulder (non-acupoint group) or no stimulation (control group), respectively.

Main outcome measures:

One hundred sixty-two patients completed the study. The primary outcome was the consumption of propofol, and secondary outcomes included features of recovery after surgery, major complications after surgery and by 1 year after surgery.

Results:

In patients undergoing laparoscopic surgery, the doses of propofol decreased significantly in the TEAS group compared (0.10 ± 0.02 mg·kg−1·min−1) with the other 2 groups (both 0.12 ± 0.02 mg·kg−1·min−1, P < .001). The mean differences (95% confidence interval) for non-acupoint versus TEAS and control versus TEAS were 0.021 (0.012, 0.030) and 0.024 (0.013, 0.034), respectively. Time to awake and to extubation were not significantly different among the groups. The incidences of major complications after surgery and by 1 year after surgery were not significantly different among the groups.

Conclusion:

TEAS could induce additional sedative effect in patients during laparoscopic surgery and reduce propofol consumption.
Association between serum lactate, lactate clearance rate, and 30-day mortality among patients undergoing mechanical ventilation: A retrospective cohort study of MIMIC-III database
Authors: Sheng Bo , Li Shan , Wang He , Guo Zhe , Zhang Zhenyu
Published: February 2024

Serum lactate has been used as a prognostic indicator in intensive care unit patients, and however, the single lactate value may not be enough to reflect changes during illness conditions. Herein, this study aims to explore the association between serum lactate and lactate clearance rate and 30-day mortality in patients undergoing mechanical ventilation (MV). Demographic and clinical data of 2628 adults were extracted from the medical information mart for intensive care-III clinical database in this retrospective cohort study. The lactate clearance rate was calculated using the serum lactate at the beginning of MV (T0), and serum lactate at the12 hours after MV beginning (T1). Univariate and multivariate Cox regression analyses were used to screen covariates, and explore the association between serum lactate and lactate clearance rate and 30-day mortality. We also explored these associations in different T0 serum lactate level subgroups. The evaluation indexes were hazard ratios (HRs) and 95% CIs. In addition, receiver operator characteristic (ROC) curve with area under the curve (AUC) was used to reflect the predictive performance of serum lactate and lactate clearance rate on 30-day mortality. A total of 827 (31.47%) mechanically ventilated patients died within 30 days. After adjusting for covariates, elevated T0 (HR = 1.04, 95%CI: [1.02–1.07]) and T1 (HR = 1.07, 95%CI: [1.04–1.10]) serum lactate was both associated with an increased risk of 30-day mortality, while higher lactate clearance rate was negatively associated with the risk of 30-day mortality (HR = 0.64, 95%CI: [0.50–0.81]). Among patients with T0 lactate ≥2 mmol/L, T1 serum lactate ≥4 mmol/L was associated with an increased risk of 30-day mortality, while lactate clearance rate ≥50 was associated with a decreased risk (all P < .05). Moreover, T1 serum lactate had a potential predictive value on 30-day mortality with an AUC of 0.605. Serum lactate and lactate clearance rate were both associated with 30-day mortality in patients undergoing MV. Our results may provide some references for further studies to explore the roles of serum lactate and lactate clearance rate in prognoses of critical patients.
Cognitive and behavioral approaches to occupational stress management: The case of adult education administrative workers in Nigeria
Authors: Anyadike Nkechi , Ogiri Happiness Kodichinma , Agbo Solomon Uchenna , Osang Bessong Napoleon , Bessong Columbus Deku , Godwin Ozurumba Iheanyichukwu , Nkemjika Ogechi , Onyinye Ekere , Onyeodiri Imo Charity , Okengwu Mary , Nwabuko Linus Okechukwu , Otu Mkpoikanke Sunday , Victor-Aigbodion Vera , Ndille Roland
Published: February 2024

Background:

Those in administrative positions in adult education are more likely to suffer from stress because of the hard work they do, long hours in the office, a lack of adequate medical and welfare packages, and a lack of financial aid. In this study, adult education workers in Nigeria were assessed on the effectiveness of a cognitive and behavioral approach to managing occupational stress in public administration.

