bluuebunny/crossref_metadata_2025 huggingface dataset:
Electroreductive Deoxygenative C−H and C−C Bond Formation from Non‐Derivatized Alcohols Fueled by Anodic Borohydride Oxidation
Authors: Villo Piret , Lill Malin , Alsaman Zainab , Soto Kronberg Adrian , Chu Victoria , Ahumada Guillermo , Agarwala Hemlata , Ahlquist Mårten , Lundberg Helena
Published: October 2023

Alcohols are one of the most common organic compound classes among natural and synthetic products. Thus, methods for direct removal of C−OH groups without the need for wasteful pre‐functionalization are of great synthetic interest to unlock the full synthetic potential of the compound class. Herein, electroreductive C−OH bond activation and subsequent deoxygenative C−H and C−C bond formation of benzylic and propargylic alcohols are demonstrated along with mechanistic insights. Experimental and theoretical studies indicate that the reductive C−OH bond cleavage furnishes an open shell intermediate that undergoes a radical‐polar crossover to the corresponding carbanion that subsequently undergoes protonation to furnish alkane products. Furthermore, we demonstrate that the carbanion can be trapped with CO2 to form arylacetic acids. The cathodic transformations are efficiently balanced by the anodic oxidation of sub‐stoichiometric borohydride additives, a strategy that serves as a highly attractive alternative to the use of sacrificial metal anodes.
Scalable Production of Separator and Cathode Suspensions via Extrusion for Sulfidic Solid‐State Batteries
Authors: Batzer Mattis , Gundlach Daniel , Michalowski Peter , Kwade Arno
Published: October 2023

Due to their high ionic conductivity, sulfidic solid electrolytes are considered to have great potential as a key element of solid‐state batteries. Such batteries could offer safety, thermal stability, and high energy densities. A key requirement is the scalable production of separators and electrodes, taking into account the high demands the moisture‐sensitive material imposes on the surrounding atmosphere. Therefore, in this publication we will demonstrate the establishment of an extrusion process under argon atmosphere for the continuous production of separator and cathode suspensions. After systematically investigating the influence of the process parameters speed, temperature and mass flow on the adhesive strength, ionic conductivity and capacity, the obtained knowledge is used for the fabrication of improved layers. The Li3PS4 based separators show a comparatively high ionic conductivity of 0.036 mS cm−1 (conductivity of pure solid electrolyte: 0.05 mS cm−1), the cells reach specific capacities of up to 156 mAh g−1 in the 1st cycle.
Creating Hydrophobic Foils From Biopolymer Blends Using Mechanical Microimprinting
Authors: Liu Hang , Zagler Michaela , Nase Michael , Weber Katharina , Albrecht Joachim
Published: October 2023

The front cover artwork is provided by Hang Liu from Prof. Dr. Joachim Albrecht's and Prof. Dr. Katharina Weber's group at Aalen University. The image depicts the wetting properties of a biopolymer foil. Surface microstructuring allows the tailoring of physical chemical properties that can lead to biodegradable packaging foils. Read the full text of the Research Article at 10.1002/cphc.202300301.
Deep Eutectic Solvents: An Eco‐friendly Design for Drug Engineering
Authors: Oyoun Feras , Toncheva Antoniya , Henríquez Luis Castillo , Grougnet Raphael , Laoutid Fouad , Mignet Nathalie , Alhareth Khair , Corvis Yohann
Published: October 2023

Invited for this month′s cover, the researchers from UTCBS and CiTCoM from Université Paris Cité (Paris, France), as well as Materia Nova (Mons, Belgium). The image emphasizes the deep eutectic solvent preparation thanks to hydrogen bond acceptor and donor interactions for drugs formulation and therapeutic applications. The Review itself is available at 10.1002/cssc.202300669.
Effectiveness of web‐based guided self‐help cognitive behavioral therapy‐enhanced for binge‐eating disorder: An implementation study
Authors: Melisse Bernou , van den Berg Elske , de Beurs Edwin
Published: October 2023

Introduction

Web‐based guided self‐help cognitive behavioral therapy‐enhanced (CBT‐E) is a 12‐weeks, 12‐sessions, digitalized version of part II of the self‐help book Overcoming Binge Eating. This intervention is effective when offered under controlled circumstances in a randomized‐controlled‐trial. It is unknown how patients with binge‐eating disorder (BED) respond to this intervention when offered in real‐world clinical‐settings. The aim of this study is to examine post‐intervention effectiveness of guided self‐help CBT‐E for BED in real‐world settings.

Method

The present study used a cohort‐design examining the effectiveness of web‐based guided self‐help CBT‐E according to an intention‐to‐treat (ITT) analysis. BED patients (n = 278) were assessed pre‐ and post‐intervention. The primary outcome was reduction in binge‐eating episodes. Other outcomes were full‐recovery (EDE‐Q score <2.77 and abstinence from binge‐eating episodes), impaired psychosocial functioning, defined as secondary impairment, and general psychopathology post‐intervention.

Results

The number of binge‐eating episodes reduced by an average of 16 binge‐eating episodes per 4 weeks pre‐intervention to five binge‐eating episodes during the last 4 weeks of treatment. Abstinence from binge eating was reported by 30%, and 28% reported full recovery. Effect sizes (Cohen's d) were large (d ≥ 1.0) for all outcome measures. There were no differences in outcomes between the ITT and the completers sample.

Discussion

Guided self‐help CBT‐E is associated with significant improvements. The effects of guided self‐help CBT‐E offered in a real‐world‐setting are comparable to self‐help CBT‐E offered in a randomized‐controlled‐trial. However, it should be noted that comparisons with randomized‐controlled‐trials requires caution. Longer‐term follow‐up data are necessary to measure persistence of treatment benefits.

Public Significance

Offering CBT‐E as a web‐based guided self‐help intervention has several benefits for patients with BED. Guided self‐help CBT‐E is associated with significant improvements on the short term when offered in real‐world clinical settings.
High‐resolution data are necessary to understand the effects of climate on plant population dynamics of a forest herb
Authors: Christiansen Ditte M. , Römer Gesa , Dahlgren Johan P. , Borg Malin , Jones Owen R. , Merinero Sonia , Hylander Kristoffer , Ehrlén Johan
Published: October 2023

Climate is assumed to strongly influence species distribution and abundance. Although the performance of many organisms is influenced by the climate in their immediate proximity, the climate data used to model their distributions often have a coarse spatial resolution. This is problematic because the local climate experienced by individuals might deviate substantially from the regional average. This problem is likely to be particularly important for sessile organisms like plants and in environments where small‐scale variation in climate is large. To quantify the effect of local temperature on vital rates and population growth rates, we used temperature values measured at the local scale (in situ logger measures) and integral projection models with demographic data from 37 populations of the forest herb Lathyrus vernus across a wide latitudinal gradient in Sweden. To assess how the spatial resolution of temperature data influences assessments of climate effects, we compared effects from models using local data with models using regionally aggregated temperature data at several spatial resolutions (≥1 km). Using local temperature data, we found that spring frost reduced the asymptotic population growth rate in the first of two annual transitions and influenced survival in both transitions. Only one of the four regional estimates showed a similar negative effect of spring frost on population growth rate. Our results for a perennial forest herb show that analyses using regionally aggregated data often fail to identify the effects of climate on population dynamics. This emphasizes the importance of using organism‐relevant estimates of climate when examining effects on individual performance and population dynamics, as well as when modeling species distributions. For sessile organisms that experience the environment over small spatial scales, this will require climate data at high spatial resolutions.
Investigation on risk fields assessment in the longwall working face with single side roof cutting along the gob
Authors: Min Rui , Liu Jinzhao , Chen Xiangjun , Wang Lin
Published: October 2023

The number of mines using roof cutting and pressure relief technology to extract mine deep coal resources is increasing daily. Most of these mines are facing the risk of high gas emission and residual coal spontaneous combustion disasters, and the composite disasters caused by these two risks also threaten the safety of mine production. On the basis of constructing a model for the evolution of porosity and permeability in a single side roof cutting along the gob, this study studied the occurrence locations of gas explosion risk areas, oxidation and heating risk areas, and composite disaster areas under different air supply and gas emission conditions, and summarized the evolution laws of composite disaster risk areas. The research results show that the roof rock collapse caused by roof cutting and pressure relief technology reduces the permeability of porous medium, which significantly reduces the sensitivity of the width of the oxidation temperature rise zone and the composite disaster area to the air supply. The increase in air supply causes the position of the composite disaster risk zone inside the goaf to shift toward the deep part of the goaf, while the width remains basically unchanged. The increase in gas emissions has suppressed the occurrence of coal spontaneous combustion in the goaf, while also keeping the gas concentration in a large area outside the upper limit of gas explosion. The research content enriches the research system of gas and oxygen flow fields in the goaf cutting face, and has positive significance for the promotion and application of goaf cutting technology and the understanding of secondary disasters caused by it.
Novel approaches for lemon grass essential oil extraction: Ultrasound sonication and sparger‐based microwave assisted extraction as a combined technique
Authors: Dhotre Irsha , Sathe Vivek
Published: October 2023

The utilization of essential oils spans across various industries, encompassing food, pharmaceuticals, and cosmetics. Lemongrass, an herb renowned for its high essential oil content, was the focal point of this research. The objective was to explore a novel approach to extract essential oil from lemongrass by employing ultrasonic sparger‐based microwave‐assisted extraction (U Sp‐MAE) coupled with ultrasound sonicator pretreatment. The findings revealed that the application of the U Sp‐MAE technique, combined with ultrasound sonicator pretreatment, resulted in a significant increase in lemongrass essential oil yield. At a mixing ratio of 80 g of chopped lemongrass per 500 mL of deionized water, a remarkable yield of 1.87% was achieved. This study demonstrates the potential of the U Sp‐MAE technique, with ultrasound sonicator pretreatment, as a promising and efficient method for extracting essential oil from lemongrass. Furthermore, its potential applications extend to industrial settings, offering new avenues for utilization.
Sustainable Production Insight Through LCA and LCC Analysis of Injection Overmolded Structural Electronics Manufactured through Roll‐to‐Roll Processes
Authors: Räikkönen Minna , Sokka Laura , Hepo‐oja Lotta , Nordman Sirpa , Kraft Thomas M.
Published: October 2023

Printed electronics (PE) have provided new material and application opportunities for devices and systems as well as new manufacturing routes that all need to be considered for commercialization. This paper introduces a case study with universally relevant manufacturing processes and applications in the PE area, focusing on the Life Cycle Assessment (LCA) and Life Cycle Costing (LCC) of the Personal Activity Monitor (PAM) device. In the study, the PAM device's most important costs and environmental impacts during the prototype pilot production and device use phases are identified and assessed. Additionally, the potential environmental impacts of post‐consumption scenarios are considered. The LCA results indicate that the roll‐to‐roll (R2R) assembly of electronics and the R2R injection over‐molding are generally the most prominent production process steps affecting the results. From the LCC perspective, the capitial expenditure (CAPEX) contributor is the R2R assembly pilot line, due to its high investment cost and long operating time compare to other production assets. The traditional electronic components are the major operating expenditures (OPEX), especially the microcontroller units (MCUs) and accelerometers, in contrast to the low impact from the printed electronics. There are several advantages to applying LCA and LCC since they provide explanations of the relationships between cost, environmental, design, and manufacturing characteristics.
Hepatic Failure Associated with Imipramine Therapy
Authors: Shaefer Mark S. , Edmunds Ann L. , Markin Rodney S. , Wood R. Patrick , Pillen Todd J. , Shaw Byers W.
Published: October 2023

Imipramine, a widely used antidepressant, has rarely been associated with hepatic abnormalities. In the majority of reported cases, hepatic effects have been transient and readily reversible on discontinuation of the drug. We cared for an 11‐year‐old boy with hepatic failure and massive cell necrosis which followed treatment with imipramine for enuresis. This therapy led to fulminant hepatic failure and subsequent liver transplantation.
Home Monitoring of Theophylline Levels: A Novel Therapeutic Approach
Authors: Chandler Mary H.H. , Clifton G. Dennis , Louis Bettina A. , Coons Stephen Joel , Foster Thomas S. , Phillips Barbara A.
Published: October 2023

This pilot clinical investigation was conducted to compare a home therapeutic drug‐monitoring (TDM) method for theophylline blood levels and a traditional TDM method with respect to various patient outcome factors. Outpatients with chronic obstructive pulmonary disease (COPD) or asthma who were receiving long‐term theophylline therapy were randomized to one of two groups: home TDM or traditional TDM (controls). Patients in the former group monitored their serum theophylline levels at home over 6 months. Patients in both groups completed survey instruments, including questionnaires, visual analog scales, and other psychosocial measures, at designated times throughout the study period. Pulmonary function tests and dyspnea index scores were evaluated at each clinic visit. Results indicated a significantly lower (p < 0.05) number of changes in concomitant drug therapy in the home TDM group compared with controls. Other indicators that showed a trend toward more favorable outcomes in the home TDM group included symptomology, percentage of levels within the therapeutic range, patient attitudes regarding participation in health care management, and pulmonary function test results. Home monitoring prevented unnecessary clinic visits in several instances when theophylline dosage adjustments were based on telephone reports from patients. The utility of a home TDM method for theophylline has not been reported previously despite potential for broad applications. Findings from this preliminary study may support the use and feasibility of state‐of‐the‐art methodologies in carefully selected subpopulations outside the confines of the hospital or clinic setting.
Pharmacokinetics of Fluconazole in Serum and Cerebrospinal Fluid in a Patient with AIDS and Cryptococcal Meningitis
Authors: Chin Tom , Fong I. W. , Vandenbroucke A.
Published: October 2023

The detailed pharmacokinetics of fluconazole in serum and cerebrospinal fluid (CSF) were studied in a patient with acquired immunodeficiency syndrome and cryptococcal meningitis, after an intravenous dose of 400 mg. Fluconazole exhibited a serum elimination half‐life of 34.2 hours, distribution volume of 0.56 17kg, and clearance of 0.19 ml/min/kg. Peak CSF concentration occurred at 4 hours after the dose. Overall penetration of fluconazole based on the ratio of areas under the curve of CSF to serum was 70%. The drug exhibited an excellent pharmacokinetic profile for treatment of central nervous system fungal infections.
Prospective Surveillance of Intravenous Amphotericin B Use Patterns
Authors: Grasela Thaddeus H. , Goodwin S. Diane , Walawander Mary K. , Cramer Richard L. , Fuhs David W. , Moriarty Veronica P.
Published: October 2023

Information on amphotericin B use patterns and infusion‐related adverse events were prospectively collected from 397 hospitalized adults. The methods of initiating amphotericin B varied greatly, with the majority of patients being gradually titrated to a full maintenance dose over 1–5 days. Overall, 71% of patients experienced at least one episode of an infusion‐related adverse event (IRAE) during the first week of therapy. Fever and chills were most commonly observed, with peak frequency on days 1 −3, followed by a subsquent decline. A wide variety of pretreatment medications were used to minimize IRAE; the most common regimens included some combination of diphenhydramine, acetaminophen, and corticosteroids, with or without heparin. The majority of patients (84.7%) received a test dose, and although none experienced a severe allergic reaction, one patient subsequently had an anaphylactic episode on the third day of amphotericin B therapy. The use of a test dose and the titration process are attempts to avoid the IRAE frequency associated with large initial doses of amphotericin B, but we observed that they provided little or no benefit. In addition, our study suggests that pretreatment regimens are frequently used in conjunction with the test dose. If the intent of the test dose is to identify patients sensitive to amphotericin B, pretreatment drugs may minimize these adverse events and prevent a complete evaluation of response to the test dose.
Effect of Glycated Albumin on Phenytoin Binding in Elderly Patients with Type II Diabetes Mellitus
Authors: Kostic Barbara A. P. , Olsen Keith M. , Kearns Gregory L. , Kemp Stephen F.
Published: October 2023

We evaluated the effect of glycated albumin on phenytoin protein binding in 36 elderly (age range 63–94 yrs) patients with type II diabetes mellitus (DM) under diet management. Serum was spiked with 15 mg/L phenytoin and incubated. A serum ultrafiltrate was obtained from each sample for determining total and free phenytoin concentrations. Glycated hemoglobin was determined by boronate‐affinity chromatography, and glycated albumin was separated from nonglycated fractions with boronate‐agarose gel. Glycated hemoglobin in the study group ranged from 4.3–14.6% (mean 7.8 ± SD 2.1%) and glycated albumin ranged from 3.7–12.5% (7.4 ± SD 2.6%). We observed no correlation between glycated albumin and the percentage of free phenytoin (r2 = −0.14; p = 0.419). The concentration of nonglycated albumin ranged from 0.66‐4.28 g/dl (mean 3.45 ± 0.67 g/dl) and was calculated from measured total and glycated albumin concentrations. A correlation between the free fraction of phenytoin and nonglycated albumin was not demonstrated (r2 = 0.22, p = 0.22). In addition, a correlation was not observed between total glycated albumin and the free fraction of phenytoin (r2 = −0.095; p = 0.58). We conclude that elderly patients with type II DM under diet control do not have significant alterations in phenytoin protein binding. The use of total serum phenytoin levels therefore appears appropriate for determining phenytoin dosages in elderly patients with well controlled type II DM.
The Effect of Tourniquet Inflation on Cefazolin Tissue Penetration During Total Knee Arthroplasty
Authors: Friedrich Lawrence V. , White Roger L. , Brundage Dianne M. , Kays Michael B. , Friedman Richard J.
Published: October 2023

Patients undergoing total knee arthroplasty were randomized to tourniquet inflation 1, 2, or 5 minutes after a 1‐g dose of cefazolin. Serum, soft tissue, and bone samples were obtained at 10, 30, and 60 minutes after inflation, immediately prior to tourniquet release (PTR), and 5 minutes after release. Areas under the concentration‐time curve (AUC10‐PTR) were calculated using the linear trapezoidal method and normalized to actual body weight, creatinine clearance, and length of tourniquet inflation. The percentage of penetration was calculated using the normalized values for the respective AUCs. Differences among the groups were analyzed using analysis of variance or the Kruskal‐Wallis test where appropriate. Groups were similar for age, actual body weight, duration of tourniquet inflation, and creatinine clearance (p > 0.05). The median percentages of penetration for soft tissue and bone at 5, 2, and 1 minute were 14.5% and 4.6%, 6.7% and 3.0%, and 5.9% and 4.6%, respectively. Only the percentage of soft tissue penetration between 5 and 1 minute was significantly different (p = 0.015). Gender and type of anesthesia (general, epidural) had no effect on cefazolin penetration into soft tissue or bone. Although increasing the time interval between cefazolin administration and tourniquet inflation resulted in higher soft tissue drug concentrations, a 1 ‐ minute interval resulted in soft tissue and bone cefazolin concentrations at or above the minimum inhibitory concentration for microorganisms likely to be encountered in this surgical procedure.
Limited Effectiveness of Charcoal Hemoperfusion in Malathion Poisoning
Authors: Burgess Ellen D. , Audette Robert J.
Published: October 2023

Malathion is an organophosphate pesticide that can cause respiratory failure and death in humans. In vitro studies suggested that hemoperfusion may be valuable in treating malathion poisoning. We found that although the charcoal column may effect reasonable clearance in the first 2 hours of use, prolonged hemoperfusion may require changing the column in severe, acute poisonings.
Analgesic Efficacy and Safety of Single‐Dose Oral and Intramuscular Ketorolac Tromethamine for Postoperative Pain
Authors: Brown Colin R. , Moodie John E. , Dickie Gay , Wild Vicki M. , Smith Barbara A. , Clarke Peter J. , Evans Stephen A. , Bynum Lincoln J.
Published: October 2023

The efficacy and safety of the analgesic drug ketorolac tromethamine in the treatment of moderate to very severe postoperative pain was assessed in five dose‐ranging studies with single‐dose, double‐blind, randomized, parallel‐group designs. The drug was administered orally (2.5–200 mg, 352 patients in three trials) and intramuscularly (5–90 mg, 395 patients in two trials), and compared with placebo and reference drugs. Patients subjectively evaluated pain intensity and relief using verbal categoric and visual analog scales; efficacy values included pain intensity difference (PID), summed PID, and total pain relief. Oral ketorolac 10, 12.5, 100, and 200 mg were each statistically significantly superior to placebo in all efficacy measurements, and 10 mg was equivalent to intramuscular morphine 10 mg. Intramuscular ketorolac 90 mg was superior to and 10 and 30 mg were similar to intramuscular morphine 12 mg, and all of these ketorolac doses were superior to intramuscular morphine 6 mg. Intramuscular ketorolac 10 and 30 mg were superior to intramuscular meperidine 50 and 100 mg. Ketorolac was well tolerated, with rates of adverse events generally lower than those of the opiate comparators. Ketorolac doses of 2.5 and 5 mg were less effective than higher doses; 10 mg or more resulted in faster onset of action and greater peak efficacy; 90 mg or more gave more prolonged analgesic effects.
Candidal Urinary Tract Infections: A Comprehensive Review of Their Diagnosis and Management
Authors: Gubbins Paul O. , Piscitelli Stephen C. , Danziger Larry H.
Published: October 2023

