Parallel importation of patented products, “first sale doctrine,” is an effective and efficient way of handling the importation of patent-protected goods. The national exhaustion idea is being used in Pakistan regarding patent exhaustion. Market competition and lower pricing phenomena are affected by this strategy. Case studies from the European Union (EU), the United States (US) and China are used to show how businesses can protect consumers’ rights by parallel imports. The US and China follow international exhaustion whereas the EU follows the regional exhaustion principle, which is comparable with Pakistan concerning the Shanghai Cooperation Organization (SCO). By finding lower-priced products, promoting international economic integration and regional collaboration with SCO, Pakistan can avail better investment opportunities. Case studies show result-oriented efforts regarding the implementation of the international parallel exhaustion strategy. Study recommends raising awareness and enhancing legal clarity, IP protection, and stakeholder input to ensure compliance with an international exhaustion system.

Purpose: In this qualitative descriptive study, we aimed to explore the experiences of nurses providing end-of-life (EOL) care in an emergency department (ED) setting and identify the associated challenges and implications for clinical practice. