bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitigation of human iris angiogenesis through uPAR/LRP‐1 interaction antagonism in an organotypic ex vivo model
Authors: Pesce Noemi Anna , Plastino Flavia , Reyes‐Goya Claudia , Bernd Jonathan , Pavone Vincenzo , Dal Monte Massimo , Kvanta Anders , Locri Filippo , André Helder
Published: March 2024

Rubeosis Iridis (RI) is characterized by an increase in neovascularization and inflammation factors in the iris. During angiogenesis, the urokinase plasminogen activator (uPA) and its receptor (uPAR) play a pivotal role in extracellular matrix remodeling, where uPAR regulates endothelial cell migration and proliferation through assembly with transmembrane receptors. Here, in the context of hypoxia‐induced angiogenesis, the uPA/uPAR system blockage was investigated by using UPARANT in a novel ex vivo human iris organotypic angiogenesis assay. The effects of uPA/uPAR system antagonism in the humanized model of ocular pathologic angiogenesis were analyzed by sprouting angiogenesis and protein assays (western, dot blots, and co‐immunoprecipitation) and correlated to vascular endothelial growth factor (VEGF) inhibition. Phosphoprotein and co‐immunoprecipitation assay illustrated an unidentified antagonism of UPARANT in the interaction of uPAR with the low‐density lipoprotein receptor‐related protein‐1 (LRP‐1), resulting in inhibition of β‐catenin–mediated angiogenesis in this model. The effects of uPA/uPAR system inhibition were focal to endothelial cells ex vivo. Comparison between human iris endothelial cells and human retinal endothelial revealed an endothelial‐specific mechanism of β‐catenin–mediated angiogenesis inhibited by uPA/uPAR system blockage and not by VEGF inhibition. Collectively, these findings broaden the understanding of the effects of the uPA/uPAR system antagonism in the context of angiogenesis, revealing non‐canonical β‐catenin downstream effects mediated by LRP‐1/uPAR interaction.
Nursing Students’ Perceptions Regarding Teaching and Learning Practices That Promote Safe Medication Administration
Authors: Hnatyshyn Tammy , Ens Twyla , Estefan Andrew , Kirkpatrick Megan
Published: March 2024

This article reports on a study conducted to explore what helps and what complicates learning safe medication administration. In this study, nurse educators explored students’ perspectives on effective teaching practices, what influences medication errors and near misses, and strategies for improving students’ learning about medication administration. Students ranked nursing instructors, peers, and staff nurses as having the greatest positive impact on both their learning and patient safety. Good relationships, an appropriate pace of learning, and practice were also beneficial. Noise, time constraints, and interruptions were negatively associated with learning and patient safety.
Impact of Preoperative Aripiprazole on Postoperative Analgesia in Laparoscopic Hysterectomy
Authors: Alansary Amin Mohamed , Elbeialy Marwa Ahmed Khairy
Published: March 2024

Objectives:

Aripiprazole is a second-generation atypical antipsychotic with worldwide clinical approval. Nevertheless, its perioperative antinociceptive application has not been studied. As a result, the purpose of this study was to investigate the analgesic effects of perioperative aripiprazole on reducing postoperative pain, as well as the possible adverse effects.

Methods:

This randomized controlled study enrolled eighty female patients scheduled for laparoscopic hysterectomy who were assigned randomly into two equal groups in 1:1; Aripiprazole group (n=40): patients received an aripiprazole 30 mg tablet orally three hours before surgery, and Placebo group (n=40): patients received a placebo tablet three hours before surgery. The 24-hour morphine consumption postoperatively was the primary outcome, and the time to the first analgesic request, sedation scores, and the incidence of perioperative adverse events were the secondary outcomes.

Results:

The mean 24-hour morphine consumption was significantly lower with aripiprazole (2.5±0.5 mg) than with placebo (23.7±1.6 mg) (Mean±SE −21.2±0.3, 95% CI: −21.7 to −20.6, P<0.001). In addition, mean time to the first analgesic request was significantly longer with aripiprazole (212.2±14.7 min) than with placebo (27.0±2.0 min) (Mean±SE 185.2±2.3, 95% CI: 180.5 to 189.8, P<0.001). Furthermore, aripiprazole group reported higher sedation scores (P<0.001). Bradycardia and hypotension were reported more frequently among patients in the aripiprazole group (P<0.05).

Discussion:

Aripiprazole was effective in reducing pain following laparoscopic hysterectomy. Although self-limited, side effects should be taken into consideration when using the medication perioperatively.
Pediatric Spastic Wrist Contractures Can Be Well Managed With Wrist Arthrodesis
Authors: Cain Megan , Lemhouse Paige , Buckon Cathleen , Freese Krister P.
Published: March 2024

Background:

Severe spastic wrist contractures secondary to cerebral palsy (CP) or alike can have significant implications for patient hand function, hygiene, skin breakdown, and cosmesis. When these contractures become rigid, soft tissue procedures alone are unable to obtain or maintain the desired correction. In these patients’ wrist arthrodesis is an option—enabling the hand to be stabilized in a more functional position for hygiene, dressing, and general cosmesis, though are patients satisfied?

Methods:

All children who had undergone a wrist arthrodesis for the management of a severe wrist contracture at Shriners Hospital, Portland between January 2016 and January 2021 were identified (n=23). A chart review was undertaken to obtain data—demographic, operative, clinical, and radiographic. All patients were then contacted to participate in 2 patient-reported outcome questionnaires (74% response agreement), a numerical rating scale (NRS), based on the visual analog scale (VAS) and the disability analog scale (DAS). Results were assessed with the aid of descriptive statistics, means and percentages with the primary focus of determining overall patient satisfaction with the procedure.