Despite its prevalence, the significance of candiduria remains uncertain. The pathogenesis of candidal urinary tract infections has been relatively well characterized and many risk factors have been identified. The disorders lack consistent diagnostic criteria, however, such as the presence of pyuria or a colony count above which is predicative of presence, location, or severity of infection. Treatment is unclear due to lack of data defining the natural progression of the disease. Although often recommended, it may not always be possible to remove risk factors. Amphotericin B, fluconazole, 5‐flucytosine, and other antifungal agents are important agents for managing candidal urinary tract infections.
Renovascular Effects of Nonprescription Ibuprofen in Elderly Hypertensive Patients With Mild Renal Impairment
Authors: Furey Sandy A. , Vargas Ramon , McMahon F. Gilbert
Published: October 2023

To determine the renovascular effects of nonprescription ibuprofen in the maximum labeled over‐the‐counter (OTC) dosage for 7 days, and to compare these effects with those of two other available OTC analgesics, aspirin and acetaminophen, we evaluated 25 elderly patients with mild thiazide‐treated hypertension and mild renal insufficiency. Under double‐blind conditions, patients were randomly allocated to one of three treatment groups: ibuprofen 400 mg 3 times/day, aspirin 650 mg 3 times/day, or acetaminophen 650 mg 3 times/day. Blood pressure and indexes of renal function (blood urea nitrogen, creatinine clearance, serum electrolytes) were measured over 7 days in a clinical research center. None of the treatments had a clinically significant effect on blood pressure. Renal function indexes also remained unchanged during all three treatments. We conclude that elderly patients with mild thiazide‐treated hypertension and mild renal insufficiency seem not to be at risk of developing additional renal compromise or of having their hypertension control diminished by treatment with these OTC analgesics for 7 days.
Can Garlic Lower Blood Pressure? A Pilot Study
Authors: McMahon F. Gilbert , Vargas Ramon
Published: October 2023

A popular garlic preparation containing 1.3% allicin at a large dose (2400 mg) was evaluated in this open‐label study in nine patients with rather severe hypertension (diastolic blood pressure ≥ 115 mm Hg). Sitting blood pressure fell 7/16 (± 3/2 SD) mm Hg at peak effect approximately 5 hours after the dose, with a significant decrease in diastolic blood pressure (p<0.05) from 5–14 hours after the dose. No significant side effects were reported. Our results indicate that this garlic preparation can reduce blood pressure. Further controlled studies are needed, particularly with more conventional doses (e.g., ≤ 900 mg/day), in patients with mild to moderate hypertension and under placebo‐controlled, double‐blind conditions.
The Pharmacology of α‐Adrenergic Decongestants
Authors: Johnson David A. , Hricik Joseph G.
Published: October 2023

The mechanism by which decongestants produce their action is activation of postjunctional α‐adrenergic receptors found on precapillary and postcapillary blood vessels of the nasal mucosa. Activation of these receptors by either direct binding of the sympathomimetic agent to the binding site of the receptor, or by the enhanced release of norepinephrine produces vasoconstriction. Such vasoconstriction decreases blood flow through the nasal mucosa and results in shrinkage of this tissue. Decongestants can be administered topically, directly onto the nasal mucosa, or orally. Prolonged topical administration may produce rebound congestion. Oral decongestants can affect the cardiovascular, urinary, central nervous, and endocrine systems. Overdose can produce medically significant increases in blood pressure as well as central nervous system stimulation.
Neglected Pathogens: Bacterial Infections in Persons With Human Immunodeficiency Virus Infection A Review of the Literature (First of Two Parts)
Authors: Fish Douglas N. , Danziger Larry H.
Published: October 2023

Bacterial infections, including those that cause infection in the healthy host as well as those that are more opportunistic, occur very commonly among persons infected with the human immunodeficiency virus (HIV). Bacterial infections are a direct result of the severe humoral and cellular immune defects found in these patients. Epidemiologic factors such as intravenous drug use and stage of HIV infection may also play important roles. Pulmonary, bloodstream, gastrointestinal, central nervous system, skin and soft tissue, and catheter‐related infections are common, as are endocarditis, prostatitis, and others. Frequently reported pathogens are common organisms such as Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae, and enteric gram‐negative pathogens, as well as less typical ones such as Listeria monocytogenes and Nocardia sp. The frequency of infection is specific to organ system and pathogen, often being many times higher than in immunocompetent hosts. Prompt recognition and aggressive therapy are required to reduce morbidity and mortality due to these infections.
A Follow‐Up Safety Study of Ciprofloxacin Users
Authors: Jick Susan S. , Jick Hershel , Dean Alan D.
Published: October 2023

