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Charging for hospital pharmaceutical services: product cost, per diem fees and fees for special clinical services.

A method of charging for pharmaceutical services is described which includes the cost of drug products, dispensing fees for intravenous drug admixtures, per diem fees for basic dispensing and clinical services (according to patient type), and fees for special clinical services. The basic per diem charge covers drug purchasing and inventory control, department management, drug information services, dose preparation, drug order interpretation, drug therapy monitoring, and the availability of pharmacists to answer the questions of nurses and physicians. The clinical services for which special fees are charged are: hemogram drug report, drug liver function report, aminoglycoside dosing guidelines, heparin i.v. infusion, oral anticoagulation, patient drug history, operant conditioning, parenteral nutrition guidelines, and pharmacokinetic drug level interpretations and consultations. The reasons for changing to the system, the services provided and experiences with the system are discussed. Implementation of the system is discussed in relation to the calculation of fees; comparisons with alternate charging methods; approval of special clinical service charges; computer billing; information about pharmacy charges for patients; and third-party payers.

California

Some economic and technical factors affecting use of phosphate raw materials.

In comparison with phosphate resources most of the other industrial minerals essential to man have much higher unit values. Furthermore, they generally have more narrowly defined geochemical origins, concentration requirements, and end-use markets. Consequently, an economic assessment of their mined production cost in relation to market value is more easily and reliably defined. Thus, the mere knowledge of existing or newly discovered ore bodies provides economic incentives for exploitation plans--even in the most remote geographical location (as is well illustrated by iron, copper, tin, lead, and similar mineral commodities). Unfortunately, this is not the case for phosphate resources. Much of the known vast reserves of more than 1 X 10(11) tons, which are favourably dispersed among the worldwide markets, remains uneconomical to recover, despite the growing need for phosphate in world food production. A complex set of interrelated technical and economic factors decide the economic potential of any particular phosphate reserve. Although technical similarities may exist among deposits, economic analogies are rare. The economic evaluation of the mineability of the ore and the mill preparation of the concentrates must also take into account the geological setting and character of the ore deposit as well as the eventual end-use markets and their locations.

Aluminum

Molecular Mobility of N-Acetylgalactosamine-Modified Cyclodextrins on a Polyrotaxane for Highly Efficient Liver Targeting of Antibody Chimeras and Genome-Editing Ribonucleoproteins.

Triantennary N-acetylgalactosamine (triGalNAc), which interacts strongly with the trimeric structure of asialoglycoprotein receptors (ASGPRs), is a validated platform for liver targeting. However, the intricate design and synthesis of its linkers impose high production costs and significant technical challenges. In this study, we report an alternative strategy for targeting ASGPR using monovalent GalNAc (monoGalNAc) conjugated to the cyclic molecules of polyrotaxane, which can rotate and translocate along the axial polymer chain. The intracellular uptake efficacy of monoGalNAc-modified polyrotaxane is comparable to that of triGalNAc-modified polyrotaxane and significantly higher than that of triGalNAc- or monoGalNAc-modified immobile control polymers. These results suggest that the inherent mobility of polyrotaxanes allows monoGalNAc moieties to cluster in a trivalent-like manner, thereby enhancing multivalent interactions with multiple ASGPR oligomers. The successful application of monoGalNAc-modified polyrotaxane to lysosome-targeting antibody chimeras and genome-editing nanoparticles demonstrates that this facile technology is a highly promising alternative to conventional triGalNAc.

Rotaxanes

Heterologous expression and optimization of the antimicrobial peptide acidocin 4356 in Komagataella phaffii to target Pseudomonas aeruginosa.

