bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent Advances in Room‐Temperature Phosphorescence Metal–Organic Hybrids: Structures, Properties, and Applications
Authors: Li Xian , Wang Yuefei , Zhang Zaiyong , Cai Suzhi , An Zhongfu , Huang Wei
Published: October 2023

Metal–organic hybrid (MOH) materials with room‐temperature phosphorescence (RTP) have drawn attention in recent years due to their superior RTP properties of high phosphorescence efficiency and ultralong emission lifetime. Great achievement has been realized in developing MOH materials with high‐performance RTP, but a systematic study on MOH materials with RTP feature is lacking. This review highlights recent advances in metal–organic hybrid RTP materials. The molecular packing, the photophysical properties, and their applications of metal–organic hybrid RTP materials are discussed in detail. Metal–organic hybrid RTP materials can be divided into six parts: coordination polymers, metal–organic frameworks (MOFs), metal‐halide hybrids, organic ionic crystals, organic ionic polymers, and organic–inorganic hybrid perovskites. These RTP materials have been successfully applied in time‐resolved data encryption, fingerprint recognition, information logic gates, X‐ray imaging, and photomemory. This review not only provides the basic principles of designing RTP metal–organic hybrids, but also propounds the future research prospects of RTP metal–organic hybrids. This review offers many effective strategies for developing metal–organic hybrids with excellent RTP properties, thus satisfying practical applications.
Solvent‐Free Ultrafast Construction of Se‐Deficient Heterojunctions of Bimetallic Selenides toward Flexible Sodium‐Ion Full Batteries
Authors: Sun Zhong‐Hui , Qu Dong‐Yang , Han Dong‐Xue , Gu Zhen‐Yi , Guo Jin‐Zhi , Zhao Xin‐Xin , Ma Ying‐Ming , Zhao Bo‐Lin , Song Zhong‐Qian , Wu Xing‐Long , Niu Li
Published: October 2023

Flexible quasi‐solid‐state sodium ion batteries featuring their low‐cost, high safety and excellent mechanical strength have attracted widespread interest in the field of wearable electronic devices. However, the development of such batteries faces great challenges including the construction of interfacial compatible flexible electrode materials and addressing the high safety demands of electrolyte. Here selenium‐vacancies regulated bimetallic selenide heterojunctions anchored on waste cotton cloth‐derived flexible carbon cloth (FCC) with robust interfacial C‐Se‐Co/Fe chemical bonds as a flexible anode material (CCFSF) is proposed by ultrafast microwave pyrolysis method. Rich selenium vacancies and CoSe2/FeSe2−x heterostructures are synchronously formed that can significantly improve ionic and electronic diffusion kinetics. Additionally, a uniform carbon layer coating on the surface of Se‐deficient heterostructures endows it with outstanding structural stability. The flexible cathode (PB@FCC) is also fabricated by directly growing Prussian blue nanoparticles on the FCC. Furthermore, an advanced flexible quasi‐solid‐state Na‐ion pouch cell is assembled by coupling CCFSF anode, PB@FCC cathode with P(VDF‐HFP)‐based gel polymer electrolyte. The full cell not only demonstrates excellent energy storage performance but also robust mechanical flexibility and safety. The present work offers an effective avenue to achieve high safety flexible energy storage device, promoting the development of flexible wearable electronic devices.
Doped Carbon Dots Enable Highly Efficient Multiple‐Color Room Temperature Phosphorescence
Authors: Wang Xiaohan , Han Yuanyuan , Li Weihua , Li Junzhi , Ren Shihuan , Wang Maorong , Han Guangting , Yu Jianyong , Zhang Yuanming , Zhao Haiguang
Published: October 2023

Colloidal carbon dots (C‐dots) are considered as promising heavy‐metal‐free materials to achieve room‐temperature phosphorescence (RTP) properties for promising applications, such as photoelectronic devices, information encryption, and bio‐imaging. However, most of the current obtained RTP C‐dots have a short lifetime with a relatively low quantum yield (QY). In this work, the C‐dots large‐scale synthesized via a vacuum heating approach have multiple RTP emissions (blue, green, and yellow), a long RTP lifetime of as high as 1.92 s, and a high QY of 34.4% by selecting different types of precursors, which is superior to most of reported RTP C‐dots. The multiple atoms doping and strong bonding between neighbored C‐dots promoted by vacuum heating contributes to the excellent RTP properties. As a proof‐of‐concept, the as‐obtained RTP C‐dots are used as optical ink for flexible security codes, exhibiting a bright shape with a lifetime of 1.37 s. This work offers an efficient approach for producing large‐scale high‐quality RTP C‐dots, which can be applied to anti‐counterfeiting and information encryption systems.
Copper‐Catalyzed Regio‐ and Enantioselective Hydroboration of Difluoroalkyl‐Substituted Internal Alkenes
Authors: Zhao Tao‐Qian , Xu Hui , Tian Yu‐Chen , Tang Xiaodong , Dang Yanfeng , Ge Shaozhong , Ma Jun‐An , Zhang Fa‐Guang
Published: October 2023

