bluuebunny/crossref_metadata_2025 huggingface dataset:
Population and functional genomics of lactic acid bacteria, an important group of food microorganism: Current knowledge, challenges, and perspectives
Authors: Li Weicheng , Wu Qiong , Kwok Lai‐yu , Zhang Heping , Gan Renyou , Sun Zhihong
Published: October 2023

Lactic acid bacteria (LAB) are widely used in the food industry, but little is known about their population genomics, hindering our understanding of their genetic background and evolution. To better understand the evolution of LAB and their potential applications to related food production, we conducted a scoping review of the literature focusing on genomic issues related to LAB. The research progress of LAB population and functional genomics was summarized by sorting the literature of LAB genomics research in the last 10–15 years. According to the existing evidence, the formation mechanism of characteristics of LAB and their habitat adaptive evolution directed by genome decay and horizontal gene transfer were elucidated. The major evolutionary driving forces of LAB are mutations and horizontal gene transfer (HGT) events with or without the involvement of mobile genetic elements instead of recombination. We also underline the application of LAB genome in food safety and properties. Collectively, this review paper provides up‐to‐date information of the population and functional genomics of LAB, current challenges in the field, and suggestions for improving the exploitation and application of LAB resources.
Western diet strongly influences gut microbiomes in nursing rat dams but translates modest long‐term consequences to offspring modulated by leptin supplementation during suckling
Authors: Pomar Catalina A. , Viver Tomeu , Valle Ana , Gago Juan F , Castillo Pedro , Palou Mariona , Palou Andreu , Rossello‐Mora Ramon , Picó Catalina
Published: October 2023

Early life conditions may influence the gut microbiome and contribute to health status in adulthood. We examined the impact of maternal obesity and/or obesogenic diet on the gut microbiome of mothers (at weaning) and their adult offspring, along with the effects of leptin supplementation during suckling. Three groups of rats were studied: control (C) dams, fed with standard diet (SD); western diet (WD) dams, fed with WD (a high‐fat, high‐sucrose diet) before gestation and during gestation and lactation; and reversion (REV) dams, fed as WD‐dams but with SD during lactation. Offspring were supplemented throughout suckling with leptin/vehicle and weaned on an SD. WD‐dams showed lower microbial diversity and an altered microbiome compared to C‐ and REV‐dams, widely normalized by diet improvement during lactation. WD‐ and REV‐offspring (males) displayed lower microbiome diversity and greater dominance compared to C‐offspring. Taxonomic group differences (Proteobacteria phylum and Bacteroides, Parasutterella, and Phocea genera) were observed in WD‐ and REV‐offspring. WD‐offspring, but not REV‐offspring, had a greater abundance of the phylum Firmicutes and Lachnospiraceae family and a lower abundance of the family Tannerellaceae compared to C‐offspring. Leptin supplementation led to decreased abundance of the phylum Actinobacteria (family Eggerthellaceae and genera Enterorhabdus and Adlercreutzia (females)), and the genera Lachnospiraceae UCG‐008 group, Roseburia and Limosilactobacillus, and increased abundance of the genus Dellaglioa, compared to vehicle‐treated groups. Therefore, maternal consumption of an obesogenic diet during the perinatal period results in microbiome changes in dams, alleviated by dietary improvement during lactation. Maternal conditions and leptin supplementation during suckling modestly influenced the microbiome in adulthood, which might partially contribute to the adverse/beneficial effects, respectively, of these conditions on programmed metabolic health.
Impact of water loss on sustainability of the Mississippi River channel in its deltaic reach
Authors: Allison Mead A. , Meselhe Ehab A. , Kleiss Barbara A. , Duffy Sean M.
Published: October 2023

The Mississippi River channel from New Orleans to the Gulf of Mexico (GOM) is a key deep draft navigation channel and an active deltaic lobe. Natural and engineered lateral exits from this reach into adjacent receiving basins historically has provided mineral sediment for wetland accretion in the face of rising relative sea level and supported estuarine‐coastal food webs. However, our analysis indicates water losses from the channel have increased by 25% since 2004 due to (1) bank failures during large floods since 2012 that have created several large exit channels downriver of the flood protection levee, and (2) the opening of an engineered diversion at West Bay in 2004. This has resulted in a 60%–80% loss in stream power in the lowermost navigation channel that is accompanied by net shoaling between 2012 and 2022 and an increased dredging need. Our 2022 survey in the GOM exit passes indicates that only 20% of the freshwater, 5% of the total suspended sediment (2% of the sand) at New Orleans now reaches the GOM: this supports previous research indicating the delta front is retreating after centuries of progradation. Together these results indicate that (1) river containment and the sustainability of the navigation channel is threatened, (2) sediment load reaching the seaward end of the delta may be insufficient to avoid major degradation, and (3) the increased freshwater flux into adjacent shallow coastal water bodies has unknown implications for coastal hypoxia and food webs, including commercial species (e.g., oysters) and marine mammals. Future acceleration in sea level rise rates and tropical storm frequency/intensity would likely worsen these trends.
Replacement of watching television with physical activity and the change in gestational diabetes mellitus risk: A case–control study
Authors: Kouiti Malak , Lozano‐Lorca Macarena , Youlyouz‐Marfak Ibtissam , Mozas‐Moreno Juan , González‐Palacios Torres Carla , Olmedo‐Requena Rocío , Gea Alfredo , Jiménez‐Moleón José Juan
Published: October 2023

Objective

To evaluate the effect of replacing 1 h/week of watching television with 1 h/week of light to moderate (LMPA) or vigorous physical activity (VPA) before and during pregnancy on the risk of gestational diabetes mellitus (GDM).