Results:

Twenty-three patients were included in the review, and 74% took part in the prospective survey. Included were 10 patients with hemiplegia, 4 with triplegia, 7 with quadriplegia, 1 with a diagnosis of Rhett syndrome, and 1 with a history of traumatic brain injury. All patients achieved radiologic union by a mean of 8 weeks, and 87% obtained a neutral postoperative wrist alignment. The NRS showed 88% of patients were highly satisfied with their results; specifically, 82% had an improved appearance, 53% improved function, 71% improved daily cares, and 65% improved hygiene. The postoperative DAS score averaged 4.7 of 12 indicating mild disability. When looking at how a patient’s diagnostic subtype affected outcome results, patients with triplegia reported less improvement and greater disability on the NRS and DAS, averaging 9.5 (severe disability on the DAS). The GMFCS classification had less correlation with outcomes.

Conclusion:

Wrist arthrodesis is a good option for the management of pediatric spastic wrist contractures, with limited complications and an overall high patient/carer satisfaction rate.

Level of evidence:

Level IV—case series.
Opioid receptor antagonists reduce motivated wheel-running behavior in mice
Authors: Kitanaka Nobue , Arai Kanayo , Takehara Kaoko , Hall F. Scott , Tomita Kazuo , Igarashi Kento , Sato Tomoaki , Uhl George R. , Kitanaka Junichi
Published: March 2024

We hypothesized that opioid receptor antagonists would inhibit motivated behavior produced by a natural reward. To evaluate motivated responses to a natural reward, mice were given access to running wheels for 71.5 h in a multi-configuration testing apparatus. In addition to a running wheel activity, locomotor activity (outside of the wheel), food and water intake, and access to a food container were measured in the apparatus. Mice were also tested separately for novel-object exploration to investigate whether naloxone affects behavior unrelated to natural reward. In untreated mice wheel running increased from day 1 to day 3. The selective µ-opioid receptor antagonist β-funaltrexamine (β-FNA) (5 mg/kg) slightly decreased wheel running, but did not affect the increase in wheel running from day 1 to day 3. The non-selective opioid receptor antagonist naloxone produced a greater reduction in wheel running than β-FNA and eliminated the increase in wheel running that occurred over time in the other groups. Analysis of food access, locomotor behavior, and behavior in the novel-object test suggested that the reduction in wheel running was selective for this highly reinforcing behavior. These results indicate that opioid receptor antagonism reduces responses to the natural rewarding effects of wheel running and that these effects involve multiple opioid receptors since the non-selective opioid receptor antagonist had greater effects than the selective µ-opioid receptor antagonist. It is possible that at the doses employed, other receptor systems than opioid receptors might be involved, at least in part, in the effect of naloxone and β-FNA.
Clinical outcomes and prognostic factors after HCV clearance with DAA in HIV/HCV-coinfected patients with advanced fibrosis/cirrhosis
Authors: Berenguer Juan , Aldámiz-Echevarría Teresa , Hontañón Víctor , Fanciulli Chiara , Quereda Carmen , Busca Carmen , Domínguez Lourdes , Hernández Cristina , Vergas Jorge , Gaspar Gabriel , García-Fraile Lucio J. , Díez Cristina , De Miguel Marta , Bellón José M. , Bañares Rafael , González-García Juan
Published: March 2024

Background and Aims:

We assessed long-term clinical outcomes and prognostic factors for liver disease progression after sustained viral response with direct-acting antivirals in patients coinfected with HIV/HCV with advanced fibrosis or cirrhosis.

Approach and Results:

A total of 1300 patients who achieved sustained viral response with direct-acting antivirals from 2014 to 2017 in Spain were included: 1145 with compensated advanced chronic liver disease (384 advanced fibrosis and 761 compensated cirrhosis) and 155 with decompensated cirrhosis. The median follow-up was 40.9 months. Overall, 85 deaths occurred, 61 due to non-liver non-AIDS–related causes that were the leading cause of death across all stages of liver disease. The incidence (95% CI) of decompensation per 100 person-years (py) was 0 in patients with advanced fibrosis, 1.01 (0.68–1.51) in patients with compensated cirrhosis, and 8.35 (6.05–11.53) in patients with decompensated cirrhosis. The incidence (95% CI) of HCC per 100 py was 0.34 (0.13–0.91) in patients with advanced fibrosis, 0.73 (0.45–1.18) in patients with compensated cirrhosis, and 1.92 (1.00–3.70) per 100 py in patients with decompensated cirrhosis. Prognostic factors for decompensation in patients with compensated advanced chronic liver disease included serum albumin, liver stiffness measurement (LSM), and fibrosis 4. In this population, LSM and LSM-based posttreatment risk stratification models showed their predictive ability for decompensation and HCC.

Conclusions:

Non-liver non-AIDS–related events were the leading causes of morbidity and mortality after direct-acting antiviral cure among coinfected patients with advanced fibrosis/cirrhosis. Among those with compensated advanced chronic liver disease, baseline LSM and posttreatment LSM-based models helped to assess decompensation and HCC risk.
Assessment and Treatment of Abnormal Involuntary Movements: A Clinically Focused Narrative Review
Authors: Petriceks Aldis , Vyas Chirag M. , Paudel Shreedhar , Donovan Abigail L. , Van Alphen Manjola U. , Stern Theodore A.
Published: March 2024

Learning Objectives

After participating in this CME activity, the psychiatrist should be better able to:

• Categorize and describe different types of abnormal involuntary movements (AIMs).