We followed 37,233 outpatients for 45 days after receiving a prescription for ciprofloxacin to identify any newly diagnosed, important illnesses that might have been caused by the drug. For 29 users the role of ciprofloxacin in the etiology of the illness could not be confidently ruled out (7.79/10,000 persons; 95% CI 5.42‐11.18). In only seven was a causal relation to ciprofloxacin considered likely: three skin reactions and one case each of thrombocytopenia, “headache, nausea, and shakes,” hallucinations, and palpitations. No fatal illnesses occurred, and all patients recovered after discontinuing the drug. In addition, few cases of photosensitivity were associated with the agent. We conclude that important adverse reactions attributable to ciprofloxacin are uncommon.
Possible Interaction Between Warfarin and Fluconazole
Authors: Gericke Kristin R.
Published: October 2023

Fluconazole is a triazole antifungal agent reported to have a low affinity for human cytochrome P‐450, and thus would not be expected to interact with drugs metabolized through the cytochrome P‐450 system, including phenytoin, cyclosporine, and warfarin. A potential interaction between warfarin and fluconazole occurred in a 39‐year‐old man with chronic renal insufficiency. He was receiving anticoagulant therapy for a lower extremity thrombus and oral fluconazole 50 mg/day for a fungal urinary tract infection. After attaining consistent international normalized ratio (INR) values between 2.0 and 2.7 with warfarin, the INR increased to 5.2 four days after fluconazole was started, despite decreasing the dosage of warfarin. There were no changes in the patient's other medications, and the INR decreased to 1.5 on discontinuation of fluconazole. The possible mechanism of an interaction may be dose‐related inhibition of warfarin metabolism, and may be more pronounced in patients with decreased renal clearance of fluconazole.
Development of Resistance During Antimicrobial Therapy: A Review of Antibiotic Classes and Patient Characteristics in 173 Studies
Authors: Fish Douglas N. , Piscitelli Stephen C. , Danziger Larry H.
Published: October 2023

The incidence of emergent resistance and clinical factors affecting its development were evaluated by retrospective review of 173 studies encompassing over 14,000 patients. Eight antibiotic classes and 225 individual treatment regimens were evaluated. Emergent resistance occurred among 4.0% of all organisms and 5.6% of all infections treated. It appeared to be significantly more frequent with penicillin and aminoglycoside monotherapy, with significantly lower rates associated with imipenem‐cilastatin, aztreonam, and combination therapy. Clinical failure also appeared to be significantly more likely to occur after emergence of resistance among organisms treated with fluoroquinolones or aminoglycosides. Infections associated with higher resistance rates were cystic fibrosis, osteomyelitis, and lower respiratory tract infections. Resistance was most common in patients in intensive care units or receiving mechanical ventilation. It was also significantly frequent among studies performed in university or teaching hospitals. Organisms associated with high resistance rates were Pseudomonas aeruginosa, Serratia, Enterobacter, and Acinetobacter sp. Factors such as infection type, underlying diseases, type of institution, and specific pathogens warrant consideration when examining emergent resistance.
Application of Flow Cytometry to Studies on the Human Acrosome
Authors: PURVIS KENNETH , RUI HALLGEIR , SCHØLBERG AASA , HESLA SJUR , CLAUSEN OLE PETTER F.
Published: October 2023

This study describes the use of flow cytometry combined with specific labelling of the human sperm acrosome using a FITC‐labelled plant lectin (Arachis hypogea agglutinin). Localization of the label to the acrosome was encouraged by freezing the sperm for at least 24 hours at −70°C prior to labelling. Studies of sperm from 53 normospermic men revealed that acrosome labelling followed a single normal distribution without the presence of subpopulations. The average fluorescence and degree of variation within the sperm population differed markedly between sperm samples. These differences could not be predicted by any of the normal criteria of sperm quality, including sperm morphology, vitality, and motility. Exposure of washed sperm to the calcium ionophore A 23187 in the presence of calcium at 37°C, caused a time‐related leftward shift in the distribution of acrosome fluorescence, indicating that this technique can be also used to monitor the acrosome reaction.
Characterization of Functional Leydig Cells after Purification on a Continuous Gradient of Percoll
Authors: BROWNE ELIZABETH S. , SOHAL GURKIRPAL S. , BHALLA VINOD K.
Published: October 2023

Two human chorionic gonadotropin (hCG) responsive cells from rat testicular interstitium were previously isolated on a discontinuous gradient of Percoll. The light cells were non‐steroidogenic and bound125I‐labeled hCG with high affinity (Kd3.0 × 10−10mol/L), whereas the steroidogenic heavier cells (Leydig cells) produced cyclic adenosine monophosphate (cAMP) and testosterone in response to hCG stimulation with very little hCG binding. In that study, the heavier cell fraction was contaminated with germ cells, red blood cells, and other cells. These cells have now been further purified on a continuous gradient of Percoll (20 to 60%, v/v), and have resolved into three visible bands. The cells in subtraction I, predominantly damaged Leydig cells, germ cells, and/or residual light cells, bind125I‐labeled hCG with high affinity (Kd4.09 × 10−10mol/L) without producing cAMP and testosterone in response to hCG. Subtraction III consists mainly of red blood cells. The cells in subtraction II, identified as typical Leydig cells by electron microscopy, produce cAMP and testosterone in response to hCG but, again, bind only a small amount of hCG (4.5 ± 0.3 fmol/2 × 106cells/250 μl/per hour at 37° C). Thus, further purification of the heavier cell fraction from a discontinuous gradient of Percoll on a continuous gradient of Percoll yields Leydig cells, free of contaminating germ cells and red blood cells, which actively produce cAMP and testosterone with a very low level of hCG binding, the affinity of which is undetectable by current binding techniques.
Long‐Term Outcome Following Testicular Ischemia in the Rat
Authors: STERN JOHN A. , LUI RAPHAEL C. , LaREGINA MARIE C. , HERBOLD DAVID R. , TOLMAN KIM C. , JOHNSON FRANK E.
Published: October 2023

Male germ cells are quite sensitive to interruption in blood flow. Eight weeks after subjection to 45 minutes of testicular ischemia, the spermatogenic epithelium of the rat remains significantly damaged, though other cell types are well preserved. The authors evaluated the testicular recovery of the rats at 8 and 72 weeks after the 45‐minute period of warm ischemia. Twenty‐eight rats were studied: 14 underwent 45 minutes of total left testicular ischemia; 14 received no treatment. Four rats from each group were necropsied at S weeks to document the ischemic injury. At 72 weeks, the 18 surviving rats were necropsied to evaluate the long‐term outcome of the treatment. At 8 weeks, significant left testicular injury was documented. However, at 72 weeks there was no difference in testicular weight or sperm head count between the groups: in all 36 testicles, the repopulation index was 1.00, the epididymal index was 3+, the modified Johnsen index was 14, and the spermatic cord score was 7 (all are maximum obtainable scores). Neither contralateral orchiopathy nor injury to spermatic cord structures was observed. Our work shows that ischemia‐induced testicular injury is fully reversible with time in this model.
Acute and Chronic Effects of Cisplatinum upon Testicular Function in the Rat
Authors: HUANG HOSEA F. S. , POGACH LEONARD M. , NATHAN ESWARI , GIGLIO WILLIAM
Published: October 2023

One of the side effects of cisplatinum‐based chemotherapy is the impairment of spermatogenic function. In order to understand the mechanisms responsible for this side effect, the present study examined the short‐and long‐term effects of five daily injections of 2 mg/kg cisplatinum upon the functional normality of Leydig cells and Sertoli cells in intact adult rats, and their relationship with the status of spermatogenesis. Results of the present study demonstrate that cisplatinum treatment resulted in a progressive but reversible loss of germ cells from the seminiferous epithelium. Although testicular testosterone contents reduced transiently after the administration of cisplatinum, these testosterone levels are otherwise sufficient to support complete spermatogenesis. Thus, the cisplatinum‐induced germinal regression cannot be accounted for by hypoandrogenism. The testicular ABP contents of the drug‐treated rats remained unchanged during the treatment period, decreased transiently 30 days after the treatment, and returned to normal 120 days after treatment. A decrease in epididymal ABP content was also noted 10 and 30 days after the drug treatment. These observations suggest that Sertoli cell functions were affected by cisplatinum treatment. The effects of cisplatinum upon Sertoli cells were further demonstrated by the dose‐dependent suppression of the production of ABP, lactate, and estradiol in cultured Sertoli cells. In addition, cisplatinum administration resulted in a reversible decrease in pituitary weights and an irreversible decrease in seminal vesicle weights. These results further demonstrate the toxic effects of cisplatinum upon various aspects of the male reproductive system.
A Comparison of Two Computer‐Automated Semen Analysis Instruments for the Evaluation of Sperm Motion Characteristics in the Stallion
Authors: JASKO DAVID J. , LEIN DONALD H. , FOOTE ROBERT H.
Published: October 2023

Two commercially available computer‐automated semen analysis instruments (CellSoft Automated Semen Analyzer and HTM‐2000 Motion Analyzer) were compared for their ability to report similar results based on the analysis of pre‐recorded video tapes of extended, motile stallion semen. The determinations of the percentage of motile cells by these instruments were more similar than the comparisons between subjective estimates and either instrument. However, mean values obtained from the same sample may still differ by as much as 30 percentage units between instruments. Instruments varied with regard to the determinations of mean sperm curvilinear velocity and sperm concentration, but mean sperm linearity determinations were similar between the instruments. We concluded that the determinations of sperm motion characteristics by subjective estimation, CellSoft Automated Semen Analyzer, and HTM‐2000 Motility Analyzer are often dissimilar, making direct comparisons of results difficult.
Quantitative Maintenance of Spermatogenesis in Cyclosporine‐Treated Rats by Exogenous Administration of Testosterone Propionate
Authors: SEETHALAKSHMI L. , FLORES CARLOS , CARBONI A.A. , MENON M.
Published: October 2023