Methods

A case–control study was conducted in pregnant women. Physical activity and television watching before and during pregnancy were assessed using the Paffenbarger Physical Activity Questionnaire. Each type of activity was classified according to intensity (metabolic equivalent of task; MET): less than 6 METs is LMPA, 6 METs or more is VPA. The duration of physical activity and watching television was calculated, and logistic regression models were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals for their association with GDM risk. The isotemporal substitution model was used to calculate the effect of replacing 1 h/week of watching television with the same duration of physical activity.

Results

The GDM cases (n = 290) spent less time performing VPA than controls without GDM (n = 1175) and more time watching television during pregnancy (P < 0.05). During pregnancy, the risk of GDM increased for each hour of watching television (aOR = 1.02; 95% confidence interval 1.00–1.03). Women who spent more time watching television during pregnancy were likely to develop GDM (aOR>14 h/week vs. 0–6 h/week = 2.03; 95% confidence interval 1.35–3.08). Replacing 1 h/week of watching television with 1 h/week of VPA during pregnancy could decrease the chance of developing GDM (aOR = 0.66; 95% confidence interval 0.43–1.00).

Conclusions

A simple change of 1 h/week of watching television for 1 h/week of VPA in pregnant women may reduce the risk of GDM considerably.
Propafenone‐Theophylline Interaction
Authors: Spinler Sarah A. , Gammaitoni Arnold , Charland Scott L. , Hurwitz Jodie
Published: October 2023

A 63‐year‐old man with ventricular tachycardia (VT) refractory to drug therapy was admitted for surgical ablation of the VT with coronary artery bypass graft surgery. He developed increased theophylline concentrations with decreased calculated theophylline clearance after propafenone therapy for recurrent VT was initiated. Within 1 day after the addition of propafenone 150 mg every 8 hours to a drug regimen that included theophylline sustained‐release tablets 300 mg every 12 hours, the patient demonstrated increased theophylline serum concentrations and decreased calculated theophylline clearance. Despite a decrease in theophylline dosage, theophylline concentrations continued to rise as the dosage of propafenone was increased to 300 mg every 8 hours. Theophylline was discontinued due to a rising theophylline level, improved oxygenation, and absence of wheezing. Both propafenone and theophylline are hepatically metabolized by the cytochrome P‐450 enzyme system. The decrease in theophylline clearance of 25% to 69% in this patient may be due to competitive metabolism resulting in enzyme inhibition and increased theophylline concentrations. Since propafenone and 5‐OH‐propafenone levels were not measured, it is unknown whether propafenone clearance was affected as well. Health care practitioners should be aware of this possible drug interaction and monitor theophylline concentrations and the electrocardiogram closely if the agents are coadministered.
The Effect of Cimetidine and Ranitidine Administration With Zidovudine
Authors: Fletcher Courtney V. , Henry W. Keith , Noormohamed Saleem E. , Rhame Frank S. , Balfour Henry H.
Published: October 2023

Study Objective. To evaluate the possibility of a drug interaction with zidovudine and histamine2‐receptor antagonists in individuals infected with the human immunodeficiency virus.

Design. Randomized crossover study.

Setting. University‐affiliated research center.

Patients. Six HIV‐infected individuals.

Interventions. The subjects received 7‐day regimens of zidovudine 600 mg/day alone, zidovudine with cimetidine 1200 mg/day, and zidovudine with ranitidine 300 mg/day.

Measurements and Main Results. The renal clearance of zidovudine when given alone was 0.41 L/kg/hour, and was reduced to 0.18 L/kg/hour (p=0.002) when given with cimetidine. In the presence of cimetidine the urinary excretion of zidovudine decreased from 89.5 to 53.7 μM (p=0.01), the urinary ratio of metabolite to parent increased from 5.16 to 9.96 (p=0.0001), and the fraction of zidovudine converted to metabolite increased from 0.86 to 0.92 (p=0.0025).

Conclusion. Cimetidine presumably inhibits the renal clearance of zidovudine by competing for tubular secretion. Based on the observation that neither cimetidine nor ranitidine had a significant effect on serum concentrations of zidovudine or zidovudine glucuronide, a change in the dosage of zidovudine is not warranted.
A Preliminary Study of Clarithromycin versus Doxycycline in the Treatment of Nongonococcal Urethritis and Mucopurulent Cervicitis
Authors: Stein Gary E. , Mummaw Nancy L. , Havlichek Daniel H.
Published: October 2023

In a comparison of drug safety and efficacy, 40 adult outpatients with clinical signs and symptoms of nongonococcal urethritis or mucopurulent cervicitis were treated with either clarithromycin 250 mg or doxycycline 100 mg twice/day for 7 days. Clinical and laboratory evaluations were repeated during, at the end, and 3 weeks after the completion of therapy. Isolation and susceptibility tests of Chlamydia and Mycoplasma isolates were performed at each visit. All but one patient who received doxycycline were clinically cured or improved at the end of treatment. Two (10%) patients who received clarithromycin and three (15%) who received doxycycline had clinical relapses of the infection. All isolates of Chlamydia trachomatis were eradicated and did not recur in both groups. Doxycycline was more effective than clarithromycin in eradicating Ureaplasma urealyticum (p<0.01). Both groups reported a high frequency of minor adverse effects, but no patient discontinued therapy. Overall, clarithromycin was clinically safe and effective treatment in patients with nongonococcal urethritis and mucopurulent cervicitis.
Effects of Sucralfate and Ranitidine on Aluminum Concentrations in Elderly Volunteers
Authors: Moore John G. , Coburn Jack W. , Sanders Michael C. , McSorley David J. , Sirgo Mark A.
Published: October 2023