• Identify assessment tools and treatment options for AIMs.

Abnormal involuntary movements (AIMs) comprise a diverse group of movement disorders characterized by uncontrolled and unintended movements (e.g., tremors, tics, dystonia). AIMs can occur at any stage of life and pose significant challenges for clinicians. It is difficult to determine their underlying causes due to the complex neurobiological mechanisms involved. Therefore, it is crucial to quantify the severity and progression of AIMs using well-validated measurement scales, such as the Abnormal Involuntary Movement Scale (AIMS). By employing reliable assessment approaches, clinicians can objectively evaluate the motoric manifestations of AIMs and track them over time. Treatment of AIMs varies depending on their nature and etiology. While AIMs often respond to treatment, serious side effects can undermine treatment efficacy. In this clinically focused narrative review, we categorize different types of AIMs and discuss their neurobiological aspects. Further, we emphasize the importance of using well-validated measurement scales for accurate assessment and discuss available treatment modalities that target the specific AIMs manifestations. Additionally, we cover the need for comprehensive care to address the multifaceted nature of AIMs, accounting for their physical manifestations as well as their psychological, social, and functional toll on patients. By embracing a multidisciplinary approach, health care professionals can provide patient-centered care that promotes overall well-being and enhances the lives of patients coping with AIMs. Regular follow-up assessments are necessary to monitor treatment response, adjust medications when needed, and provide ongoing support for individuals affected by AIMs.
Readiness and Personality Disorders: Considering Patients’ Readiness for Change and Our System’s Readiness for Patients
Authors: Hawkins Connor , Kealy David
Published: March 2024

The culture around personality disorder treatment has changed drastically in the past generation. While once perceived as effectively untreatable, there are now numerous evidence-based treatment approaches for personality disorders (especially borderline personality disorder). The questions, however, of who should be matched to which treatment approach, and when, remain largely unanswered. In other areas of psychiatry, particularly substance use disorders and eating disorders, assessing patient treatment readiness is viewed as indispensable for treatment planning. Despite this, relatively little research has been done with respect to readiness and personality disorder treatment. In this article, we propose multiple explanations for why this may be the case, relating to both the unique features of personality disorders and the current cultural landscape around their treatment. While patients with personality disorders often face cruel stigmatization, and much more work needs to be done to expand access to care (i.e., our system’s readiness for patients), even gold-standard treatment options are unlikely to work if a patient is not ready for treatment. Further study of readiness in the context of personality disorders could help more effectively match patients to the right treatment, at the right time. Such research could also aid development of strategies to enhance patient readiness.
Comparison of Bordetella pertussis Antibody Levels in Pregnant Women and Umbilical Cord Blood: A Multicenter Study
Authors: Iseri Nepesov Merve , Kilic Halime , Yildirim Sukran , Gulec Sevgi , Kara Yalcin , Kizil Mahmut Can , Karbuz Adem , Terek Demet , Sutcu Murat , Tufan Ergun , Dinleyici Meltem , Kurugol Zafer , Kilic Omer , Dinleyici Ener Cagri
Published: March 2024

Background:

In countries where pertussis vaccination is not administered during pregnancy, the determination of pertussis antibody levels in pregnant women is very important in terms of knowing the current seroepidemiology and potential strategies for immunizations.

Methods:

We included 396 pregnant women who were admitted to 4 different obstetrics and gynecology clinics. Anti-Bordetella pertussis toxin (PT) IgG and anti-Bordetella pertussis filamentous hemagglutinin IgG levels in maternal and cord blood pairs were determined by the ELISA method.

Results:

Venous blood serum anti-PT level was below 5 IU/mL in 58.8%, 5–40 IU/mL in 34.8%, 40–100 IU/mL in 5.1% and >100 IU/mL in 1.3% of pregnant women. Cord blood serum anti-PT level was below 5 IU/mL in 47.7%, 5–40 IU/mL in 44.5%, 40–100 IU/mL in 6.8% and >100 IU/mL in 1% of pregnant women. In our study, the anti-PT level was found below 40 IU/mL in 93.6% of pregnant women and 92.2% of cord blood. Our study found the anti-filamentous hemagglutinin level below 40 IU/mL in 81% of pregnant women and 66.2% of cord blood.

Conclusions:

Although it is known that pertussis causes serious morbidity and mortality in young infants all over the world and that the most effective and reliable way to prevent it is vaccination of pregnant women, it is a remarkable contradiction that pertussis vaccination rates and therefore seropositivity rates in pregnant women are very low.
Pediatric Community-Acquired Brain Abscesses: A Single-center Retrospective Study
Authors: Lu Kevin Hai-Ning , Bruns Nora , Pentek Christina , Della Marina Adela , Gangfuß Andrea , Kölbel Heike , Dogan Burcin , Dziobaka Jan , Ahmadipour Yahya , Damman Philipp , Felderhoff-Müser Ursula , Dohna-Schwake Christian , Goretzki Sarah Christina
Published: March 2024