Catalytic asymmetric hydroboration of fluoroalkyl‐substituted alkenes is a straightforward approach to access chiral small molecules possessing both fluorine and boron atoms. However, enantioselective hydroboration of fluoroalkyl‐substituted alkenes without fluorine elimination has been a long‐standing challenge in this field. Herein, a copper‐catalyzed hydroboration of difluoroalkyl‐substituted internal alkenes with high levels of regio‐ and enantioselectivities is reported. The native carbonyl directing group, copper hydride system, and bisphosphine ligand play crucial roles in suppressing the undesired fluoride elimination. This atom‐economic protocol provides a practical synthetic platform to obtain a wide scope of enantioenriched secondary boronates bearing the difluoromethylene moieties under mild conditions. Synthetic applications including functionalization of biorelevant molecules, versatile functional group interconversions, and preparation of difluoroalkylated Terfenadine derivative are also demonstrated.
Spatiotemporally controlled emergence of nanoparticle microvortices under electric field
Authors: Pan Qi , Lin Xijian , Wei Shiyuan , Su Jinghong , Zhao Hansen , Duan Xiaojie , Hu Guoqing , He Yan
Published: October 2023

Controlled assembly of nanoparticles (NPs) has garnered much interest over the past two decades. Beyond established techniques, new methods utilizing local short‐range or large‐scale long‐range interactions remain to be explored to achieve diverse micro‐ and nanoscale structures. Here, we report the controlled emergence of vortex‐pair arrays within monodispersed gold nanorods by applying a direct current electric field across a pair of sawtooth electrodes. By employing in situ darkfield microscopy and particle collective analysis, we elucidate the mechanism behind the formation and stabilization of the NP vortices, attributing it to the combined effects of the electrode shape, high NP density, and high solution viscosity. We further explore the controllability of the vortex‐pair arrays and obtain multiple complex vortice patterns. Our findings will facilitate the investigation of efficient and controlled dynamic assembly of NPs under external fields and help manufacture next‐generation optoelectronic functional materials.
Maximizing utility of neuropsychological measures in sex‐specific predictive models of incident Alzheimer's disease in the Framingham Heart Study
Authors: Ferretti Maria Teresa , Ding Huitong , Au Rhoda , Liu Chunyu , Devine Sherral , Auerbach Sanford , Mez Jesse , Gurnani Ashita , Liu Yulin , Santuccione Antonella , Ang Ting Fang Alvin
Published: October 2023

INTRODUCTION

Sex differences in neuropsychological (NP) test performance might have important implications for the diagnosis of Alzheimer's disease (AD). This study investigates sex differences in neuropsychological performance among individuals without dementia at baseline.

METHODS

Neuropsychological assessment data, both standard test scores and process coded responses, from Framingham Heart Study participants were analyzed for sex differences using regression model and Cox proportional hazards model. Optimal NP profiles were identified by machine learning methods for men and women.

RESULTS

Sex differences were observed in both summary scores and composite process scores of NP tests in terms of adjusted means and their associations with AD incidence. The optimal NP profiles for men and women have 10 and 8 measures, respectively, and achieve 0.76 mean area under the curve for AD prediction.

DISCUSSION

These results suggest that NP tests can be leveraged for developing more sensitive, sex‐specific indices for the diagnosis of AD.
Synthesis of Closed‐Heterohelicenes Interconvertible between Their Monomeric and Dimeric Forms
Authors: Matsuo Yusuke , Maeda Chihiro , Tsutsui Yusuke , Tanaka Takayuki , Seki Shu
Published: October 2023

Oxidative fusion reaction of cyclic heteroaromatic pentads consisting of pyrrole and thiophene gave closed‐heterohelicene monomers and dimers depending on the oxidation conditions. Specifically, oxidation with [bis(trifluoroacetoxy)iodo]benzene (PIFA) gave closed‐[7]helicene dimers connected at the β‐position of one of the pyrrole units with remarkably elongated C−C bonds of about 1.60 Å. Although this bond was intact against thermal and physical activations, homolytic bond dissociation took place in DMSO upon irradiation with UV light to give the corresponding monomers. Thus, interconversion between the closed‐helicene monomer and dimer was achieved. The optically pure dimer was photo‐dissociated into the monomers associated with a turn‐on of circularly polarized luminescence (CPL).
Evaluation of an Evidence‐Based Care Bundle for Preventing Hospital‐Acquired Pressure Injuries in High‐Risk Surgical Patients
Authors: Aloweni Fazila Binte Abu Bakar , Lim Siew Hoon , Agus Nur Liyana Binte , Ang Shin Yuh , Goh Meh Meh , Yong Patricia , Fook‐Chong Stephanie , Tucker‐Kellogg Lisa , Soh Chai Rick
Published: October 2023

The aim of this study was to evaluate the effectiveness of an evidence‐based care bundle to prevent perioperative pressure injuries. In a single facility, using a preintervention and postintervention quasi‐experimental design, we compared the pressure injury incidence rate for two patient groups (ie, before and after care bundle implementation). The bundle included a variety of elements, such as educating patients, applying protection, controlling skin moisture, and using pressure‐relieving devices according to the patient's risk. Before the intervention, patients received standard care before procedures that did not address risk for pressure injury development. The study involved a total of 944 patients, and the incidence of pressure injury was lower in the postintervention group than in the preintervention group (1.6% versus 4.8%; P < .001). However, the odds ratio was nonsignificant and therefore the clinical relevance of the bundle is unclear. Additional research with a control group and multiple sites is needed.
Permeation Dynamics of Active Swimmers Through Anisotropic Porous Walls
Authors: von Rüling Florian , Bakhchova Liubov , Steinmann Ulrike , Eremin Alexey
Published: October 2023