Elevated aluminum concentrations have been implicated in several disease states in the elderly. We examined the effects of sucralfate, a basic aluminum salt of sucrose sulfate, and ranitidine, administered individually and in combination, on plasma and urine aluminum concentrations in the elderly in a prospective, randomized, three‐arm crossover study. Subjects were 20 healthy volunteers over age 65 years, with no clinically significant comorbidities or recent use of aluminum‐containing drugs or histamine (H)2‐antagonists. The three regimens were ranitidine 300 mg at bedtime, sucralfate 1 g 4 times/day, and ranitidine 300 mg at bedtime plus sucralfate 1 g 4 times/day, administered for 4 weeks, with a washout period of at least 1 week between regimens. Plasma and urine aluminum concentrations were measured on days 0, 1, 7, 14, and 28 of each regimen. After 28 days, mean plasma aluminum concentrations were significantly higher in subjects receiving sucralfate alone (8.5 ± 1.8 μg/L) and sucralfate plus ranitidine (5.1 ± 1.3 μg/L) compared with those receiving ranitidine alone (2.4 ± 0.7 μg/L). Urine aluminum concentrations were significantly higher in subjects receiving sucralfate alone (133.2 ± 32.8 μg/g creatinine) and sucralfate plus ranitidine (148.1 ± 51.9 μg/g creatinine) compared with those receiving ranitidine alone (11.0 ± 3.7 μg/g creatinine). There was no significant difference in plasma or urine aluminum concentrations between subjects who received sucralfate alone versus those who received sucralfate plus ranitidine. Sucralfate 4 g/day in elderly subjects produces a significant increase in both plasma and urine aluminum concentrations, compared with ranitidine 300 mg/day. This increase most likely is secondary to gastrointestinal absorption of aluminum in the sucralfate formulation. The clinical relevance of this increase requires further evaluation.
Assessment of the Time Course of Drugs With Inhibitory Effects on Hepatic Metabolic Activity Using Successive Salivary Caffeine Tests
Authors: Soto J. , Alsar M.J. , Sacristan J.A.
Published: October 2023

In clinical practice is very important to know the time course of the inhibitory effects of drugs to avoid side effects when several agents are taken concomitantly. We attempted to validate the effectiveness of successive salivary caffeine tests establishing the time for cimetidine to inhibit hepatic metabolism. The time of cimetidine's inhibitory effect as reported in other studies was chosen as the reference. In this open‐label, prospective longitudinal, 16‐day study, five healthy volunteers were treated with cimetidine 1 g/day for 5 days. After the intake of caffeine 300 mg, salivary caffeine tests were carried out on days −1 (control value), 1, 4, 8, 12, and 16. The mean systemic caffeine clearance was decreased after 24 hours of cimetidine. The drug's maximum inhibitory effect was reached after 5 days of administration, returning to previous values progressively 1–7 days after discontinuing cimetidine. No change occurred in the apparent volume of distribution. The time course of cimetidine's inhibitory effect was similar to that described with other methodologies. Although this was a pilot trial and the results have to be confirmed, it seems that successive salivary caffeine measurements could be a safe, reliable, noninvasive test for exploring the time course of the inhibitory effects of drugs on hepatic metabolism.
Antihypertensive Drug Use in the Long‐Term Care Facility: A Pilot Study and Review of the Literature
Authors: Fish Jeffrey T. , Guay David R.P. , Straka Robert J.
Published: October 2023

The overuse and cost of drugs in long‐term care facilities are of significant concern. To quantify potential overuse of antihypertensive agents, we conducted a retrospective chart review in four long‐term care facilities. We analyzed data in 550 patient records to identify residents receiving drugs for the sole indication of hypertension. Of the 550 records, 49 (9%) residents qualified. Of these, 20 (41%) had all recorded blood pressures less than 140/90 mm Hg for the 6 months before review, and 32 (65%) had all blood pressures less than 160/90 mm Hg. Given this degree of blood pressure control and the reported success of withdrawing antihypertensive drugs from the elderly in whom the disorder is well controlled, a reevaluation of antihypertensive therapy in residents of long‐term care facilities appears to be justified.
Hyperkalemia Associated With High‐Dose Trimethoprim‐Sulfamethoxazole in a Patient With the Acquired Immunodeficiency Syndrome
Authors: Mihm Linda Brockman , Rathbun R. Chris , Resman‐Targoff Beth H.
Published: October 2023

When given in standard dosages to treat bacterial respiratory and urinary tract infections, trimethoprim‐sulfamethoxazole (TMP‐SMX) is not commonly associated with hyperkalemia. However, the emergence of the acquired immunodeficiency syndrome has led to increased numbers of patients with Pneumocystis carinii pneumonia (PCP) who require high‐dose TMP‐SMX therapy. A 25‐year‐old man with human immunodeficiency virus infection developed hyperkalemia while receiving high‐dose TMP‐SMX for PCP. His baseline serum potassium of 3.0 mEq/L, which increased to 4.2 mEq/L after potassium replacement therapy, rose to 6.9 mEq/L after 8 days of TMP‐SMX. No other etiology was found for the hyperkalemia, and the disorder resolved when TMP‐SMX was stopped. It recurred when the patient was rechallenged with high doses of TMP‐SMX during a second treatment course for PCP. This case and a review of previous reports highlight the importance of monitoring serum potassium concentrations in patients receiving high‐dose TMP‐SMX.
Phenytoin Malabsorption After Jejunostomy Tube Delivery
Authors: Rodman Daniel P. , Stevenson T. Lynn , Ray Tracy R.
Published: October 2023