Method:

This study was a group-randomized trial in which 94 adult education workers occupy public administrative positions within Enugu State, Nigeria, participated. Data were collected using 2 instruments, the Perceived Stress Scale, and the Workplace Stress Scale, which were validated by cognitive and behavioral psychologists at the University of Nigeria, Nsukka. The instruments contained internal construct and content validity as determined by Cronbach alpha. ANCOVA was employed to test for hypotheses and answer research questions.

Results:

This study demonstrates that cognitive and behavioral approaches are significantly effective in managing occupational stress among adult education workers who work for public agencies.

Conclusion:

To improve stress management capacity among adults in public administration positions, researchers recommend frequent exposure to cognitive and behavioral approaches.
Presentation of glomerulocystic disease in a young onset diabetes: A case report
Authors: Huang Wen-Hung , Tu Kun-Hua , Chen Tai-Di , Weng Cheng-Hao , Hsu Ching-Wei
Published: February 2024

Rationale:

This case report presents a challenging medical scenario involving a young adult male who exhibited an unusual combination of symptoms, including abrupt weight loss, declining renal function, proteinuria, and concurrent onset of diabetes mellitus. Remarkably, the patient had no previous medical history or family history of similar conditions, necessitating a comprehensive investigation.

Patient Concerns:

On March 10, 2021, a 25-year-old male sought medical attention due to the aforementioned symptoms. Initial assessments revealed stage 5 chronic kidney disease, with elevated blood urea nitrogen (BUN) and serum creatinine (Cr) levels, as well as significant proteinuria. The only notable physical finding was obesity, and renal ultrasound showed normal-sized kidneys without cysts.

Diagnosis:

A treatment plan was initiated to stabilize creatinine levels, including medications such as Glimepiride, Glyxambi, Bisoprolol, Amlodipine, and Valsartan. However, despite diligent medication management, proteinuria persisted, prompting further evaluation. A renal biopsy was performed on April 12th, 2023, leading to the diagnosis of glomerulocystic kidney disease with early-stage changes indicative of diabetic nephropathy.

Interventions:

The patient continues to receive ongoing care and follow-up at our outpatient clinic to optimize therapeutic interventions and elucidate the underlying etiology of this complex clinical scenario.

Outcomes:

Ongoing investigations and therapeutic interventions are crucial to understand the underlying cause and optimize patient care in this intricate clinical scenario.

Lessons:

This case underscores the complexity of diagnosing and managing a young adult presenting with concurrent renal dysfunction, proteinuria, and diabetes mellitus in the absence of prior underlying conditions. It highlights the importance of comprehensive evaluation and ongoing care in such challenging cases.
Prevention and control of hospital-acquired infections with multidrug-resistant organism: A review
Authors: Ji Binghui , Ye Weijiang
Published: February 2024

Multidrug-resistant is defined as nonsusceptibility to at least 1 agent in 3 or more antimicrobial categories. Controlling the spread of drug-resistant organisms is a key step in the management of hospital-acquired infections (HAIs). To review the progress of research on the prevention and control of HAIs with multidrug-resistant organism (MDRO) in the past 5 years, and to provide reference for the development of comprehensive measures for the prevention and control of HAIs with MDRO. We conducted a search in the PUBMED database for studies related to MDRO and HAIs from 2018 to 2023, then integrated this data with information sourced from the U.S.A. The Centers for Disease Control and Prevention. Utilizing information technology to monitor and provide feedback on hand hygiene practices can enhance compliance. Environmental disinfection techniques such as ultraviolet or hydrogen peroxide demonstrate potential in reducing MDRO transmission. While some studies support that contact isolation measures for MDRO-infected or colonized patients can reduce HAIs, others do not confirm this outcome. Approaches for MDRO colonization among patients or physicians may mitigate MDRO transmission risk. Implementing clusterization interventions proves to enhance efficiency and cost-effectiveness in preventing and controlling MDRO. Early screening for pathogen species emerges as a valuable strategy aiding in antimicrobial use control. Combined with evidence from the literature, implementing clusterization interventions that include measures such as monitoring and feedback on hand hygiene and improved environmental disinfection techniques can help prevent and control HAIs with MDRO. However, further clinical studies are needed to validate the optimal clusterization intervention.
A case of digoxin intoxication caused by short-term massive overdose: Case report
Authors: Li Hua , Zhang Chun-hai , Liu Ming-wei
Published: February 2024