The authors had previously shown that the subcutaneous administration of cyclosporine (CsA) resulted in an impairment of spermatogenesis. Testosterone levels declined and gonadotropin levels increased, suggesting that CsA primarily affects the synthesis and secretion of testosterone. In this study, the authors attempted to determine whether the exogenous administration of testosterone would maintain spermatogenesis in animals treated with a very high dose of CsA. Sexually mature, male Sprague‐Dawley rats were treated subcutaneously with CsA (40 mg/kg per day) alone, or in combination with testosterone propionate (TP; 2 and 5 mg/d per rat), for 14 days. As expected, CsA reduced the body and reproductive organ weights and the levels of serum testosterone, while elevating the levels of follicle‐stimulating hormone (FSH) and luteinizing hormone (LH). Quantitative analysis of spermatogenesis revealed a decline in all the different types of germ cells in tubules at stage VII of the cycle of the seminiferous epithelium. Administration of TP in 2 and 5 mg/d per rat doses restored the body and reproductive organ weights and the circulating levels of FSH. The serum levels of LH were below the assay's minimum level of detectability. Analysis of spermatogenesis revealed a dose‐dependent increase in the germ cell counts after the administration of 2 and 5 mg of TP. The circulating levels of CsA were also significantly reduced after TP administration. These results revealed that CsA‐induced alteration in spermatogenesis can be prevented by the exogenous administration of testosterone.
Extracellular Tubules in Semen
Authors: WOLBURG HARTWIG , SCHIEFERSTEIN GEORG
Published: October 2023

Tubules were observed in the semen of two patients, one of whom was fertile. The tubules measured 75 to 90 nm in diameter and were extracellular. However, they frequently were found in amorphous material reminiscent of cell debris and in association with cells, most of which were immature. They did not show the typical trilaminar structure of biologic membranes. Their biochemical nature and significance are unknown.
Leydig Cell Cooperation In Vitro: Evidence for Communication Between Adult Rat Leydig Cells
Authors: HEDGER M.P. , EDDY E.M.
Published: October 2023

In short‐term incubations (32 C, 3 h) of purified adult rat Leydig cells, increasing the density from 5000 to 50,000 cells/16 mm diameter culture well caused a significant increase in human chorionic gonadotropin (hCG)‐stimulated testosterone secretion/cell. Density‐dependent stimulation was also observed under basal conditions and in the presence of dibutyryl cyclic adenosine monophosphate, luteinizing hormone‐releasing hormone, or 22‐hydroxy cholesterol. In contrast, increasing the incubation density of purified Leydig cells by addition of other testicular cells had no effect on basal or hCG‐stimulated testosterone secretion. hCG‐stimulated testosterone secretion by Leydig cells incubated at low density was also increased by addition of Leydig cell‐conditioned medium. This stimulatory activity was removed by charcoal extraction and by ultrafiltration (approximately 30 kDa cut‐off). The data indicate that Leydig cells cooperate by secretion of low molecular weight, cell‐specific stimulatory factors that support Leydig cell steroidogenesis in vitro, and may also play a role in regulating Leydig cell function in vivo.
Sperm Creatine Kinase Activity in Fertile and Infertile Oligospermic Men
Authors: HUSZAR GABOR , VIGUE LYNNE , CORRALES MARCELIA
Published: October 2023

The authors examined the value of sperm creatin‐kinase (CK) activity parameters to predict sperm fertilizing potential of oligospermic men. Two patient groups from our intrauterine insemination program were studied: fertile oligospermic (32 men/46 specimens) and infertile oligospermic (19 men/82 specimens). In the initial specimens, the CK activities were (mean + SEM IU CK/108 sperm): 0.53 ± 0.09 and 1.17 ± 0.19 (P < 0.001). The corresponding values in the swim‐up fractions were 0.32 ± 0.06 and 0.67 ± 0.08 (P < 0.001). In a subset of samples by fertile (N = 33) and infertile (N = 66) oligospermic men who had close to identical sperm concentrations (11.9 ± 0.9 vs. 11.9 ± 0.5 million sperm/ml) and motility values (23.7 ± 1.7 vs. 23.0 ± 1.3%), the CK activities were significantly lower in the fertile group in both the initial (P = 0.02) and in the swim‐up (P = 0.002) samples. A logistic regression analysis of all 160 study samples (including 21 normal men/32 samples) further demonstrated that CK activities were predictive of fertilizing potential, whereas sperm concentrations of the samples provided no additional contribution. Sperm CK and similar biochemical markers will facilitate selection of men for various approaches in assisted reproduction.
Addition of Hypotaurine Can Reactivate Immotile Golden Hamster Spermatozoa
Authors: BOATMAN DOROTHY E. , BAVISTER BARRY D. , CRUZ ENDERSON
Published: October 2023

Hamster epididymal spermatozoa became virtually immotile following washing and dilution in chemically defined medium (TLP‐PVA). The sperm motility factors (penicillamine, hypotaurine, and epinephrine: PHE) were examined for their ability to reactivate immotile sperm. Sperm could be reactivated by addition of PHE at 1 h of incubation. Hypotaurine alone was capable of reactivating sperm motility, but epinephrine and penicillamine together were not. However, overall sperm motility and percentage of motile sperm during incubation were higher when PHE components were used in combination than when hypotaurine was used alone. Addition of hypotaurine to immotile sperm suspensions could be postponed for up to 6 h with subsequent recovery of sperm motility, although the degree of recovery of motility declined progressively with each hour that addition of hypotaurine was delayed. The rescuing effect of hypotaurine was due to an increase both in the percentage of motile sperm and in the quality (grade) of sperm motility. The data show that hypotaurine is required for expression of sperm motility in the hamster, and support the concept that the loss of hypotaurine from sperm following washing and dilution is responsible for the sperm‐immobilizing effect of these procedures. Additionally, the data demonstrate that hamster sperm can remain viable for several hours after becoming immotile, and that many of the immotile sperm are capable of being reactivated.