The literature supports interactions between phenytoin and both enteral feeding products and nasogastric feeding tubes; however, no published reports exist regarding the interaction of phenytoin with jejunostomy feedings. A 29‐year‐old woman with cerebral palsy, mental retardation, and a history of seizures was treated with intravenous phenytoin, which yielded detectable therapeutic serum concentrations. After switching to a comparable phenytoin suspension administered by jejunostomy tube, her serum phenytoin concentrations fell to below assay sensitivity concentrations. This drop, nearly 100%, was the greatest that we found reported in the literature. Distal placement of the jejunostomy tube within the small bowel may augment potential phenytoin‐tube‐enteral product interactions. In addition, the possible decrease in gastrointestinal transit time because of anatomic placement may not allow for adequate drug absorption. Decreased phenytoin bioavailability may become more common with increased use of supplemental feeding tubes.
Octreotide‐ or Trimethoprim‐Induced Hyperkalemia?
Authors: Canada Todd
Published: October 2023

The article by Sargent et al1 associating hyperkalemia with octreotide in a 68‐year‐old, 91‐kg trauma victim has little focus on other potential causes of her hyperkalemia. Her medical history was significant for noninsulin‐dependent diabetes mellitus. The authors, however, do not state how long she had this disease and whether she had any evidence of end‐organ damage. The episode of postoperative hypotension, as well as the assumed oliguria (her serum creatinine increased from 1.5 to 2.3 mg/dl) on day 3 of hospitalization, clearly contributed to renal hypoperfusion and potential renal injury. There was no other mention of renal impairment until the laboratory values revealed a serum creatinine of 2.5 mg/dl and a blood urea nitrogen of 91 mg/dl on day 14 of hospitalization. The patient appeared to be volume depleted (blood urea nitrogen:serum creatinine ratio > 20:1, serum sodium 154 mmol/L), and her potassium may have been lower (4.1 mmol/L) secondary to the effects of aldosterone. Interestingly, on day 11, oral (suspension?) trimethoprim‐sulfamethoxazole (TMP‐SMX) 180 mg twice/day (4 mg/kg/day TMP) was started for a urinary tract infection. The next day (day 12), this was changed to the intravenous route at a dose of 320 mg every 8 hours (∼11 mg/kg/day TMP) for suspected pneumonia. The patient's serum potassium was already beginning to rise slowly (4.1 to 4.6 mmol/L) even before the start of octreotide on day 16 despite improving serum creatinine (2.5 to 1.2 mg/dl) and serum sodium (154 to 147 mmol/L).
Bacterial Resistance Mechanisms to β‐Lactam Antibiotics: Assessment of Management Strategies
Authors: Dudley Michael
Published: October 2023

Several mechanisms render antimicrobials inactive; one of these, β‐lactamase hydrolysis of β‐lactam antimicrobials, is a common and serious problem resulting in loss of antimicrobial activity. Resistance in gram‐negative organisms may be caused by chromosomally or plasmid‐mediated β‐lactamases. Chromosomally mediated resistance may result from exposure to inducer compounds (induction) or by selection of stably derepressed mutants. Plasmids are extrachromosomal elements of DNA that can transfer resistance between bacteria. Common plasmid‐encoded β‐lactamases are the TEM‐ and SHV‐type enzymes, which include the newer extended‐spectrum β‐lactamases. Infections caused by resistant bacteria frequently result in longer hospital stays, higher mortality, and increased cost of treatment. When bacteria develop resistance during antimicrobial therapy therapeutic failure ensues in approximately 50% of patients. Clinical studies demonstrate that resistance mediated by β‐lactamases is a critical issue. Strategies for overcoming it include use of β‐lactam‐β‐lactamase inhibitor combinations, development of new antimicrobial compounds, and use of regimens that optimize in vivo exposure to drug.
Quantitative Methods For Quality Improvement
Authors: Jewell Mark A.
Published: October 2023

Measuring clinical and financial outcomes in health care is a science in the early stages of development and implementation. Many tools and techniques are derived from industry models of continuous quality improvement and epidemiology. Epidemiologic (enumerative) and statistical process control (analytic) methods are effective alternatives to traditional quality assurance methods of evaluating patient care that encompass clinical and financial outcomes. Their use has resulted in significant improvement of clinical outcomes and financial performance, and has increased physician involvement in the process. Although cost will be the driving force of health care reform for the next few years, demonstration of high‐quality care by providers through outcomes measurement will differentiate long‐term from short‐term winners in an environment of managed competition. This fact will make the science of outcomes management increasingly more important.
The Effect of Three Different Ranitidine Dosage Regimens on Reducing Gastric Acidity and Volume in Ambulatory Surgical Patients
Authors: O'Connor Thomas A. , Basak Jharna , Parker Susan
Published: October 2023

Study Objective. To evaluate three different preoperative oral dosing regimens of ranitidine in ambulatory patients who had significant risk of aspiration pneumonitis (gastric pH ≤ 2.5 or volume ≥ 25 ml at intubation or extubation).