Natural habitats of most living microorganisms are distinguished by a complex structure often formed by a porous medium such as soil. The dynamics and transport properties of motile microorganisms are strongly affected by crowded and locally anisotropic environments. Using Chlamydomonas reinhardtii as a model system, we explore the permeation of active colloids through a structured wall of obstacles by tracking microswimmers' trajectories and analyzing their statistical properties. Employing micro‐labyrinths formed by cylindrical or elongated pillars, we demonstrate that the anisotropy of the pillar's form and orientation strongly affects the microswimmers' dynamics on different time scales. Furthermore, we discuss the kinetics of the microswimmer exchange between two compartments separated by an array of pillars.
Dual‐task difficulties as a risk factor for unemployment in people with multiple sclerosis
Authors: Kahraman Turhan , Temiz Hasretgul , Abasiyanik Zuhal , Baba Cavid , Ozakbas Serkan
Published: October 2023

Background

No study has investigated the impact of dual‐tasking difficulties as a risk factor for unemployment in people with multiple sclerosis (pwMS). The aim was to examine the influence of dual‐task performance on employment status and work difficulties and to identify the predictors of employment status in pwMS.

Methods

Eighty‐four pwMS, including 42 employed and 42 unemployed, participated in the study. Dual‐task difficulties were assessed using the Dual‐task Impact on Daily‐living Activities‐Questionnaire (DIDA‐Q), while dual‐task performance was evaluated through the 30‐second Walk Test and Nine‐Hole Peg Test, incorporating a cognitive task. Walking and cognitive function were also measured.

Results

Employed pwMS had better scores in walking, cognitive function, single and dual‐task performance than unemployed pwMS (p < .05). Lower scores in walking (odds ratio [OR] = 1.81, p < .001) and upper extremity‐related (OR = 1.44, p = .019) dual‐task performance and higher scores in the cognitive subscale of the DIDA‐Q questionnaire (OR = 1.20, p = .037) were significantly associated with higher odds of being unemployed. Among employed pwMS, DIDA‐Q subscales showed moderate‐to‐strong correlations with MSWSDQ‐23 scores. The other variables showed weak‐to‐moderate correlations with subscale and total scores of MSWSDQ‐23.

Conclusion

Cognitive function, as opposed to motor function, has been found to be a significant predictor of unemployment in pwMS.
Prosthetic rehabilitation of an edentulous patient with microstomia using digital and conventional methods: A case report
Authors: Moslemian Naeime , Hasanzade Mahya
Published: October 2023

Key Clinical Message

This study describes prosthetic rehabilitation an edentulous patient with microstomia. Maxillary preliminary and definitive impression were made by intraoral scanning and custom 2‐piece impression tray respectively to fabricate conventional denture.
Insect ear‐feeding impacts Gibberella ear rot and deoxynivalenol accumulation in corn grain
Authors: Singh Maninder P. , DiFonzo Christina D. , Fusilier Katlin M. , Kaur Harkirat , Chilvers Martin I.
Published: October 2023

High deoxynivalenol (DON) levels in corn (Zea mays L.) is a grain quality issue for many growers in the US Great Lakes region. High DON levels can be attributed to the interaction of environment, pathogen (Fusarium spp. causing ear rot), and hybrid susceptibility. However, ear‐feeding insects can provide easy access for fungal infection and increase DON accumulation, hence the evaluation of insect protection strategies such as hybrid insecticidal proteins is crucial. Field trials were conducted at four locations in Michigan to study the impact of hybrids insect protection trait on ear injury, ear rot infection, and DON levels. Fungicide application (prothioconazole at silking stage) was conducted at two locations and included non‐treated control. Insect feeding incidence (IFI) and ear rot incidence (ERI) were correlated at three locations but were stronger at locations with environments not conducive to fungal growth soon after silking. Correlation between IFI and DON was observed only at locations with highest insect pressure. Hybrid with Vip3A protein reduced IFI by >70% at all locations but lowered DON concentration at one out of three tested locations compared to non‐Vip3A hybrids. Fungicide application reduced ear rot severity at one of two locations but did not impact ERI or DON levels. Overall, results showed that ear‐feeding by insects can lead to an increase in ear rot and DON levels, and use of hybrids with Vip3A protein can reduce DON levels especially under high insect pressure.
Visible Light Activates Coumarin‐Caged mRNA for Cytoplasmic Cap Methylation in Cells
Authors: Bollu Amarnath , Schepers Helena , Klöcker Nils , Erguven Mehmet , Lawrence‐Dörner Ann‐Marie , Rentmeister Andrea
Published: October 2023

Protein synthesis is important and regulated by various mechanisms in the cell. Translation initiation in eukaryotes starts at the 5′ cap and is the most complex of the three phases of mRNA translation. It requires methylation of the N7 position of the terminal guanosine (m7G). The canonical capping occurs in the nucleus, however, cytoplasmic recapping has been discovered. It functions in switching mRNAs between translating and non‐translating states, but the individual steps are difficult to dissect. We targeted cytoplasmic cap methylation as the ultimate step of cytoplasmic recapping. We present an N7G photocaged 5′ cap that can be activated for cytoplasmic methylation by visible light. We report chemical and chemo‐enzymatic synthesis of this 5′ cap with 7‐(diethylamino)‐4‐methyl‐coumarin (DEACM) at the N7G and validate that it is not bound by translation initiation factor 4E (eIF4E). We demonstrate incorporation into mRNA, the release of unmethylated cap analog and enzymatic remethylation to functional cap 0 after irradiation at 450 nm. In cells, irradiation triggers translation of mRNAs with the N7G photocaged 5′ cap via cytoplasmic cap methylation.
Artificial Intelligence: From Buzzword to Useful Tool in Clinical Pharmacology
Authors: Shahin Mohamed H. , Barth Aline , Podichetty Jagdeep T. , Liu Qi , Goyal Navin , Jin Jin Y. , Ouellet Daniele
Published: October 2023