Multidrug-resistant (MDR) pathogens, particularly Pseudomonas aeruginosa, pose a serious global health threat due to their increasing prevalence and limited therapeutic options. Antimicrobial peptides (AMPs) offer promising alternatives to traditional antibiotics, yet their large-scale application remains constrained by high production costs and technical challenges. This research sought to develop a yeast-based system for the cost-efficient synthesis of acidocin 4356 (ACD), an antimicrobial peptide proven effective against P. aeruginosa. A codon-optimized ACD gene was cloned into the pPICZα-A expression vector and integrated into the Komagataella phaffii (formerly Pichia pastoris) GS115 genome. Colony PCR confirmed successful integration, and specific transformants demonstrated expression of the 6 × His-ECS-rACD fusion protein, as verified by SDS-PAGE and dot blot analysis. After Ni-NTA chromatography and enterokinase digestion, rACD was found at ~ 20 kDa instead of 8.3 kDa, suggesting oligomerization or post-translational modifications. Response surface methodology determined the optimal temperature, pH, and methanol concentration for peptide synthesis. Under optimal circumstances (21 °C, pH 6.24, and 1.089% methanol), rACD synthesis increased by 34.12% over baseline conditions (30 °C, pH 6, 1% methanol). AlphaFold structural modeling identified three α-helices in high-confidence regions, implicated in bacterial membrane disruption. Antimicrobial assays demonstrated potent rACD activity against P. aeruginosa, yielding a 58.29% reduction in growth at 150 µg/mL and MIC50 and MIC90 values of 143.04 and 320.64 µg/mL, respectively. These findings underscore K. phaffii as a robust platform for AMP production and highlight rACD's therapeutic potential as an effective agent against MDR P. aeruginosa, warranting further investigation into its clinical and industrial applications. KEY POINTS: • Developing a novel K. phaffii strain for heterologous expression supports efficient rACD peptide production. • Optimized conditions boosted expression yield by 34.12% above the reference fermentation settings. • Recombinant acidocin suppressed Pseudomonas aeruginosa growth by 58%, indicating anti-MDR activity.

Pseudomonas aeruginosa

Recombinant bovine chymosin expression in microalgae Chlamydomonas reinhardtii chloroplast: A step towards algal biomanufacturing of dairy enzymes.

Chymosin is the major proteolytic enzyme for cheese manufacture, where it plays an important role in the co-precipitation of milk casein. Traditional extraction of chymosin from the abomasum of young ruminants is associated with high limitations, including low yield, high production cost, and ethical issues of animal slaughter. In this study, we report on a recombinant strategy towards the production of bioactive Bos taurus chymosin in the chloroplasts of the microalga Chlamydomonas reinhardtii. The cym gene encoding preprocymosin was inserted into the chloroplast genome by the glass bead-mediated DNA transformation procedure. Successful integration and expression of the transgene were confirmed by spot test analysis, polymerase chain reaction (PCR), western blot, and enzyme-linked immunosorbent assay (ELISA). The functional activities of the recombinant enzyme were checked by the standard milk clotting assay. The engineered microalgal strains produced chymosin with an average concentration of 90 mg/kg fresh weight, i.e., 1.6% of the total soluble protein. These results show that chloroplast-engineered C. reinhardtii is a promising, sustainable, and animal-free platform for the efficient production of the industrially relevant chymosin.

Animals

Self-healing materials for food packaging: Design principles, activation mechanisms and implications for food safety.

Self-healing materials (SHMs), originally developed to restore mechanical integrity, have recently attracted growing interest in food packaging. By autonomously repairing physical damage, SHMs help preserve packaging integrity, barrier performance, food safety, and shelf-life during storage and transportation. This review summarizes recent advances in the design principles, activation mechanisms, material systems and food packaging applications of SHMs. Key healing strategies, including microencapsulation, dynamic covalent bond exchange, reversible non-covalent interactions and responsiveness to external stimuli such as temperature, pH, and humidity, are discussed. Representative material systems, including biopolymer-based films, hydrogels, nanocomposites, and stimuli-responsive polymers are evaluated with respect to their relevance to packaging animal-derived foods, fruits, and vegetables. Performance evaluation methods, sustainability implications, and food-contact safety concerns are addressed. Despite promising healing efficiency and mechanical resilience, challenges remain regarding production cost, food-grade safety, migration risks, trigger compatibility and stability under fluctuating environmental conditions. Future research should focus on scalable manufacturing, standardized evaluation protocols, repeated damage-healing safety assessment, regulatory compliance, and integration with intelligent packaging technologies.

Food Packaging

Structural characterization and predicted biosynthetic pathway of the polysaccharide component of bioflocculant from starch-degrading Bacillus subtilis ZHX3.