Design. Double‐blind, placebo‐controlled, randomized trial.

Setting. St. Francis Hospital of Buffalo, New York.

Patients. Two hundred seventy‐one ambulatory patients about to undergo a surgical procedure under general anesthesia, of whom 241 (89%) completed the trial and were considered evaluable.

Interventions. Patients were randomly assigned to receive one of four regimens administered orally before surgery: placebo at bedtime the night before and in the morning on the day of surgery; ranitidine 150 mg at bedtime and in the morning; ranitidine 150 mg at bedtime and placebo in the morning; or ranitidine 300 mg at bedtime and placebo in the morning.

Measurements and Main Results. Patients who received ranitidine 150 mg twice/day ranitidine 150 mg at bedtime, or ranitidine 300 mg at bedtime had a significantly (p<0.05) lower frequency of a gastric pH 2.5 or below at intubation or extubation than those taking placebo twice/day (3%, 45%, and 31%, respectively, vs 86%). In addition, gastric volume at intubation or extubation was 25 ml or above in significantly fewer patients receiving ranitidine 150 mg at bedtime than placebo (37% vs 13%, p<0.05). Overall, the number of patients with risk factors for aspiration pneumonitis was significantly lower with ranitidine 150 mg twice/day (20%), ranitidine 150 mg at bedtime (48%), and ranitidine 300 mg at bedtime (35%) than placebo (86%) (p<0.001), and significantly lower with ranitidine 150 mg twice/day than ranitidine 150 mg at bedtime (p<0.05).

Conclusions. Ranitidine 150 mg twice/day preoperatively reduced to the greatest degree the percentage of patients who developed significant risk factors for aspiration pneumonitis after surgery under general anesthesia.
Accuracy and Reliability of Dosing Equations to Individualize Theophylline Treatment of Apnea of Prematurity
Authors: Bhatt‐Mehta Varsha , Johnson Gary E. , Donn Steven M. , Spadoni Virginia , Schork M. Anthony
Published: October 2023

Apnea of prematurity is associated with high morbidity and mortality. Treatment generally includes supplemental oxygen and theophylline or caffeine. The half‐life of theophylline is prolonged in newborns because of their immature cytochrome P‐450 system, and there is considerable variation in the drug's metabolism in infants. We compared the accuracy, precision, and reliability of two equations that use postnatal age (PNA) to determine a maintenance dosage of theophylline with a standard maintenance dosage (SMD) that produced a steady‐state serum theophylline concentration (STC) of 8 μg/ml for apnea of prematurity in 46 infants less than 34 weeks' gestational age (GA) and less than 36 weeks' postconceptional age (PCA). The two equations were mg/kg/day = [(0.2 × PNA in wks) + 5], and mg/kg/day = [(0.3 × PNA in wks) + 8]. Their reliability to predict the SMD was determined by correlation analysis. The precision and accuracy with which they predicted SMD were determined and analyzed by χ2. The SMD did not correlate with the maintenance dosages calculated by equations 1 and 2 (r=0.296 and 0.296, p>0.05 in both cases). Multiple linear regression of SMD versus GA, PNA, and PCA was not significant (r=0.33, p=0.32). After stratifying data based on GA and performing correlation analysis of SMD versus PNA, a weak but significant correlation (r=0.42, p=0.0517) was found for infants with GA between 31 and 34 weeks. Poor correlation was found between SMD versus PNA for infants 27–30 weeks' GA. Two new equations of the best fit line were generated using the same data. Currently available equations for determining maintenance dosages of theophylline in infants and children are not reliable for premature newborns, in whom two new equations based on GA and PNA have been developed. The equations will be evaluated for their utility, and employed to accrue data to determine if better ones can be developed.
Schizophrenia: Its Etiology and Impact
Authors: Miller Del D.
Published: October 2023

Schizophrenia is a devastating illness that can impair all aspects of a patient's life. Although positive psychotic symptoms such as hallucinations and delusions are often emphasized, the negative symptoms of the disease prevent patients from functioning in society and limit their ability to hold a job, attend school, or form friendships. Since schizophrenia is most likely to develop between ages 15 and 25 years, its effects are felt throughout a person's life. Much research has been conducted on the etiology of the disorder, but no single cause has been identified. Most likely, it is the result of a combination of genetic, environmental, and neuropathologic factors. The costs of schizophrenia are high. These patients occupy about 25% of hospital beds. They are paid approximately 10% of Social Security benefit days, as they are often too ill to work. Given the high costs of hospital care, any pharmacologic or psychosocial therapy that can prevent hospitalization will play an important role in the treatment of these patients.
Novel versus Conventional Antipsychotic Drugs
Authors: Love Raymond C.
Published: October 2023

Novel antipsychotic agents differ from conventional ones in several key characteristics, including effectiveness, adverse reactions, and receptor‐binding profile. Most of the newer agents have an affinity for the serotonin 5HT2 receptor that is at least f 0 times greater than that for the dopamine D2 receptor. This increased affinity for the serotonin receptor may be responsible for another distinguishing characteristic of novel antipsychotic agents—decreased frequency of extrapyramidal side effects. These side effects, which include pseudoparkinsonism, acute dystonias, and akathisia, frequently are the reason for noncompliance with conventional drug therapy. The newer drugs are often effective in patients resistant to treatment with conventional agents. They also appear to reduce the negative symptoms of schizophrenia in many patients.
New Approaches to Adjuvant Chemotherapy for Breast Cancer
Authors: Hudis Clifford
Published: October 2023