The European Society for Clinical Microbiology and Infectious Diseases recommends 3rd generation cephalosporins and metronidazole for empirical treatment of community-acquired brain abscesses. In 53 retrospectively analyzed pediatric patients with community-acquired brain abscesses at a German University Hospital Staphylococcus aureus was identified as a relevant pathogen (21%). Therefore, it may be reasonable to cover S. aureus when selecting empirical therapy.
Immediate vs. multistage revascularization of non-infarct coronary artery(-ies) in patients with hemodynamically stable multivessel disease acute myocardial infarction: a systematic review and meta-analysis
Authors: Oli Prakash Raj , Shrestha Dhan Bahadur , Dawadi Sagun , Shtembari Jurgen , Regmi Laxmi , Pant Kailash , Shrestha Bishesh , Mattumpuram Jishanth , Katz Daniel H.
Published: March 2024

Background

Untreated multivessel disease (MVD) in acute myocardial infarction (AMI) has been linked to a higher risk of recurrent ischemia and death within one year . Current guidelines recommend percutaneous coronary intervention (PCI) for significant non-infarct artery (-ies) (non-IRA) stenosis in hemodynamically stable AMI patients with MVD, either during or after successful primary PCI, within 45-days. However, deciding the timing of revascularization for non-IRA in cases of MVD is uncertain.

Methods

This meta-analysis was performed based on PRISMA guidelines after registering in PROSPERO (CRD42023472652). Databases were searched for relevant articles published before 10 November 2023. Pertinent data from the included studies were extracted and analyzed using RevMan v5.4.

Results

Out of 640 studies evaluated, there were 13 RCTs with 5144 patients with AMI with MVD. The immediate non-IRA PCI is associated with a significantly lower occurrence of unplanned ischemia-driven PCI (OR 0.60; confidence interval [CI] 0.44–0.83) and target-vessel revascularization (OR 0.72; CI 0.53–0.97) . Although there is a favorable trend for major adverse cardiovascular and cerebrovascular events (MACCE), nonfatal AMI, cerebrovascular events, and major bleeding in the immediate non-culprit artery (-ies) PCI, those were statistically non-significant. Similarly, all-cause mortality, cardiovascular mortality, stent thrombosis, and acute renal insufficiency did not show significant differences between two groups.

Conclusion

Among hemodynamically stable patients with multivessel AMI, the immediate PCI strategy was superior to the multistage PCI strategy for the unplanned ischemia-driven PCI and target-vessel revascularization while odds are favorable in terms of MACCE, nonfatal AMI, cerebrovascular events, and major bleeding at longest follow-up.
Does Radioactive Iodine Treatment Damage the Lacrimal System?
Authors: Gürez Ceren , Ergül Nurhan
Published: March 2024

Purpose

In this prospective study, we aimed to make a quantitative assessment of the lacrimal glands before and after radioactive iodine (RAI) treatment in patients with hyperthyroidism and thyroid cancer.

Methods

The study included 80 eyes of 40 patients. There were 25 patients in group 1 (hyperthyroid group) and 15 patients in group 2 (thyroid cancer group). Group 1 has received low dose (131I) and group 2 high dose (131I). Before, and at the first and sixth month after RAI treatment, all patients underwent ophthalmological examinations, Schirmer tests, TBUT tests, tear osmolarity (TO), and ocular surface examinations.

Results

The age and sex characteristics of both groups were similar. Although no significant change was observed in tear film tests before and after treatment in group 1, a significant decrease in Schirmer and TBUT values and a significant increase in TO were observed in group 2 in the first month after treatment. These values returned to normal in the sixth month. Although no Schirmer test was observed lower than 10 mm in any patient before RAI treatment, the Schirmer test was measured 5 to 10 mm in 4 (10%) patients in group 2 in the first month after treatment. Again, in these patients, TBUT was below 10 seconds and TO was greater than 308 mOsm/L.

Conclusions

In this study, although no change was observed in tear function tests in patients receiving low doses of RAI, a decrease in tear secretion and an increase in TO were detected in patients receiving high doses in the early period.
Sacrificing Internal Carotid Artery-External Carotid Artery-Radial Artery-Middle Cerebral Artery Bypass for the Treatment of Complex Intracranial Artery Cavernous Sinus Aneurysms
Authors: Chu Fudi , Song MaoYuan , Zhang Zheng , Pang Chunxiao , Wang JinPeng
Published: March 2024

The treatment of complex intracranial aneurysms has always been a great challenge in neurosurgery. Craniotomy has a high risk of clipping, there is a risk of rupture at any time, endovascular embolization is relatively low risk, but expensive and easy to relapse, the best treatment needs to be further discussed. Cavernous sinus aneurysms with pituitary adenomas are rare. This case reports a case of complex intracranial aneurysms. Chief complaints are: (1) blepharoptosis with blurred vision for 1 year, (2) headache for 3 days, and (3) digital subtraction angiography showed right internal carotid artery cavernous sinus aneurysm. Combined with the patient’s condition and family condition, the external carotid artery-radial artery-middle cerebral artery bypass was selected. After surgical treatment, the symptoms of the patients were improved, the postoperative recovery was good, and the condition was stable. After follow-up, the patient’s brain computed tomography showed intra-aneurysm thrombosis.
Foreign Glass Bodies in Pleura and Pancreas: Systematic Review for Entry Hypotheses and Treatment Options in an Unresolved Case
Authors: Ehrsam Jonas P. , Meier Adamenko Olga , Schlumpf Rolf B. , Schöb Othmar M.
Published: March 2024

Background:

Foreign bodies within the pleura and pancreas are infrequent, and the approaches to their treatment still a subject of debate. There is limited knowledge particularly regarding glass foreign bodies.

Methods:

We present a case involving large glass splinters in the pleura and pancreas, with an unknown entry point. In addition, a systematic review was conducted to explore entry hypotheses and management options.