Rationale:

Digoxin is a frequently prescribed medication for the management of both acute and chronic cardiac insufficiency. The overdose ingestion of digoxin can result in a range of arrhythmias, with severe cases potentially leading to malignant arrhythmias and fatal outcomes. To date, there is a lack of documented cases related to acute digoxin intoxication resulting from the administration of massive digoxin overdose in the short term.

Patient concerns:

A 37-year-old female patient was admitted to the emergency department following a suicide attempt involving the administration of 330 tablets of digoxin (each tablet containing 0.25 mg). The patient exhibited symptoms of confusion, nausea, and vomiting for around 30 minutes. The patient had a history of depression.

Diagnoses:

The patient was diagnosed with digoxin intoxication.

Interventions:

The patient underwent many medical interventions including stomach lavage, administration of laxatives, correction of cardiac arrhythmias, provision of myocardial nutrition, diuresis, correction of acid-base balance, and management of electrolyte disturbances, among others.

Outcomes:

Following a treatment of 9 days, the patient exhibited no signs of discomfort, maintained consciousness, and the serum concentration of digoxin was indeterminable. Upon reevaluation of the electrocardiogram, it was determined that no arrhythmia was present. Consequently, the patient was authorized to be discharged from the hospital.

Conclusions:

There is currently no documented evidence of cases involving a significant overdose of digoxin resulting in intoxication. The patient had a comprehensive treatment regimen consisting of stomach lavage, administration of a laxative, correction of cardiac arrhythmias, provision of myocardial nutrition, fluid replacement, diuresis, and supportive therapy, resulting in successful outcomes.

Lessons:

There have been no known cases of intoxication resulting from a significant overdose of digoxin, specifically with the consumption of 330 tablets (0.25 mg/tablet). However, in the event of ingesting excessive amounts of digoxin, it is imperative to promptly administer stomach lavage, administration of a laxative, and arrhythmia correction. The administration of temporary pacemaker therapy is recommended for patients presenting with high atrioventricular block, whereas hemoperfusion is advised for patients with renal insufficiency as a means to eliminate digoxin from the body.
The Dilator-Dotter technique can successfully treat tandem lesions of posterior circulation
Authors: Han Ning , Ma Liang , Zhao Lei , Xu Guodong , Jia Yangjuan , Wang Hebo
Published: February 2024

In this study, we applied the Dilator-Dotter technique, a catheter-based angioplasty, to cross through severely stenotic or occluded vertebral arteries during mechanical thrombectomy, and we explored its efficacy and safety in treating tandem lesions of posterior circulation. We performed a retrospective analysis of patients with acute stroke caused by tandem lesions of posterior circulation treated with the Dilator-Dotter technique and thrombectomy between July 2017 and December 2021. In addition to collecting clinical, radiographic, and procedural data from patient records, we also collected information about surgical complications and outcome. We enrolled 9 patients for this study. In all cases, the vertebral artery (VA) on the affected side was crossed through via the Dilator-Dotter technique, and mechanical thrombectomy was successfully performed. The average time from groin puncture to revascularization (TICI 2B–3) was 26 minutes (range 16–50 minutes). Eight patients (89%) achieved complete recanalization with TICI 3, and only 1 patient suffered from thrombus escape to the posterior cerebral artery. Eight patients underwent VA stenting, while the remaining patient was excluded from this procedure because a postoperative brain CT scan recorded obvious staining of the contrast medium within the infarcted area. Five patients had modified Rankin Scale scores ≤ 3 at the 3-month follow-up examination, and 2 patients died due to postoperative cerebral hemorrhage and severe ischemia. The Dilator-Dotter technique may represent a safe and effective treatment for tandem lesions of posterior circulation. Using this method, the lesions can be rapidly recanalized and treated.
Gender and age differences in KDIGO treatment targets among people on maintenance hemodialysis: Findings from a tertiary hospital in Vietnam
Authors: Pham Hien Van , Tran Nhat Van , Thai Truc Thanh , Tran Huong Thi Bich
Published: February 2024

Age and gender are 2 important factors in the treatment of end-stage chronic kidney disease with hemodialysis. Understanding the influence of these 2 factors can help optimize treatment for this population. This study evaluated gender and age differences in achievement of Kidney Disease Improving Global Outcomes (KDIGO) treatment targets. A cross-sectional study was conducted on 324 chronic hemodialysis patients at a tertiary referral hospital in Ho Chi Minh City, Vietnam. KDIGO treatment targets included treatment time, prescribed Qb, treated blood volume, urea reduction ratio, spKt/V, hemoglobin, albumin, phosphorus, calcium, and parathyroid hormone. Men had significantly higher treatment time (P = .003), prescribed Qb (P = .037) and hemoglobin (P = .031) than women. However, women had significantly higher treated blood volume (P < .001), spKt/V (P < .001) and URR (P < .001). No significant difference between men and women was found in albumin, calcium, phosphorus, and parathyroid hormone. Based on KDIGO treatment targets, women had a significantly higher rate of achievement of spKt/V > 1.2 (91.4% vs 80.7%, P = .005) and URR ≥ 70% (77.0% vs 54.7%, P < .001) than men. A significantly higher rate of treated volume of ≥ 1 L/kg/BW, and phosphorus 2.5 to 4.6 mg/dL was found in women (90.0% and 40.2%) compared to men (68.7% and 27.3%). In contrast, men had a significantly higher rate of prescribed Qb ≥ 300 mL/min (26.7% vs 12.6%, P = .001), albumin ≥ 40 g/L (36.7% vs 26.4%, P = .047), and Hb > 12 g/dL (22.0% vs 11.5%, P = .011) than women. There was no significant difference between men and women in the rate of calcium 8.4 to 10.4 mg/dL, and parathyroid hormone 150 to 600 pg/mL. These differences were not the same across 4 age categories (<60, 60–69, 70–79, and ≥ 80). Most of the differences above were among patients aged < 60 and 60 to 69 years. Although men had higher satisfactory treatment parameters than women, based on KDIGO treatment targets, women received hemodialysis more effectively than men. Treatment targets for patients on hemodialysis should consider gender and age differences.
Common mechanisms of Wumei pills in treating ulcerative colitis and type 2 diabetes: Exploring an integrative approach through network pharmacology
Authors: Sun Chang , Xiao Keyuan , He Yinxiong , Li Xinghua
Published: February 2024

Wumei pills (WMP), a classical Chinese herbal formula, have shown efficacy in the treatment of ulcerative colitis (UC) and type 2 diabetes (T2DM). However, the underlying mechanisms by which WMP simultaneously targets these distinct diseases remain unclear. In this study, a network pharmacology approach was employed to unravel the potential molecular mechanisms of WMP in UC and T2DM treatment. This analysis provides a bioinformatics foundation for the traditional Chinese medicine concept of “treating different diseases with the same treatment.” WMP was found to contain 65 active components, including flavonoids, sterols, and alkaloids, that act on 228 shared targets for UC and T2DM. Network analysis identified 5 core compounds (Quercetin, Kaempferol, beta-Sitosterol, Isocorypalmine, Stigmasterol) and 8 core proteins (AKT1, ESR1, TP53, IL6, JUN, MYC, TNF, EGFR) that play pivotal roles in the treatment of UC and T2DM by WMP. WMP exerts its therapeutic effects by modulating signaling pathways, including the NF-κB pathway, PI3K-Akt pathway, and p53 pathway. Molecular docking results indicate a strong binding affinity between core compounds and core genes. This study bridges the understanding of 2 diseases using network pharmacology and provides insights into shared therapeutic mechanisms, opening doors for further research in modern Chinese herbal formulations.
Frequency of EMG abnormalities in idiopathic inflammatory myopathies under the EULAR/ACR classification criteria
Authors: Hokkoku Keiichi , Yamamoto Junpei , Uchida Yudai , Kondo Amuro , Mukai Taiji , Hatanaka Yuki , Kono Hajime , Shimizu Jun , Kobayashi Shunsuke , Sonoo Masahiro
Published: February 2024