The advent of artificial intelligence (AI) in clinical pharmacology and drug development is akin to the dawning of a new era. Previously dismissed as merely technological hype, these approaches have emerged as promising tools in different domains, including health care, demonstrating their potential to empower clinical pharmacology decision making, revolutionize the drug development landscape, and advance patient care. Although challenges remain, the remarkable progress already made signals that the leap from hype to reality is well underway, and AI promises to offer clinical pharmacology new tools and possibilities for optimizing patient care is gradually coming to fruition. This review dives into the burgeoning world of AI and machine learning (ML), showcasing different applications of AI in clinical pharmacology and the impact of successful AI/ML implementation on drug development and/or regulatory decisions. This review also highlights recommendations for areas of opportunity in clinical pharmacology, including data analysis (e.g., handling large data sets, screening to identify important covariates, and optimizing patient population) and efficiencies (e.g., automation, translation, literature curation, and training). Realizing the benefits of AI in drug development and understanding its value will lead to the successful integration of AI tools in our clinical pharmacology and pharmacometrics armamentarium.
Unlocking Some Si‐Centered Reactivity of a 4,4’‐Dichloro‐1,4‐di‐hydro‐1,4‐phosphasiline
Authors: Ramachandran Mridhul R. K. , Brehm Philipp C. , Sasamori Takahiro , Streubel Rainer
Published: October 2023

To establish some steric protection at the P center of a tricyclic 1,4‐dihydro‐1,4‐phosphasiline, the potassium salt of a tricyclic 1,4‐dihydro‐1,4‐phosphasilin‐1‐ide was treated with triphenylmethyl chloride. Subsequently, the two Si‐bound diethylamino groups, were converted to give the SiCl2 derivative using HCl. The Si‐functionality could be used in substitution reactions thus giving Si‐dimethyl and Si‐dimethoxy derivatives. Reduction of the SiCl2 derivative at low temperature gave transient tricyclic silylene which could not be detected by NMR spectroscopy but successfully trapped by 1,3‐butadiene to give a P‐containing spiro‐silolene derivative. DFT studies provide insight into reduction and the silylene formation.
Blame‐avoidance and fragmented crisis management during the COVID‐19 pandemic in Switzerland
Authors: Mavrot Céline , Sager Fritz
Published: October 2023

This article studies how the prolonged pandemic situation impacted crisis governance in the federalized governance system of Switzerland. It examines how in this acute crisis situation, the responsibility for decision‐making fluctuated among governance levels, placing subnational states in a situation of uncertainty that caused a fragmented crisis management, and therefore suboptimal policy learning processes. The study is based on the case of COVID‐19 governance in Switzerland, where, as in many other European countries, the management of the first pandemic wave was very centralized. However, the federal government avoided taking a strong lead during the subsequent waves. Consequently, pandemic management was marked by numerous fluctuations regarding who was in charge of the main COVID‐19 decisions between the federal and subnational governance levels. A media analysis (February 2020–March 2022) and an analysis of the gray literature show that crisis governance and policy learning processes were scattered across levels of governance, which impeded the accumulation of knowledge and know‐how. The article analyses how crises can give way to blame games between the levels of governance, thus hampering a coordinated crisis management and policy learning processes across the different stages of the pandemic.
Comment on “Concurrent carboplatin and paclitaxel definitive radiation therapy for locally advanced head and neck cancer”
Authors: Li Xueting , Liu Lei
Published: October 2023

see pages 230‐231
Machine learning‐based prediction of osteoporosis in postmenopausal women with clinical examined features: A quantitative clinical study
Authors: Ullah Kainat A. , Rehman Faisal , Anwar Muhammad , Faheem Muhammad , Riaz Naveed
Published: October 2023

Osteoporosis is a skeletal disease that is commonly seen in older people but often neglected due to its silent nature. To overcome the issue of osteoporosis in men and women, we proposed an advanced prediction model with the help of machine learning techniques which can help to identify the potential occurrence of this bone disease by its advanced screening tools. To achieve more reliable and accurate results, various machine‐learning techniques were applied to the presented data sets. Moreover, we also compared the performance of our results with other existing algorithms to solely focus on the advanced features of the proposed methodology. The two data sets, the clinical tests of patients in Taiwan and medical reports of postmenopausal women in Korea through Korean Health and Nutrition Examination Surveys (2010–2011) were considered in this study. To predict bone disorders, we utilized the data about females and developed a system using artificial neural networks, support vector machines, and K‐nearest neighbor. To compare the performance of the model Area under the Receiver Operating Characteristic Curve and other evaluation metrics were compared. The achieved results from all the algorithms and compared them with Osteoporosis Self‐Assessment Tool for Asians and the results were noticeably better and more reliable than existing systems due to the involvement of ML. Using machine learning techniques to predict these types of diseases is better because physicians and patients can take early action to prevent the consequences in advance.
Economic policy uncertainty and access to finance: An international evidence
Authors: Benlemlih Mohammed , Vural Yavaş Çiğdem , Assaf Cynthia
Published: October 2023