Adjuvant chemotherapy improves the disease‐free and overall survival of patients with resectable, early‐stage breast cancer. However, the effect is modest, and we need means of increasing its impact. Retrospective and prospective studies on the effects of increased drug dosage have demonstrated that within some dose ranges, increasing the dose intensity (total drug dose divided by total treatment time) improves the outcome of treatment. Dose escalation to higher levels, sufficient to require growth factor and autologous stem cell support, is the subject of ongoing randomized study. Because there are both theoretical and practical limits on the potential effectiveness of single‐cycle, high‐dose chemotherapy, researchers are developing alternative means of increasing the effect of chemotherapy. One theoretically advantageous approach, predicted to be superior by kinetic models, is “dose‐dense” chemotherapy administration. This approach consists of multiple cycles of escalated‐dose chemotherapy administered at very short intervals. When administering presumed non‐cross‐resistant regimens or agents with overlapping toxicity, clinicians can increase dose density by using the sequential treatment plan. Furthermore, this plan can also facilitate the addition of new active drugs.
Peripheral Blood Progenitor Cell Transplantation for Breast Cancer: Pharmacoeconomic Considerations
Authors: Gilbert Colleen J.
Published: October 2023

The recent observation that mobilized peripheral blood progenitor cells (PBPCs) can be used as a source of hematopoietic support has had a major effect on the cost and morbidity associated with bone marrow transplantation in patients with breast cancer. The pharmacoeconomic impact of this new technology is especially evident when secondary costs are analyzed. We see a reduction in hospital stay, decreased use of resources such as platelet transfusions and antibiotics, and long‐term quality life‐years gained for those patients benefiting from this therapy. Experienced transplant centers have found that the direct cost of high‐dose chemotherapy using filgrastim and PBPC support is reduced as much as 50% to the patient or their insurance company. Pharmacists will play a key role in optimizing the benefits of PBPC transplantation, particularly because this therapy is moving to the outpatient arena. This article will review the pharmacoeconomic impact of PBPC transplantation primarily in terms of secondary cost measures and quality of life and discuss the limited direct cost data available and the impact of this therapy on pharmacy practice.
Pharmacokinetics and Pharmacodynamics of a Parenteral Testosterone Microsphere Formulation in the Male Rat
Authors: PEACOCK N. R. , SWERDLOFF R. S. , BERMAN N. , GILLEY R. M. , TICE T. R. , BHASIN S.
Published: October 2023

ABSTRACT: This study examined the pharmacokinetics (the time course and pattern of testosterone release) and pharmacodynamics (effects on accessory sex organ weights, and serum LH and FSH levels) of a biodegradable testosterone microsphere formulation in the male rat. Two hundred seventy‐five 55‐day‐old, sexually mature male rats underwent surgical orchiectomy or sham surgery and were divided into five groups as follows, to receive placebo or testosterone microsphere systems designed to release 25, 75, or 225 μg/day testosterone: group I: intact age‐matched controls, sham operated, placebo microspheres; group II: surgically orchiectomized, placebo microspheres; group III: surgically orchiectomized, 25 μg/day testosterone microspheres; group IV: surgically orchiectomized, 75 μg/day testosterone microspheres; and group V: surgically orchiectomized, 225 μg/day testosterone microspheres.

Serum testosterone levels were fairly uniform from day 2 to 85 without any significant trend. After day 100, serum testosterone levels gradually fell into the castrate range by day 196. There was a dose‐dependent increase in serum testosterone levels in groups III, IV, and V over those seen in group II (castrated rats, placebo treated). Prostate and seminal vesicle weights were significantly lower in castrated animals treated with placebo or the 25‐μg/day testosterone microsphere system (group III). Mean prostate and seminal vesicle weights in groups IV and V were not significantly different from those in intact controls (group I) in the first 85 days. After day 85–100, seminal vesicle and prostate weights declined gradually in groups III, IV, and V, approaching castrate range by day 196. Serum LH and FSH levels were higher in castrated rats treated with placebo (group II) or 25 μg/day testosterone (group III). The 75‐μg dose maintained serum LH and FSH levels in the normal male range, and the highest dose (225 μg/d) lowered serum LH levels below those seen in intact rats. After day 100, serum testosterone levels in groups III, IV, and V gradually fell into the castrate range. We conclude that this biodegradable testosterone microsphere formulation provides uniform and dose‐dependent release of testosterone for 10–14 weeks and is worthy of further evaluation as a method of testosterone replacement.
Sperm Function and Choice of Preparation Media: Comparison of Percoll and Accudenz Discontinuous Density Gradients
Authors: SBRACIA MARCO , SAYME NABIL , GRASSO JOHN , VIGUE LYNNE , HUSZAR GABOR
Published: October 2023