The European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for idiopathic inflammatory myopathies (IIM) have been widely used in recent times. However, no studies have focused on electromyography (EMG) findings of IIM, considering the criteria. This study aimed to elucidate the frequency of EMG abnormalities, particularly fibrillation potentials and positive sharp waves (Fib/PSW), the most objective EMG findings of IIM. Clinical and EMG records of adult patients who were clinically diagnosed with polymyositis (PM), dermatomyositis (DM), amyopathic DM (ADM), or inclusion body myositis (IBM) were retrospectively reviewed and classified according to the EULAR/ACR classification criteria. The frequency of Fib/PSW in EMG was investigated in the recruited cases. Seventy-nine patients with clinically diagnosed IIM (44 with PM, 17 with DM, 7 with ADM, and 11 with IBM) were recruited. After classification using EULAR/ACR, 75 satisfied definite or probable IIM (61 and 14, respectively), and the frequency of Fib/PSW in this group was 95%. Furthermore, the remaining 4 patients with insufficient IIM probability also showed Fib/PSW. Fib/PSW may also be seen in cases with insufficient IIM probability not satisfying the criteria. EMG may help detect muscle involvement in these cases through Fib/PSW.
Cholera outbreaks among children in sub-Saharan Africa
Authors: Ubesie Agozie C. , Odimegwu Chioma L. , Ezeanolue Echezona Edozie
Published: February 2024

Purpose of review

We review current knowledge on the burden, impact and prevention of cholera among children who bear the brunt of cholera outbreaks in sub-Saharan Africa.

Recent findings

Several studies have shown that recent outbreaks of cholera among African children are related to minimal progress in basic sanitation and infrastructural development. Poor hygiene practices such as open defecation and indiscriminate disposal of feces are still common in many parts of Africa

Cholera case fatality rates in sub-Saharan Africa remain unacceptably high. Children are disproportionately affected and bear the brunt of the disease. Controlling outbreaks of cholera among African children will require a synchronous implementation of the five levels of disease prevention.
Morphologic and Molecular Heterogeneity of High-grade Serous Carcinoma Precursor Lesions
Authors: Chien Yen-Wei , Wang Yeh , Huang Peng , Lawson Barrett Craig , Kolin David L. , Chui M. Herman , Vang Russell , Numan Tricia A. , Soong T. Rinda , Wang Brant G. , Smith Saron Ann , Chen Chi-Long , Stone Rebecca , Douville Christopher , Wang Tian-Li , Shih Ie-Ming
Published: February 2024

Serous tubal intraepithelial carcinoma (STIC) is the fallopian tube precursor lesion for most cases of pelvic high-grade serous carcinoma (HGSC). To date, the morphologic, molecular, and clinical heterogeneity of STIC and a less atypical putative precursor lesion, termed serous tubal intraepithelial lesion, has not been well characterized. Better understanding of precursor heterogeneity could impact the clinical management of women with incidental STICs (without concurrent carcinoma) identified in cases of prophylactic or opportunistic salpingectomy. This study analyzed morphologic and molecular features of 171 STICs and 21 serous tubal intraepithelial lesions. We assessed their histologic features, Ki-67 and p53 staining patterns, and genome-wide DNA copy number alterations. We classified all precursor lesions into 2 morphologic subtypes, one with a flat surface (Flat) and the other characterized by budding, loosely adherent, or detached (BLAD) morphology. On the basis of pathology review by a panel of 8 gynecologic pathologists, we found 87 BLAD, 96 Flat, and 9 indeterminate lesions. As compared with Flat lesions, BLAD lesions were more frequently diagnostic of STIC (P<0.0001) and were found concurrently with HGSC (P<0.0001). BLAD morphology was also characterized by higher Ki-67 proliferation index (P<0.0001), presence of epithelial stratification (P<0.0001), and increased lymphocyte density (P<0.0001). BLAD lesions also exhibited more frequent DNA copy number gain/amplification at the CCNE1 or CMYC loci canonical to HGSCs (P<0.0001). Both BLAD morphology and STIC diagnoses are independent risk factors for an elevated Ki-67 proliferation index. No correlation was observed between BLAD and Flat lesions with respect to patient age, presence of germline BRCA1/2 mutation, or p53 staining pattern. These findings suggest that tubal precursor lesions are morphologically and molecularly heterogeneous, laying the foundation for further studies on the pathogenesis of HGSC initiation and identifying histologic features predictive of poor patient outcomes.
The Risks of First Onset Primary Hypertension Diagnosis in Thermal-Injured Patients
Authors: Efejuku Tsola A. , Wolf Steven E. , Song Juquan , Golovko Georgiy , El Ayadi Amina
Published: February 2024