In this study, we provide the first attempt to relate economic policy uncertainty (EPU) to firms' access to finance. Using data from 26 countries and the news‐based index from Baker et al. (2016), we provide evidence that EPU significantly increases financial constraints and decreases firms' access to finance. Our main inference is robust to alternative measures of financial constraints, alternative samples, alternative model specifications, and several approaches that control for potential endogeneity. We further show that the EPU‐financial constraint relationship is driven by both the demand and supply sides of financing. Additional analyses suggest that the impact of EPU on firms' financial constraints is moderated by board characteristics (i.e., gender diversity, independence, and duality). They also highlight the moderating roles of government effectiveness, the rule of law and control of corruption. Collectively, our findings provide novel theoretical and practical contributions in relation to EPU and the firms' setting.
A Study of Danazol's Safety
Authors: Jick Susan S. , Myers Marian Wald
Published: October 2023

In a review of medical records of 530 recipients of danazol at Group Health Cooperative of Puget Sound, we identified 154 (29%) people who reported at least one adverse event that occurred within 45 days after receiving the drug. In no patient did the event require hospitalization, and there were no known long‐term sequelae.
The Effects of Age And Chemotherapy on Gentamicin Pharmacokinetics and Dosing in Pediatric Oncology Patients
Authors: Ho Katherine K. , Bryson Scott M. , Thiessen Jake J. , Greenberg Mark L. , Einarson Tom R. , Leson Cheryl L.
Published: October 2023

We attempted to determine the effects of prior antineoplastic chemotherapy and age on gentamicin pharmacokinetics in children (age 1–18 yrs) with cancer and in controls, and to establish a protocol for gentamicin dosing and monitoring to ensure rapid attainment of therapeutic serum concentrations in these patients. In a prospective controlled study, patients with fever who were receiving empiric gentamicin for confirmed or suspected infections were separated into three groups: 29 with cancer who were receiving a continuing chemotherapy protocol with nonnephrotoxic antineoplastic agents; 23 with cancer who were receiving a continuing chemotherapy protocol with nephrotoxic antineoplastic agents; and 25 control patients who did not have cancer. Three blood samples (one predose, two postdose concentrations), collected between the third and sixth gentamicin doses from each patient, were analyzed by the Emit assay. Pharmacokinetic parameters were calculated and gentamicin dosages recommended based on the Sawchuk‐Zaske method of serum level interpretation. When normalized by body weight, there was no significant difference in clearance, volume of distribution, and half‐life between the control group and either group of patients with cancer. However, when normalized by body surface area, patients receiving prior nephrotoxic chemotherapy appeared to have a lower mean clearance (98.2 ml/min/1.73 m2) than those exposed to nonnephrotoxic chemotherapy (117.4 ml/min/1.73 m2) and controls (113.3 ml/min/1.73 m2; ANCOVA p=0.033). When kinetic parameters were normalized by body weight, the effect of advancing age yielded a decrease in both clearance (p<0.001) and volume of distribution (p=0.02), and an increase in gentamicin half‐life (p<0.001). When normalized by body surface area, age had no significant effect on clearance (p=0.579). There was no significant difference in gentamicin daily dose requirements (mg/kg) between the chemotherapy groups, which may be due to the lack of significant effects of chemotherapy on gentamicin's volume of distribution and clearance normalized by body weight. The final maintenance doses (mg/kg/day mean ± SD) for patients with cancer were 10.8 ± 1.8 for those age 1–5 years, 8.9 ± 1.1 for those age 6–12 years, and 7.9 ± 1.9 for those age 13–18 years. However, when normalized by body surface area, the age‐dependent doses became remarkably similar for children in all three age groups (ANOVA p=0.932), approximately 250 mg/m2/day. We recommend that pediatric patients with cancer who require treatment for fever and neutropenia be given higher than standard gentamicin dosages to achieve therapeutic serum concentrations promptly. In particular, initial empiric doses of 10 mg/kg/day are appropriate for those age 1–5 years.
High‐Performance Capillary Electrophoresis in the Pharmaceutical Sciences
Authors: Brunner Lane J. , DiPiro Joseph T. , Feldman Stuart
Published: October 2023

High‐performance capillary electrophoresis (HPCE) is a new separation technique that is applied in the pharmaceutical sciences. Separations by HPCE occur in a narrow‐bore capillary under the influence of an applied electrical field. Components of the sample matrix are separated and migrate at different rates based on physicochemical properties, including ionic charge, charge to mass ratio, lipid solubility, and spatial orientation. Detection is achieved through an on‐line capillary detection window. The technique has several advantages, such as rapid analysis times, automation, and minute sample volume requirements. However, a significant disadvantage of HPCE is the high concentration limit of detection. Although HPCE will not displace traditional separation techniques, it will add another dimension to existing laboratories.
The Effect of Isoflurane versus Balanced Anesthesia on Rocuronium's Pharmacokinetics and Infusion Requirement
Authors: Larijani Ghassem E. , Gratz Irwin , Afshar Mary , McDonald Patricia A. , Fisher Dennis M.
Published: October 2023

Study Objective. To compare the effects of two anesthetic techniques, balanced and isoflurane anesthesia, on the response to an intubating dose and an infusion of rocuronium, and on rocuronium's pharmacokinetics.