Results:

In addition to our case, our review uncovered eight incidents of intrapleural glass, and another eight cases of glass in other intrathoracic areas. The fragments entered the body through impalement (81%), migrated through the diaphragm after impalement (6%), or caused transesophageal perforation (19%) following ingestion. Eight instances of glass inside the abdominal cavity were documented, with seven resulting from impalement injuries and one from transintestinal migration. There were no recorded instances of glass being discovered within the pancreas. Among the 41 nonglass intrapancreatic foreign bodies found, sewing needles (34%) and fish bones (46%) were the most common; following ingestion, they had migrated through either a transgastric or transduodenal perforation. In all these cases, how the foreign bodies were introduced was often poorly recalled by the patient. Many nonglass foreign bodies tend to become encapsulated by fibrous tissue, rendering them inert, though this is less common with glass. Glass has been reported to migrate through various tissues and cavities, sometimes with a significant delay spanning even decades. There are cases of intrapleural migration of glass causing hemothorax, pneumothorax, and heart and major blood vessels injury. For intrapleural glass fragment management, thoracoscopy proved to be effective in 5 reported cases, in addition to our patient. Most intrapancreatic nonglass foreign bodies tend to trigger pancreatitis and abscess formation, necessitating management ranging from laparoscopic procedures to subtotal pancreatectomy. There have been only four documented cases of intrapancreatic needles that remained asymptomatic with conservative management. There is no direct guidance from the existing literature regarding management of intrapancreatic glass foreign bodies. Consequently, our patient is under observation with regular follow-ups and has remained asymptomatic for the past 2 years.

Conclusions:

Glass foreign bodies in the pleura are rare, and our report of an intrapancreatic glass fragment is the first of its kind. Impalement is the most likely method of introduction. As glass has significant migration and an ensuing complication potential, preventive removal of intrapleural loose glass should be considered. However, intrapancreatic glass fragment management remains uncertain.
Comparative analysis of virulence gene profiles of Escherichia coli from clinical and non-clinical sources in Rivers State, Nigeria

Authors: Abeni Barira Azeez , Frank-Peterside Nnenna , Otokunefor Kome
Published: March 2024

Traditionally, the presence of virulence features have been thought to be a key factor in differentiating pathogenic from commensal strains. An understanding of virulence potential of Escherichia coli isolates from various sources is essential to help shed light on potential contamination/transmission rates between the various sources. This study was therefore aimed at exploring the occurrence of specific virulence genes and gene profiles associated with Escherichia coli from clinical and non-clinical sources in Rivers State, Nigeria.
Two hundred samples from clinical (urine and feces) and non-clinical (soil and poultry droppings) sources (50 each) were analyzed using standard microbiological procedures. DNA was extracted from isolates presumptively identified as Escherichia coli using PrestoTM Mini gDNA Bacteria-Kit Quick protocol following the manufacturer’s instructions. Isolate identities were confirmed using E. coli specific 16S rRNA primers and confirmed isolates screened for the presence of six virulence genes (Afimbriae binding adhesin (afa), type 1 fimbriae (fimH), P-fimbrial Usher Protein (papC)), iron acquisition systems: aerobactin (aer), Cytotoxic necrotizing factor I (cnf1) and alpha hemolysin (hly).
Results showed that all isolates haboured at least one of the tested virulence genes, with fimH (97%) as the most prevalent virulence gene and papC the least commonly occurring (35%). A higher occurrence of virulence genes was noted in non-clinical isolates though hly and cnf were not detected at all in any of the isolates studied (0%). Ten different profiles were observed with the afaCc-aer-fimH profile the most commonly occurring virulence gene profile in general (33.3%). For non-clinical isolates however, the aer-afaCc-fimH-papC was the most commonly occurring profile (42.9%).
This study shows that the test Escherichia coli from clinical and non-clinical sources do not carry distinct virulence gene profiles. Studies on a larger subset of isolates would however be necessary to determine if indeed the virulence genes tested for in this study really cannot be used to tell whether an isolate is from a clinical source or not in the South-South of Nigeria.
Keetia nodulosasp. nov. (Rubiaceae - Vanguerieae) of West - Central Africa: bacterial leaf nodulation discovered in a fourth genus and tribe of Rubiaceae
Authors: Cheek Martin , Onana Jean Michel
Published: March 2024

Keetia nodulosaCheek, a cloud forest climber nearly endemic to Cameroon, with a single record from Nigeria, is described and illustrated. It is remarkable as the first known species to be recorded with bacterial leaf nodules (BLN) in the genusKeetia,and also, in the tribe Vanguerieae. Other genera in Rubiaceae with BLN arePsychotria(Psychotrieae),Sericanthe(Coffeaeae) andPavetta(Pavetteae). The BLN inKeetia(Vanguerieae) are illustrated for the first time here.

The characteristics and significance of bacterial leaf nodulation inKeetia nodulosaare discussed in the context of rapidly growing knowledge on the subject in flowering plants.Keetia nodulosais provisionally assessed using the 2012 IUCN standard as Endangered (EN B2ab(iii). The importance of its conservation, and options for achieving this are discussed in the context of recent extinctions of other plant species in Cameroon.

This discovery of a new cloud forest species is discussed in relation to other cloud forest plant species described in the last twenty years which are also distributed over the highlands of the western half of Cameroon.
Hyaluronidase impacts exposures of long-acting injectable paliperidone palmitate in rodent models
Authors: Pertinez Henry , Kaushik Amit , Curley Paul , Arshad Usman , El-Khateeb Eman , Li Si-Yang , Tasneen Rokeya , Sharp Joanne , Kijak Edyta , Herriott Joanne , Neary Megan , Noë Michaël , Flexner Charles , Nuermberger Eric , Owen Andrew , Ammerman Nicole C.
Published: March 2024

A significant challenge in the development of long-acting injectable drug formulations, especially for anti-infective agents, is delivering an efficacious dose within a tolerable injection volume. Co-administration of the extracellular matrix-degrading enzyme hyaluronidase can increase maximum tolerable injection volumes but is untested for this benefit with long-acting injectable formulations. One concern is that hyaluronidase could potentially alter the tissue response surrounding an injection depot, a response known to be important for drug release kinetics of long-acting injectable formulations. The objective of this pilot study was to evaluate the impact of co-administration of hyaluronidase on the drug release kinetics, pharmacokinetic profiles, and injection site histopathology of the long-acting injectable paliperidone palmitate for up to four weeks following intramuscular injection in mouse and rat models. In both species, co-administration of hyaluronidase increased paliperidone plasma exposures the first week after injection but did not negate the overall long-acting release nature of the formulation. Hyaluronidase-associated modification of the injection site depot was observed in mice but not in rats. These findings suggest that further investigation of hyaluronidase with long-acting injectable agents is warranted.
Good practice in the provision of care for people living with dementia in nursing homes: a systematic review
Authors: Behan Laura , O’Brien Michael P , Dunbar Paul , McGrane Niall , Keane Aileen , Grogan Carol , Keyes Laura M
Published: March 2024

Background

The number of people living with dementia across the world is rising, and there is a high and ever increasing proportion of people with dementia living in nursing homes. It is increasingly important that care provision in these services accounts for the specific needs of this cohort. Manifestations of dementia are modifiable with high quality dementia specific care, as such, we need to understand what good practice looks like specifically in these settings.

Aim

To synthesise empirical research to identify the characteristics of quality in the provision of care for people living with dementia in nursing homes.

Methods

Four electronic academic databases were searched: Business Complete, CINAHL, MEDLINE and APA PsychInfo. Qualitative, quantitative or mixed-methods studies published between the years of 2020-2023, that aimed to identify determinants of high quality care for people with dementia living in nursing homes, were included. Themes relating to good practices were identified and narratively summarised. Vignettes illustrating good practice were constructed from the perspective of a provider, a staff member, a resident and a family member.

Results

After screening of 3,356 records, 30 articles were included. This included 16 qualitative descriptive studies, 11 cross-sectional studies, 2 mixed methods studies, and 1 cohort study. Sixteen themes were identified: determinants of care quality, outcomes, person-centred care, cultural impact, care planning, meaningful engagement, eating and meals, the role of family members, restrictive practices, psychotropic medications, activities, materials, health care, end of life care, staffing and staff training.

Conclusions

The literature identifies what constitutes high quality care for residents with dementia in nursing homes. These findings will guide those delivering care in nursing homes in their daily work and in the implementation of quality improvement processes. It will also direct regulators, policymakers and researchers when conducting future work in this important area.
Detection of an imported case of severe Crimean-Congo hemorrhagic fever virus in a patient with comorbidities, Dakar, Senegal 2023
Authors: Sagne Samba Niang , Sene Ousseynou , Dieng Idrissa , Diallo Mamadou Korka , Ndoye Amadou Moustapha , Sall Yoro , Diop Boly , Faye Oumar , Sow Abdourahmane , Diallo Boubacar , Loucoubar Cheikh , Fall Gamou , Barry Mamadou Aliou
Published: March 2024

In July 2023, a diabetic from Mauritania was diagnosed with a severe case of Crimean-Congo hemorrhagic fever at a Dakar region hospital, Senegal. The phylogenetic analysis revealed the new strain as a CCHFV reassortant between Genotype I and III, closely linked to strains from Spain, Mauritania, Senegal and South Africa. Genetic variability of CCHF in West Africa underscores the urgent need for enhanced surveillance in West Africa.
Circulating CD4+ T cells in people with HIV and history of pulmonary tuberculosis have more intact HIV DNA
Authors: Juste Marc Antoine Jean , Joseph Yvetot , Lespinasse Dominique , Apollon Alexandra , Jamshidi Parmida , Lee Myung Hee , Ward Maureen , Brill Esther , Duffus Yanique , Chukwukere Uche , Danesh Ali , Alberto Winiffer Conce , Fitzgerald Daniel W. , Pape Jean W. , Jones R. Brad , Dupnik Kathryn
Published: March 2024

Background

The primary barrier to curing HIV infection is the pool of intact HIV proviruses integrated into host cell DNA throughout the bodies of people living with HIV (PLHIV), called the HIV reservoir. Reservoir size is impacted by the duration of HIV infection, delay in starting antiretroviral therapy (ART), and breakthrough viremia during ART. The leading infectious cause of death worldwide for PLHIV is TB, but we don’t know how TB impacts the HIV reservoir.

Methods

We designed a case-control study to compare HIV provirus-containing CD4 in PLHIV with vs. without a history of active TB disease. Study participants in the pilot and confirmatory cohort were enrolled at GHESKIO Centers in Port au Prince, Haiti. Intact and non-intact proviral DNA were quantified using droplet digital PCR of PBMC-derived CD4 cells. For a subset, Th1 and Th2 cytokines were assayed in plasma. Kruskal-Wallis tests were used to compare medians with tobit regression for censoring.