Polysaccharides-based bioflocculant is a promising eco-friendly alternative to conventional flocculants, yet their application is limited by high production cost. Understanding the biosynthetic pathway is essential for targeted strain improvement. In this study, we characterized polysaccharides structure of bioflocculant MBF-ZHX3 from Bacillus subtilis ZHX3 and predicted its biosynthetic pathway via genomic analysis combined with quantitative real-time PCR (qPCR). Two purified polysaccharide fractions, PS1-1 (5982 Da) and PS2-1 (17,577 Da), were obtained. Both were mainly composed of glucose, with a backbone of →4)-α-D-Glcp-(1 → and α-D-Glcp-(1 → branches attached at O-6. Whole-genome sequencing revealed a circular chromosome of 4,122,369 bp and two plasmids. Functional annotation showed high carbohydrate metabolism activity, with 284 genes (9.52%) and 264 genes (11.28%) assigned to carbohydrate metabolism in the COG and KEGG database, respectively. A complete eps gene cluster consisting of 15 open reading frames was identified. qPCR showed that key genes involved in substrate uptake (ptsG, malP, mdxEFG-msmX) and nucleotide sugar synthesis (pgcA, gtaB) were significantly upregulated. The priming glycosyltransferase (GT) epsL and the primary GT epsF were upregulated, along with the flippase epsK, polymerase epsG, and chain-length regulators epsA and epsB. Based on these findings, we propose a putative biosynthetic pathway for the polysaccharide component of MBF-ZHX3, and identify epsL, epsF, and epsG as prioritized targets for future genetic engineering. This work provides an integrated structural-genomic-transcriptomic framework that can guide rational strain improvement to enhance bioflocculant production.

Polysaccharides structure

Modified Plasmids and Inverted Terminal Repeats Enhance Adeno-Associated Virus Production and Performance.

Recombinant adeno-associated virus (rAAV) is a preferred vector in gene therapy, although high production costs inhibit widespread adoption. The most common approach for rAAV production involves transfection of HEK293 cells with three plasmids: pTransgene, pRep/Cap and pHelper. Producing sufficient amounts of these plasmids accounts for up to 40% of total batch costs. Initially, this work aimed to increase plasmid yields by replacing the backbones. While this approach increased pHelper yields, pRep/Cap and pTransgene yields were unaffected. A possible reason was identified: pTransgene contains inverted terminal repeat (ITR) sequences that are essential for rAAV production. ITRs have strong secondary structures (including hairpin loops termed B and C arms) that likely interfere with plasmid production. Therefore, targeted deletions were performed within the ITRs. Partial deletions in both the B and C arms of the ITR were most beneficial, as both plasmid yield and transgene expression increased. Importantly, partial deletions did not reduce rAAV yield, as had been previously observed when the B and C arms were fully deleted. In summary, we report a 140% increase in pHelper plasmid production, while the most successful ITR variant increased pTransgene plasmid yields by 57% and transgene expression by 28%, without reducing rAAV yields or transduction efficiency.

Humans

A new parallel plate dialyser. II. Description of design and in vitro performance.

Using a high efficiency membrane support pattern, described in the previous paper, a prototype of a new parallel plate dialyser has been developed. The new dialyser is designed in such a way that the number of components is reduced to one item per blood layer and the membrane is folded as a continuum. This permits a semiautomatic assembly of the unit, which reduces production costs. Furthermore this technique facilitates aseptic handling of the item. The in vitro performance has been tested and it compares favorably with commercially available disposable parallel plate dialysers.

Biomedical Engineering

Educating patients with Osteoarthritis.

An education program was developed for geriatric patients with osteoarthritis utilizing adult learner methods. The format used was slide/tape with accompanying booklets. Sixty-seven patients were tested before, immediately after, and three weeks after viewing the programs. A change in knowledge was noted for all objectives and was statistically significant (P .05) in five of six objectives. Although initial production costs are substantial, duplication costs are minimal. These results suggest that geriatric patients with osteoarthritis are able to learn and the method used is a cost-effective one.

Cost-Benefit Analysis

Helping staff to manage conflict well.

A hospital that trains its staff to deal assertively with conflict can become more effective in terms of productivity, cost effectiveness, and patient satisfaction. A training model for handling conflict in the work setting is described.