Design. Randomized, open‐label study.

Setting. A university‐affiliated hospital.

Patients. Twenty‐two healthy adults undergoing elective surgery.

Interventions. The patients were anesthetized with a balanced technique (nitrous oxide, fentanyl, midazolam) or isoflurane (nitrous oxide, isoflurane 0.5‐1.0%). Rocuronium was administered initially as a 500‐μg/kg bolus, then by infusion to maintain approximately 86–94% depression of twitch tension. Plasma samples to determine rocuronium concentrations were obtained before, during, and after the infusion. Pharmacokinetics were determined using a population‐based approach.

Measurements and Main Results. Onset time and initial recovery after the bolus dose were similar for the two groups. Infusion requirements also were similar. Plasma clearance was greater during isoflurane than during balanced anesthesia (4.48 vs 3.49 ml/kg/min). Distribution clearances and volumes of distribution were similar for the two groups.

Conclusions. The similarity of response to an intubating dose and an infusion of rocuronium suggests that clinicians need not alter the dose or rate of rocuronium administration during isoflurane anesthesia with a of duration less than 1 hour. However, the greater clearance of rocuronium, in light of the similarity of infusion requirements, suggests that isoflurane potentiates rocuronium compared with balanced anesthesia.
Hemodynamic Effects of Intravenous Famotidine in Critically Ill Patients
Authors: Lipsy Robert J. , Freeman Collin D.
Published: October 2023

Study Objective: To study the hemodynamic effects of famotidine administered undiluted intravenously over 2 minutes.

Design: Nonblinded, nonrandomized.

Setting: Medical/surgical intensive care unit in a university‐affiliated, tertiary care, teaching hospital.

Patients: Eleven consecutive critically ill patients receiving famotidine for stress ulcer prophylaxis. Seven of these patients were also receiving vasopressors or inotropes.

Interventions: Famotidine 20 mg/2 ml was administered intravenously undiluted through a peripheral line over 2 minutes. All other medications, including vasopressors and inotropes, were held constant.

Measurements and Main Results: No clinically important (> 20 variations from baseline) or statistically significant (p<0.05) changes were seen in heart rate, mean pulmonary arterial pressure, cardiac output, systolic/diastolic blood pressure, systemic vascular resistance, or central venous pressure. Mean arterial pressure (MAP) was elevated at 8 minutes following famotidine (91.2 mm Hg [22.4 SD]) versus baseline (86.7 mm Hg [19.6 SD]). Pulmonary capillary wedge pressure (PCWP) was elevated at 8 minutes (17.2 mm Hg [6 SD]), 12 minutes (17.9 mm Hg [5.68 SD]), and 16 minutes (17.8 mm Hg [6.08 SD]), versus baseline (14.8 mm Hg [7.14 SD]). These changes in MAP and PCWP achieved statistical significance, but were not thought to be of clinical significance.

Conclusions: Famotidine given undiluted intravenously over 2 minutes produced no adverse hemodynamic effects in critically ill patients. Administration in this manner should be safe even in patients requiring supportive cardiovascular drug therapy.
The Effect of Prophylactic Nifedipine on Renal Function in Patients Administered Contrast Media
Authors: Khoury Ziad , Schlicht John R. , Como Jennifer , Karschner Janet Kimberly , Shapiro Alvin R , Mook William J. , Weber Robert J.
Published: October 2023

Study Objective. To determine if prophylaxis with nifedipine could decrease the frequency of contrast medium‐induced renal impairment.

Design. Prospective, randomized clinical trial.

Setting. A university‐affiliated hospital.

Patients. Patients undergoing scheduled radiologic examinations involving infusion of contrast media.

Interventions. Forty‐two patients were randomized to receive nifedipine 10 mg orally 1 hour before the imaging procedure, and 43 to receive no treatment.

Measurements and Main Results. Baseline serum creatinine levels were compared with maximum levels 24 and 48 hours after administration of contrast medium. No statistically significant difference was seen in either the mean change or mean percentage change in serum creatinine between the control and nifedipine groups. The mean changes in serum creatinine were +7.4 μmol/L in the control group and +2.7 μmol/L in the nifedipine group (p=0.33); the mean percentage changes were +10.2% and +4.8%, respectively (p=0.54).

Conclusion. Regardless of statistical analysis, it is unlikely that elevations in serum creatinine of this magnitude (< 0.1 mg/dl) are of clinical significance. We therefore conclude that prophylactic nifedipine is not clinically beneficial in preserving renal function in patients receiving contrast medium and that the agent should not be routinely administered for this purpose.
Rationale and Experience in Treating Suspected Hospital‐Based Mixed Infections
Authors: Billeter Marianne
Published: October 2023

Ochsner Foundation Hospital of the Ochsner Medical Institutions (OMI), a 532‐bed tertiary care facility in New Orleans, uses a formulary review process common to many institutions. Considered in the selection of antimicrobial therapy are efficacy, safety, and cost. At OMI, ticarcillin‐clavulanate plus gentamicin are the standard broad‐spectrum antimicrobial agents for initial treatment of suspected mixed infections. The pharmacy department provides an aminoglycoside‐monitoring program and convenient dosing guidelines. The regimen has resulted in good therapeutic outcomes and few adverse effects. Bacterial resistance has not been detected. Future plans include a large‐scale concurrent review of patient outcomes, resistance patterns, and rates of fungal overgrowth associated with these agents.
Comparative Evaluation of the Hemodynamic Effects of Oral Cimetidine, Ranitidine, and Famotidine as Determined by Echocardiography
Authors: Welage Lynda S. , Dunn‐Kucharski Valerie A. , Berardi Rosemary R. , Shea Michael J. , Dechert Ronald E. , Bleske Barry E.
Published: October 2023

Study Objective. To evaluate the influence of cimetidine, ranitidine, famotidine, and placebo on cardiac performance as determined by echocardiography.