INTRODUCTION

Hypertension (HTN) is a prevalent condition in the United States and leads to an increased risk of developing various comorbidities. However, the impact of new-onset hypertension following severe burns on patient outcomes is not known. We posit that hypertension onset after severe burn is associated with increased risk of developing comorbidities and mortality.

METHODS

Using the TriNetX database, burned patients diagnosed with essential hypertension after injury were compared to those who did not develop hypertension; neither had prior hypertension. Each cohort was grouped by sex, percent total body surface area (TBSA) burned, and age, then propensity-matched for sex, race, ethnicity, and lab values. Outcomes assessed were acute kidney injury (AKI), hyperglycemia, heart failure, myocardial infarction (MI), and death.

RESULTS

Those diagnosed with hypertension following severe burn were 4.9 times more likely to develop AKI, 3.6 times for hyperglycemia, 5.3 times for heart failure, 4.7 times for acute MI, and 1.5 times for mortality. Sex analysis shows that men were at greater risk for AKI (1.5 times), heart failure (1.1 times), and death (1.4 times). Women were 1.3 times more likely to develop hyperglycemia. Percent TBSA burned grouping showed increased risk for all outcomes with increasing severity. Age grouping indicated an elevated risk of developing AKI, heart failure, acute MI, and death.

CONCLUSION

New onset hypertension diagnosis in severely burned patients is associated with acute kidney injury, heart failure, acute MI, and death. Overall, males, older patients, and those with a higher % TBSA burned are at a higher risk of developing these comorbidities.
Toxin-based screening of C-terminal tags inEscherichia colireveals the exceptional potency of ssrA-like degrons
Authors: Beardslee Patrick C. , Schmitz Karl R.
Published: February 2024

All bacteria possess ATP-dependent proteases that destroy cytosolic proteins. These enzymes help cells mitigate proteotoxic stress, adapt to changing nutrient availability, regulate virulence phenotypes, and transition to pathogenic lifestyles. Moreover, ATP-dependent proteases have emerged as promising antibacterial and antivirulence targets in a variety of pathogens. The physiological roles of these proteases are largely defined by the complement of proteins that they degrade. Substrates are typically recognized in a highly selective manner, often via short unstructured sequences termed degrons. While a few degrons have been identified and rigorously characterized, we lack a systematic understanding of how proteases select valid degrons from the vast complexity of protein sequence space. Here, we describe a novel high-throughput screening approach inEscherichia colithat couples proteolysis of a protein toxin to cell survival. We used this method to screen a combinatorial library of C-terminal pentapeptide sequences for functionality as proteolytic degrons in wild typeE. coli, and in strains lacking components of the ClpXP and ClpAP proteases. By examining the competitive enrichment of sequences over time, we found that about one percent of pentapeptide tags lead to toxin proteolysis. Interestingly, the most enriched degrons were ClpXP-dependent and highly similar to the ssrA tag, one of the most extensively characterized degrons in bacteria. Among ssrA-like sequences, we observed that specific upstream residues correlate with successful recognition. The lack of diversity among strongly enriched sequences suggests that ssrA-like tags comprise a uniquely potent class of short C-terminal degron inE. coli. Efficient proteolysis of substrates lacking such degrons likely requires adaptors or multivalent interactions. These findings broaden our understanding of the constraints that shape the bacterial proteolytic landscape. Our screening approach may be broadly applicable to probing aspects of proteolytic substrate selection in other bacterial systems.
Early body weight gain in TALLYHO/JngJ mice predicts adult diabetic phenotype, mimicking childhood obesity
Authors: Hastreiter Sieglinde , Hoffmann Sandra , Richter Kerstin , Irmler Martin , Gerlini Raffaele , Fuchs Helmut , Gailus-Durner Valérie , Körner Antje , de Angelis Martin Hrabé , Beckers Johannes
Published: February 2024

Childhood obesity and type 2 diabetes are two emerging health issues worldwide. To analyze their underlying causes and develop prevention strategies, mouse models are urgently needed. We present novel insights into the polygenic TALLYHO/JngJ mouse model for diabetes. By precisely analyzing our original phenotypic data, we discovered that body weight at weaning age is the main predictor of the adult phenotype in TALLYHO/JngJ mice. The higher the weaning weight of male mice, the more likely they are to develop diabetes later in life. In contrast, a low weaning weight protected against the development of the diabetic phenotype in adults. In females, we found that high weaning body weights led to a constant higher body weight throughout life. We also showed that specifically the suckling period, rather than thein uteroperiod, is crucial for the development of the metabolic phenotype in later life. We observed an earlier onset of diabetes when the mice had higher body weights at weaning, aligning with metabolic histories observed in humans. Therefore, we recommend TALLYHO/JngJ mice as a model to investigate childhood obesity and to develop prevention strategies.

Highlights

The polygenic TALLYHO/JngJ mouse model is used to investigate type 2 diabetes, but the penetrance of the phenotype is highly variable.

We deeply analyzed our phenotype data and find that body weight at the age of weaning (BWW) is the main predictor for the obese and diabetic phenotype in TALLYHO/JngJ male mice later in life.

We suggest that TALLYHO/JngJ male mice are an excellent and urgently needed model to study childhood obesity.

Our data help the relevant scientific community to better control the penetrance of the diabetic phenotype in male TALLYHO/JngJ mice.
Average Nucleotide Identity basedStaphylococcus aureusstrain grouping allows identification of strain-specific genes in the pangenome
Authors: Raghuram Vishnu , Petit Robert A , Karol Zach , Mehta Rohan , Weissman Daniel B. , Read Timothy D.
Published: February 2024

Staphylococcus aureuscauses both hospital and community acquired infections in humans worldwide. Due to the high incidence of infectionS. aureusis also one of the most sampled and sequenced pathogens today, providing an outstanding resource to understand variation at the bacterial subspecies level. We processed and downsampled 83,383 publicS. aureusIllumina whole genome shotgun sequences and 1,263 complete genomes to produce 7,954 representative substrains. Pairwise comparison of core gene Average Nucleotide Identity (ANI) revealed a natural boundary of 99.5% that could be used to define 145 distinct strains within the species. We found that intermediate frequency genes in the pangenome (present in 10-95% of genomes) could be divided into those closely linked to strain background (“strain-concentrated”) and those highly variable within strains (“strain-diffuse”). Non-core genes had different patterns of chromosome location; notably, strain-diffuse associated with prophages, strain-concentrated with the vSaβ genome island and rare genes (<10% frequency) concentrated near the origin of replication. Antibiotic genes were enriched in the strain-diffuse class, while virulence genes were distributed between strain-diffuse, strain-concentrated, core and rare classes. This study shows how different patterns of gene movement help create strains as distinct subspecies entities and provide insight into the diverse histories of importantS. aureusfunctions.

Importance

We analyzed the genomic diversity ofStaphylococcus aureus, a globally prevalent bacterial species that causes serious infections in humans. Our goal was to build a genetic picture of the different strains ofS. aureusand which genes may be associated with them. We used a large public dataset (>84,000 genomes) that was re-processed and subsampled to remove redundancy. We found that individual genomes could be grouped into strains by sharing > 99.5% identical nucleotide sequence of the core part of their genome. We also showed that a portion of genes that are present in intermediate frequency in the species are strongly associated with some strains but completely absent from others, suggesting a role in strain-specificity. This work lays the foundation for understanding individual gene histories of theS. aureusspecies and also outlines strategies for processing large bacterial genomic datasets.