Results

In the pilot cohort, we found that PLHIV with history of active pulmonary TB (n=20) had higher intact provirus than PLHIV without history of active TB (n=47) (794 vs 117 copies per million CD4, respectively; p<0.0001). In the confirmatory cohort, the quantity of intact provirus was higher in the TB group (n=13) compared with the non-TB group (n=18) (median 102 vs. 0 intact provirus per million CD4, respectively p=0.03). Additionally, we found that the frequencies of CD4+ T cells with any detectable proviral fragment was directly proportional to the levels of IL1B (p= 0.0025) and IL2 (p=0.0002).

Conclusions

This is the first assessment of HIV provirus using IPDA in a clinical cohort from a resource limited setting, and the finding of larger reservoir in PLHIV with history of TB has significant implications for our understanding of TB-HIV coinfection and HIV cure efforts in TB-endemic settings.
A meta-analysis approach to gene regulatory network inference identifies key regulators of cardiovascular diseases
Authors: Pepe G. , Appierdo R. , Ausiello G. , Helmer-Citterich M. , Gherardini PF.
Published: March 2024

Cardiovascular diseases (CVDs) represent a major concern for global health whose mechanistic understanding is complicated by a complex interplay between genetic predisposition and environmental factors.

Specifically, heart failure (HF), encompassing dilated cardiomyopathy (DC), ischemic cardiomyopathy (ICM), and hypertrophic cardiomyopathy (HCM), is a topic of substantial interest in basic and clinical research. Here we used a Partial Correlation Coefficient-based algorithm (PCC) within the context of a meta-analysis framework, to construct a Gene Regulatory Network (GRN) that identifies key regulators whose activity is perturbed in Heart Failure. By integrating data from multiple independent studies, our approach unveiled crucial regulatory associations between transcription factors (TFs) and structural genes, emphasizing their pivotal roles in regulating metabolic pathways, such as fatty acid metabolism, oxidative stress response, epithelial-to-mesenchymal transition, and coagulation. In addition to known associations, our analysis also identified novel regulators, including the identification of TFs FPM315 and MOVO-B, which are implicated in dilated cardiomyopathies, and TEAD1 and TEAD2 in both dilated and ischemic cardiomyopathies. Moreover, we uncovered alterations in adipogenesis and oxidative phosphorylation pathways in hypertrophic cardiomyopathy, and discovered a role for IL2 STAT5 signaling in heart failure.

Our findings underscore the importance of TFs activity in the initiation and progression of cardiac disease, highlighting their potential as pharmacological targets.
Mitochondrial dynamics regulate cell size in the developing cochlea
Authors: O’Sullivan James D. B. , Terry Stephen , Scott Claire A. , Bullen Anwen , Jagger Daniel J. , Mann Zoë F.
Published: March 2024

In multicellular tissues, cell size and shape are intricately linked with physiological function. In the vertebrate auditory organ, the neurosensory epithelium develops as a mosaic of sensory hair cells (HCs), and their glial-like supporting cells (SCs), which have distinct morphologies at different frequency positions along its tonotopic long axis. In the chick cochlea, the basilar papilla (BP), proximal (high-frequency) HCs are larger than their distal (low-frequency) counterparts, a morphological feature essential for frequency tuning. Mitochondrial dynamics, which constitute the equilibrium between fusion and fission, regulate differentiation and functional refinement across a variety of cell types. We investigate this a potential mechanism for cell size regulation in developing HCs. Using live imaging in intact BP explants, we identify distinct remodelling of mitochondrial networks in proximal compared to distal HCs. Manipulating mitochondrial dynamics in developing HCs alters their normal morphology along the proximal-distal (tonotopic) axis. Inhibition of the mitochondrial fusion machinery decreased proximal HC size, whilst promotion of fusion increased the distal HC size. We identify mitochondrial dynamics as a key regulator of HC size and morphology in developing inner ear epithelia.

Summary Statement

Mitochondrial remodelling drives developmental changes in cell size in the auditory sensory epithelium. Our data reveal a fundamental mechanism regulating cell size and frequency-place coding in the developing cochlea.
Astrocytes in the mouse suprachiasmatic nuclei respond directly to glucocorticoids feedback
Authors: Händler Kristian , Sreenivasan Varun K.A. , Pilorz Violetta , Bringas Jon Olano , Castañondo Laura Escobar , Bengoa-Vergniory Nora , Oster Henrik , Spielmann Malte , Astiz Mariana
Published: March 2024

The circadian timing system anticipates daily recurring changes in the environment to synchronize physiology. In mammals, the master pacemaker is the hypothalamic suprachiasmatic nuclei (SCN), which synchronizes “wake” functions by inducing the circadian release of Glucocorticoids (GCs) from the adrenal gland. GCs peak right before the active phase and set the time of peripheral clocks, however, it is still unclear whether the SCN respond to GCs feedback. While GCs influence directly the SCN during the perinatal period, the adult circuit is considered to be resistant to them, suggesting a reduction of GCs-sensitivity along development. To understand this mechanism, we followed the expression of GC receptor (GR) along mouse SCN development with single-cell resolution and show that GR is up-regulated in astrocytes as the circuit matures. We providein vivoandin vitroevidence that the adult SCN stays responsive to circulating GCs through the activation of GR in astrocytes. Astrocytes’ communication is necessary to induce the GC-dependent shift on the SCN clock. Our data provides insight into the development of the SCN and highlight a new role of astrocytes as time-keepers in the adult. This finding might shed light on how the circadian system adapts to jetlag or shift work.
Human Pluripotent Stem Cell Derived Organoids Reveal a Role for WNT Signaling in Dorsal-Ventral Patterning of the Hindgut
Authors: Qu Na , Daoud Abdelkader , Kechele Daniel O. , Múnera Jorge O.
Published: March 2024