Design. Randomized, four‐way crossover trial.

Setting. Echocardiography laboratory at a university hospital.

Participants. Twelve healthy volunteers.

Interventions. Volunteers received oral treatment with placebo, cimetidine 800 mg, ranitidine 300 mg, or famotidine 40 mg once/day for 7 days.

Measurements and Main Results. On the seventh day of each study phase, 2 hours after administration of the final dose, each subject underwent cardiac echocardiography and Doppler flow studies. No significant differences were detected in ejection fraction, peak flow velocity, or percentage fractional shortening among the treatment phases. A large degree of variability in ejection fraction was observed, with some subjects experiencing marked decreases.

Conclusion. The histamine‐2 (H2)‐receptor antagonists had no effect on the hemodynamic variables as determined by echocardiography. The variability in the hemodynamic response may in part explain the conflicting results reported in the literature. It also raises the question as to whether certain individuals are more sensitive to the potential cardiac effects of H2‐receptor antagonists.
Variable Disposition of Ciprofloxacin in Critically Ill Patients Undergoing Continuous Arteriovenous Hemodiafiltration
Authors: Fish Douglas N. , Bainbridge Jacquelyn L. , Peloquin Charles A.
Published: October 2023

Continuous arteriovenous hemodiafiltration (CAVHD) is being used increasingly in critically ill patients with acute renal failure (ARF). We prospectively evaluated extracorporeal and total systemic clearances (ClCAVHD and Cls) of ciprofloxacin during CAVHD in four patients with severe ARF to assess the adequacy of drug dosing. Ciprofloxacin serum and ultrafiltrate concentrations were measured by high‐performance liquid chromatography. The ClCAVHD accounted for approximately 5.9% (range 2.8–11.6%) of Cls of ciprofloxacin. However, large variability in serum concentrations was observed with the normally recommended dose of 400 mg/day, and doses of up to 800 mg/day were required to maintain concentrations suitable for treatment of serious infections. High daily doses of ciprofloxacin required in these patients are likely related to altered pharmacokinetics in serious illness as well as to the increased extracorporeal clearance during CAVHD. Clinical studies to define appropriate dosing recommendations for ciprofloxacin during CAVHD are necessary to guide clinicians in optimum drug use.
Flucytosine Dosing in an Obese Patient With Extrameningeal Cryptococcal Infection
Authors: Gillum J. Gregory , Johnson Mark , Lavoie Suzanne , Venitz Jurgen
Published: October 2023

A 31‐year‐old, obese woman with extrameningeal cryptococcal disease was admitted to the Medical College of Virginia for antifungal therapy. Various physiologic variables influence flucytosine pharmacokinetics, and there are no guidelines for dosing the agent in obese patients. This patient received a dosage based on her ideal body weight, and serum drug concentrations were monitored. She recovered without sequelae.
Economic Evaluations of Clinical Pharmacy Services—1988–1995
Authors:   Publications Committee of the American College of Clinical Pharmacy, Schumock Glen T. , Meek Patrick D. , Ploetz Pamela A. , Vermeulen Lee C.
Published: October 2023

The objectives of this effort were to summarize and critique original economic assessments of clinical pharmacy services published from 1988–1995, and to make recommendations for future work in this area. A literature search was conducted to identify articles that were then blinded and randomly assigned to reviewers to confirm inclusion, abstract information, and assess the quality of study design. The 104 articles fell into four main categories based on type of service described: disease state management (4%), general pharmacotherapeutic monitoring (36%), pharmacokinetic monitoring services (13%), and targeted drug programs (47%). Articles were categorized by type of evaluation; 35% were considered outcome analyses, 32% outcome descriptions, and 18% full economic analyses. A majority (89%) of the studies reviewed described positive financial benefits from the clinical services evaluated; however, many (68%) did not include the input costs of providing the clinical service as part of the evaluation. Studies that were well conducted were most likely to demonstrate positive results. Commonly, results were expressed as net savings or costs avoided for a given time period or per patient. Seven studies expressed results as a benefit:cost ratio (these ranged from 1.08:1 to 75.84:1, mean 16.70:1). Overall this body of literature contains a wealth of information pertinent to the value of the clinical practice of pharmacy. Future economic evaluations of clinical pharmacy services should incorporate sound study design and evaluate practice in alternative settings.
The Emergence of Peripheral Blood Progenitor Cells to Support Intensive Chemotherapy for Patients with Breast Cancer
Authors: Demetri George D.
Published: October 2023