ABSTRACT: We compared the sperm populations prepared by Accudenz (35–65%) and Percoll (40–80%) density gradients in 21 normospermic specimens (concentration, 53.6 ± 3.8 × 106 sperm/ml; motility, 44.5 ± 3.5%). Accudenz facilitated a higher recovery of sperm and motile sperm (68.4 ± 6.6% vs. 49.3 ± 4.9%, P < 0.001, and 87.8 ± 4.1% vs. 77.8 ± 3.7%, P < 0.01, respectively). Sperm motility was lower in the Accudenz compared to the Percoll pellets; thus the values of total motile sperm recovered were not different (17.1 ± 2.4 vs. 15.1 ± 2.2 × 106 sperm/ml). The long‐term retention of sperm motility was substantially improved in Accudenz (at 24 hours, 34.9 ± 2.8% vs. 26.3 ± 1.5%; 60% vs. 40% of the initial motility, P < 0.001), and the Accudenz vs. Percoll samples also exhibited a higher retention of total motile sperm (at 24 hours, 9.8 ± 1.2 vs. 6.1 ± 0.5 × 106 motile sperm/ml, P < 0.05). The sperm motility index, a multiple of velocity and motility in the sample that reflects the efficiency of the sperm population in sperm‐oocyte interaction, was 75% higher in the Accudenz samples at 24 hours (3.6 ± 0.4 vs. 2.1 ± 0.2, μm/second, P < 0.01). Sperm cellular maturity by the creatine phosphokinase (CK) activity and CK‐M to CK‐B isoform ratio parameters (in the original samples 0.14 ± 0.02 IU CK/100 × 106 sperm and 57.9 ± 3.7%, respectively) were improved in both the Accudenz and Percoll pellets (P < 0.001), with no difference between the two sperm fractions. Sperm activation status monitored by chlortetracycline fluorescence indicated that after 4 hours of incubation the incidence of fully acrosome‐reacted spermatozoa in the Accudenz versus Percoll pellets was 6.2 ± 0.3% versus 13.1 ± 1.0% (P < 0.001), a 100% increase in Percoll. We can conclude that Accudenz yields a higher concentration of motile spermatozoa, with improved retention of motility, velocity, and acrosomal integrity and without an increase of sperm with diminished cellular maturity. Thus, in sperm preparation for intrauterine insemination, in which the timing of ovulation and insemination frequently do not correspond, Accudenz‐prepared sperm, with a better retention of motility/velocity and acrosomal integrity and with a consequential higher resistance to activation by the female reproductive tract, are expected to be more effective.
Methodological Issues in the Analysis of Human Sperm Concentration Data
Authors: BERMAN NANCY G. , WANG CHRISTINA , PAULSEN C. ALVIN
Published: October 2023

ABSTRACT: We examined two methodological issues in the analysis of sperm concentration data using a large database of sperm concentrations in healthy men that were collected at the University of Washington. We showed that the raw data were skewed and that log transformation should be used to assure that the data meet the assumptions underlying most statistical estimation and testing procedures. We also addressed the issue of the great variability in sperm concentrations within a single individual and the necessity and utility of multiple sampling to reduce variance. We conclude that log‐transformed data should be used for statistical analysis of sperm concentration and recommend that such analyses be based on the geometric mean of several samples from each subject to reduce variability, increase accuracy of estimation, and improve statistical power. This is particularly important when the objective is to detect small but important differences or subtle effects.
Increased Proliferation of Leydig Cells Induced by Neonatal Hypothyroidism in the Rat
Authors: HARDY MATTHEW P. , SHARMA RADHEY S. , ARAMBEPOLA NIROMI K. , SOTTAS CHANTAL M. , RUSSELL LONNIE D. , BUNICK DAVID , HESS REX A. , COOKE PAUL S.
Published: October 2023

ABSTRACT: Treatment of male rat pups with the reversible goitrogen 6‐n‐propyl‐2‐thiouracil (PTU), administered by adding 0.1% PTU to the mother's drinking water from birth through weaning, increases adult testis size, number of Sertoli cells, and daily sperm production. Adult Leydig cell numbers are also increased by 70%, despite permanent suppression of serum luteinizing hormone (LH). The present study was designed to test whether this effect results from an increase in proliferation of Leydig cells or the mesenchymal precursors. The labeling indices (LI) of six interstitial cell types were measured by tritiated thymidine autoradiography. With the exception of Leydig cells, LI declined after birth for all interstitial cell types in both control and PTU‐treated rats, but mesenchymal cell proliferation was not significantly different in control and treated rats. In contrast, the LI of Leydig cells from PTU‐treated rats rose by day 10, remained elevated through day 45 (highest on day 35 at 3.6‐fold higher than control, P < 0.05), and declined to control values by day 50. The LI of Leydig cells in control rats was unchanged during the experiment.

Proliferating Leydig cells were immature, as shown by their cytoplasmic lipid droplets. Adult Leydig cells, which lack lipid droplets, did not proliferate. Mesenchymal and immature Leydig cells contained thyroid hormone receptor mRNA; levels in adult Leydig cells were reduced but detectable. In conclusion, proliferation of Leydig cells, rather than increased proliferation of their mesenchymal precursors, is the principal mechanism responsible for the increase in Leydig cell number after neonatal hypothyroidism. Increased Leydig cell proliferation could result from direct effects of hypothyroidism on these cells. Alternatively, the increased Sertoli cell population that results from PTU treatment could also stimulate increased Leydig cell proliferation, or both of these mechanisms could contribute to the Leydig cell increase.
Seminal Fluid Findings in Men With Nonbacterial Prostatitis and Prostatodynia
Authors: KRIEGER JOHN N. , BERGER RICHARD E. , ROSS SUSAN O. , ROTHMAN IVAN , MULLER CHARLES H.
Published: October 2023

ABSTRACT: There is considerable confusion about the effects of prostatitis syndromes on male reproductive physiology. Therefore, we correlated findings on seminal fluid and expressed prostatic secretions from 100 men attending a special prostatitis clinic. These men had symptoms of prostatitis but no evidence of urethritis, acute or chronic bacterial prostatitis, or significant urological abnormalities. All subjects were evaluated following a standardized protocol, including lower urinary tract localization studies, expressed prostatic secretion analyses, and seminal fluid analyses with Bryan‐Leishman staining. Seminal fluid findings were compared in men with inflammation (≥106 leukocytes/ml) in their expressed prostatic secretions, i.e., nonbacterial prostatitis, and men without inflammation in prostatic secretions, i.e., prostatodynia. Of 23 men with inflammation (≥106 leukocytes/ml) in their seminal fluid, 6 (26%) had nonbacterial prostatitis (mean leukocyte concentration 8.6 ± 9.4 × l06/ml of semen) and 17(74%) had prostatodynia (mean leukocyte concentration 6.2 ± 7.0 × 106/ml, not significant) Of 77 men who did not have seminal inflammation, 15 (19%) had nonbacterial prostatitis (mean leukocyte concentration 0.1 ± 0.2 × 106/ml) and 62(81%) had prostatodynia (mean leukocyte concentration 0.1 ± 0.2 × l06/ml, not significant). Men with nonbacterial prostatitis had lower values for several parameters associated with sperm motility, especially the proportion of motile sperm (45% compared with 60% for men with prostatodynia, P = 0.08) and sperm subjective speed score (median 3 compared to 4 for men with prostatodynia, P = 0.03). In summary, a minority of men had seminal inflammation, even among men with nonbacterial prostatitis. There was poor correlation between inflammation in the prostatic secretions and in the semen. Nonbacterial prostatitis, but not seminal inflammation, was associated with reduced sperm motility. Our findings highlight technical issues and the importance of investigating different sites and samples, including the urethra, expressed prostatic secretions, and seminal fluid.
Fabrication of alginate‐based hydrogel microparticle via ruthenium‐catalyzed photocrosslinking
Authors: Noori Fariba , Jafarbeigloo Hamid Reza Ghaderi , Jirehnezhadyan Mozhgan , Mohajer Maryam , Khanmohammadi Mehdi , Goodarzi Arash
Published: October 2023

In this study, we developed an alginate‐based microparticle production process via sodium ruthenium(II) tris‐bipyridyl dication (Ru)/ammonium persulfate (SPS)‐mediated visible light crosslinking system using a microfluidic device. Microparticles were prepared by crosslinking phenolic‐substituted alginate (AlgPh) and incorporated gelatin (GelPh) in an aqueous solution containing SPS, which flowed into an ambient immiscible liquid paraffin‐containing Ru using coaxial double orifice microfluidic device. The hydrogel microparticles appeared with the desired geometries and dimensions under optimal conditions. The concentration of AlgPh and light intensity were the most critical parameters for harvesting spherical microparticles with homogeneous size distribution. The physical properties of the prepared AlgPh microparticles were characterized and compared with Alg‐Ca microparticles. Cell viability and proliferation preserved on AlgPh/GelPh hydrogel surfaces. Also, encapsulated cells in microparticles were also viable and proliferated well over 13 days after encapsulation. In brief, the results proved the feasibility of fabricating AlgPh vehicles via Ru/SPS‐mediated system and visible light irradiation as a simple and efficient three‐dimensional platform, which are applicable for various tissue engineering and cell delivery purposes.
Associations of Quantitative and Qualitative Muscle Parameters With Second Hip Fracture Risk in Older Women: A Prospective Cohort Study
Authors: Zhang Wenshuang , Ge Yufeng , Liu Yandong , Yuan Yi , Geng Jian , Zhou Fengyun , Huang Pengju , Shi Jia , Ma Kangkang , Cheng Zitong , Blake Glen M. , Yang Minghui , Wu Xinbao , Cheng Xiaoguang , Wang Ling
Published: October 2023

Older women with a first hip fracture exhibit heightened susceptibility and incidence of second fracture and potentially severe consequences. This prospective study was to compare the predictive power of qualitative and quantitative muscle parameters for a second hip fracture in older women with a first hip fracture. A total of 206 subjects were recruited from the longitudinal Chinese Second Hip Fracture Evaluation study. Hip computed tomography (CT) scans were obtained immediately after the first fracture. Muscle fat infiltration was assessed according to the Goutallier classification qualitatively. Quantitative parameters included cross‐sectional area and density of gluteus maximus (G.MaxM) and gluteus medius and minimus (G.Med/MinM) muscles. CT X‐ray absorptiometry was used to measure the areal bone mineral density (aBMD) of the contralateral femur. Cox proportional hazards models were used to compute hazard ratios (HR) of second hip fracture risk. The mean age of subjects was 74.9 (±9.5) years at baseline. After 4.5 years, 35 had a second hip fracture, 153 without a second hip fracture, and 18 died. Except for the combined G.MinM Goutallier grade 3 and 4 groups before adjustment for covariates (HR = 5.83; 95% confidence interval [CI] 1.49–22.83), there were no significant HRs for qualitative classification to predict a second hip fracture. Among quantitative metrics, after adjustment for covariates, G.Med/MinM density was significant in the original (HR = 1.44; CI 1.02–2.04) and competing risk analyses (HR = 1.46; CI 1.02–2.07). After additional adjustment for femoral neck (FN) aBMD, G.Med/MinM density remained borderline significant for predicting a second hip fracture in competing risk analysis (HR = 1.43; CI 0.99–2.06; p = 0.057). Our study revealed that Goutallier classification was less effective than quantitative muscle metrics for predicting hip second fracture in this elderly female cohort. After adjustment for FN aBMD, G.Med/MinM density is a borderline independent predictor of second hip fracture risk. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.