The cloaca is a transient structure that forms in the terminal hindgut giving rise to the rectum dorsally and the urogenital sinus ventrally. Similarly, human hindgut cultures derived from human pluripotent stem cells generate human colonic organoids (HCOs) which also contain co-developing urothelial tissue. In this study, our goal was to identify pathways involved in cloacal patterning and apply this to human hindgut cultures. RNA-seq data comparing dorsal versus ventral cloaca in e10.5 mice revealed that WNT signaling was elevated in the ventral versus dorsal cloaca. Inhibition of WNT signaling in hindgut cultures biased their differentiation towards a colorectal fate. WNT activation biased differentiation towards a urothelial fate, giving rise to human urothelial organoids (HUOs). HUOs contained cell types present in human urothelial tissue. Based on our results, we propose a mechanism whereby WNT signaling patterns the ventral cloaca, prior to cloacal septation, to give rise to the urogenital sinus.
Targeting G9a translational mechanism of SARS-CoV-2 pathogenesis for multifaceted therapeutics of COVID-19 and its sequalae
Authors: Muneer Adil , Xie Ling , Xie Xuping , Zhang Feng , Wrobel John A. , Xiong Yan , Yu Xufen , Wang Charles , Gheorghe Ciprian , Wu Ping , Song Juan , Ming Guo-Li , Jin Jian , Song Hongjun , Shi Pei-Yong , Chen Xian
Published: March 2024

By largely unknown mechanism(s), SARS-CoV-2 hijacks the host translation apparatus to promote COVID-19 pathogenesis. We report that the histone methyltransferase G9a noncanonically regulates viral hijacking of the translation machinery to bring about COVID-19 symptoms of hyperinflammation, lymphopenia, and blood coagulation. Chemoproteomic analysis of COVID-19 patient peripheral mononuclear blood cells (PBMC) identified enhanced interactions between SARS-CoV-2-upregulated G9a and distinct translation regulators, particularly the N6-methyladenosine (m6A) RNA methylase METTL3. These interactions with translation regulators implicated G9a in translational regulation of COVID-19. Inhibition of G9a activity suppressed SARS-CoV-2 replication in human alveolar epithelial cells. Accordingly, multi-omics analysis of the same alveolar cells identified SARS-CoV-2-induced changes at the transcriptional, m6A-epitranscriptional, translational, and post-translational (phosphorylation or secretion) levels that were reversed by inhibitor treatment. As suggested by the aforesaid chemoproteomic analysis, these multi-omics-correlated changes revealed a G9a-regulated translational mechanism of COVID-19 pathogenesis in which G9a directs translation of viral and host proteins associated with SARS-CoV-2 replication and with dysregulation of host response. Comparison of proteomic analyses of G9a inhibitor-treated, SARS-CoV-2 infected cells, orex vivoculture of patient PBMCs, with COVID-19 patient data revealed that G9a inhibition reversed the patient proteomic landscape that correlated with COVID-19 pathology/symptoms. These data also indicated that the G9a-regulated, inhibitor-reversed, translational mechanism outperformed G9a-transcriptional suppression to ultimately determine COVID-19 pathogenesis and to define the inhibitor action, from which biomarkers of serve symptom vulnerability were mechanistically derived. This cell line-to-patient conservation of G9a-translated, COVID-19 proteome suggests that G9a inhibitors can be used to treat patients with COVID-19, particularly patients with long-lasting COVID-19 sequelae.
EVALUATION OF THE RELATIONSHIP BETWEEN ADVANCED MATERNAL AGE AND PREGNANCY OUTCOME: A SCOPING REVIEW
Authors: Eze Innocent Okafor , Ezechi Oliver Chukwujiekwu , Mohammed Ahmadu Shehu , Nwagha Uchenna Ifeanyi
Published: March 2024

Background

Childbirth at advanced maternal age (AMA) is increasing among women, and some studies have shown adverse outcomes. There is a need to map evidence on the subject to harness findings and identify research gaps for further studies. This scoping review aims to examine pertinent studies on AMA and its impact on pregnancy outcomes.

Methods

The Preferred Reporting Item for Systematic Review and Meta-Analysis (PRISMA) chart is employed for systematic data extraction. This review draws from Google Scholar, the Cochrane Library, Medline (via PubMed), and Embase (via OVID). For inclusion in this scoping review, articles must thoroughly examine and elucidate the effects, impacts, and relationships between advanced maternal age and pregnancy outcomes. A crucial prerequisite is that the articles undergo a peer-review process to ensure the reliability and credibility of the presented information. For this review, advanced maternal age is defined explicitly as women aged ≥35. However, studies focusing on women aged ≥40 are also considered, mainly if they are high quality. In terms of research methodology, both primary and secondary research will be eligible, encompassing systematic reviews and meta-analyses. This broad inclusion aims to capture a comprehensive overview of the existing literature on the subject. Furthermore, articles must be presented in the English language to facilitate a standardized and accessible analysis. This criterion ensures that language barriers do not impede the review’s ability to synthesize relevant information effectively.

Results

There are significant associations between advanced maternal age and poor pregnancy outcomes, even when adjusted for confounders.

Conclusions

The adverse pregnancy outcome due to maternal age alone may be due to placental dysfunction resulting from a relative deficiency in maternal cardiovascular adaptations to pregnancy, and this provides a window for further studies.