Increasing evidence supports the hypothesis that “dose” is critical to the clinical outcomes of cytotoxic chemotherapy for patients with breast cancer. Clinical trials continue to investigate whether higher doses of chemotherapy lead to proportionate improvements in the outcomes of patients. Delivery of dose‐intensive chemotherapy has been facilitated by technological advancements in supportive care. Improved antiemetics have led to increased patient tolerance of the most acute symptoms of aggressive chemotherapeutic dosing. Chemotherapy‐induced myelosuppression may be minimized in a lineage‐specific manner by appropriate use of hematopoietic cytokines such as filgrastim (granulocyte colony‐stimulating factor), sargramostim (granulocyte‐macrophage colony‐stimulating factor), and/or epoetin alfa (erythropoietin). However, cumulative myelotoxicity occurs with dose‐intensive chemotherapy over multiple cycles despite adjunctive cytokine support. Additionally, no cytokine has yet been demonstrated to support platelet production to any clinically significant degree although several regulators of platelet production (such as thrombopoietin, IL‐6, and IL‐11) are in clinical trials. Many cytokines can induce the mobilization of hematopoietic progenitor and stem cells from the bone marrow into the circulating blood pool, where these cells may be harvested. Clinical use of these cytokine‐mobilized peripheral blood progenitor cells (also known as PBPCs or, commonly, as blood stem cells) has documented the effectiveness of these cells to reconstitute multilineage blood production following very high‐dose chemotherapy. The ease with which PBPCs can be collected and their reproducible clinical effectiveness to support patients through intensive treatment protocols have led to a virtual elimination of bone marrow as the source of cellular support for myeloablative chemotherapy in many transplant centers. Novel investigative approaches are also possible with PBPCs. In this review, the historical background of PBPCs is summarized, and the potential benefits (including economic advantages) of PBPCs to support dose‐intensive chemotherapy for treating breast cancer are discussed. While dose intensification of breast cancer chemotherapy to the degree requiring PBPC support remains controversial and, in most centers, investigational, there is no doubt that PBPCs are an effective adjunct to the hematopoietic support of patients undergoing transplant‐level cytotoxic treatments. Further study will undoubtedly lead to increased use of PBPCs in novel treatments for patients with breast cancer and other solid tumors.
Hormonal Modulation of the Interactions of Cultured Rat Testicular Sertoli and Peritubular Myoid Cells
Authors: RAYCHOUDHURY SAMIR S. , BLACKSHAW ALAN W. , IRVING MICHAEL G.
Published: October 2023

ABSTRACT: Previous investigators have suggested metabolic cooperation between Sertoli and peritubular cells. This study concerns Sertoli cell and peritubular myoid cell interactions in terms of synthesis of one of the main testicular extracellular matrix (ECM) constituents, glycosaminoglycans (GAG). We have tested the effect of hormones and other regulatory agents such as a combination of FSH, insulin, retinol, and testosterone (FIRT) on monocultures of Sertoli and peritubular myoid cells, and have examined whether or not coculture of Sertoli and peritubular myoid cells substitutes for the stimulation by FIRT. Cocultures of Sertoli and testicular peritubular myoid cells showed significant increases in the levels of secreted protein and sulfoprotein, as well as in cell‐associated GAG synthesis in untreated cultures. This indicates cell‐cell cooperation between Sertoli and peritubular myoid cells in the testis in terms of sulfated protein and GAG synthesis. Addition of the hormone mixture and retinol (FIRT) stimulated cell‐associated and ECM‐associated GAG in peritubular myoid cells, suggesting a role of circulating hormones in ECM production by peritubular myoid cells in vivo. Cocultures of Sertoli and myoid cells substituted for the stimulatory response of FIRT on peritubular myoid cells, predominantly in terms of cell‐associated GAG synthesis, which again emphasizes that the paracrine regulation of testicular ECM synthesis is dependent on Sertoli‐myoid cell cooperation.
Impaired Secretory Function of the Prostate in Men With Oligo‐Asthenozoospermia
Authors: AHLGREN GÖRAN , RANNEVIK GUNNAR , LILJA HANS
Published: October 2023

ABSTRACT: The secretory function of the human prostate and the seminal vesicles is a prerequisite for gel formation and liquefaction of semen, but the relation to poor sperm motility and low sperm count in infertile men remains to be clarifyed. Our aim was to evaluate the secretory function of the prostate and the seminal vesicles in normozoospermic men (n=35) and in asthenozoospermic men, who were all also oligozoospermic (n=27). All 62 subjects belonged to couples undergoing routine infertility evaluation. In liquefied seminal fluid we measured the concentrations of fructose and protein C inhibitor (PCI) contributed by the seminal vesicles, PCI complexed to prostate‐specific antigen (PSA), and the prostatic contribution of zinc, PSA, acid phosphatase (PAP), β‐microseminoprotein (β‐MSP), and Znα2‐glycoprotein (Znα2‐GP). The concentration of each prostatic secretory protein correlated significantly with that of zinc (P < 0.01) in both the normozoospermic (NZS) and oligo‐astheno‐zoospermic (OAZS) subgroups, but the PCI concentration did not correlate significantly with that of fructose. There was no significant difference between the NZS and OAZS subgroups in ejaculate volume or secretory contribution from the seminal vesicles, whereas the OAZS subgroup was characterized by significantly lower secretory contributions of Znα2‐GP (P = 0.001), Zn, PSA, PAP (P < 0.01), and β‐MSP (P < 0.05). The two subgroups did not differ significantly in the serum concentration of luteinizing hormone (LH), testosterone, or sex hormone‐binding globulin (SHBG). The results thus suggest the secretory contribution of major prostatic proteins and zinc per ejaculate to be significantly decreased in oligo‐asthenozoospermic men. The importance of this finding in relation to poor sperm count and motility as indicators of impaired gonadal function requires further investigation.