Aggression

Developing drug-use profiles from drug-charge records.

The potential for developing a drug-use profile from drug-charge records was studied at an 830-bed community hospital. Patient drug charges were reviewed retrospectively for one year (1975) to identify: (1) which key drugs accounted for a high percentage of cost and usage; (2) where key drugs were used within the hospital; (3) how they were used; and (4) who were the chief prescribers. Of the drugs used, 8% accounted for 80% of total drug product costs. Seven drug groups (10% of the total drug groups) appeared in the top 10 of both drug cost and quantity categories. Six individual drugs also appeared in the top 10 of both categories. According to cost, cephalosporin antibiotics were ranked first among drug groups but were sixth according to quantity. Analgesics-antipyretics were ranked first among drug groups by quantity and second by cost. Cephalothin was ranked first among individual drugs by cost and was not in the top 10 in quantity. Diazepam was ranked first among individual drugs by quantity and third by cost. Patients' drug-charge records can be used effectively to generate drug-use profiles for ongoing drug use review, quality assurance and cost containment programs.

California

The need for integrated control programs for zoonoses affecting livestock.

Prior to recognition of etiologic agents of zoonoses (infections transmitted between animals and man), physicians encountered these illnesses in man and veterinarians observed them in animals. As the agents were identified, interspecies relationships (and spread) became evident and control programs evolved without consideration of cost-effectiveness. Today, the public demands efficient use of financial resources. Human health as well as economic losses are concerns of animal health agencies. Zoonoses affecting livestock, though not major priorities among public health agencies, cannot be ignored. It seems economical, therefore, to combine the efforts of these agencies in zoonoses control. This would benefit human health by reducing the animal reservoirs and the livestock industry will benefit by lowered production costs.

Animals

[Combined vaccines in veterinary medicine in the developing countries].

It is in the interest of developing countries to have combined vaccines in veterinary medicine, not so much because they reduce production costs, but rather because they increase convenience and efficacy concerning the logistics of prophylactic projects in the field, thus lowering the cost of these projects. Their drawbacks are basically due to the biological compatibility of immunogens (possible immunosuppression by some viruses) and to the interaction of the various components when mixed, or when lyophilization is carried out. Some examples of such associations of vaccines are: (1) cattle plague + pleuropneumonia and possibly anthrax, (2) anthrax + blackleg, (3) sheeppox + anthrax, (4) pleuropneumonia + blackleg, (5) Newcastle disease + fowlpox + fowl typhoid, (6) fowl typhoid + chicken pasteurellosis. Practical results have been most positive and include the eradication of cattle plague - a major scourge of almost all of the African continent - and control over peripneumonia as a first step towards its eradication.

Africa

Karyology: vaccine manufacturers' views.

Chromosomal analyses and life span studies of WI-38 cell cultures used for vaccine production at the Connaught Laboratories Ltd will be described. Twenty cultures derived from the same seed lot and 25 cultures derived from different starter cultures were analyzed. Karyology tests at population doublings 31 and higher were within acceptable limits. The WI-38 cells reached a finite lifespan of approximately 65 population doublings. Normal growth characteristics were observed within 2/3 of the finite lifespan, i.e. until population doubling 40. The finite lifespan of MRC-5 was found to be 75 population doublings, with normal growth pattern until passage 50. The karyology test results, cell yields and the finite lifespans indicated that these cells could be used as substrates for vaccine production at higher passage levels than previously suggested. Using serially subcultivated cells at higher passage levels would make possible an increase in the volume of vaccine from existing cell seed and would also result in significant reduction in production costs.

Cell Survival

C.A.B.: a practical contact lens option?

The rigid contact lens continues to offer many prescription features which are difficult to match in the flexible lens realm, e.g.,: readily measured parameters, predictable optics, low production cost and minimum patient care requirements for reasonable hygienic safety. But poor tear pump efficiency remains a challenge in many conventional (i.e., PMMA) cases, even today. Oxygen permeable rigid materials represent the obvious solution to this problem, but how adequately do they perform? Two such materials are examined in this report in relation to the oxygen needs of the cornea.

Cellulose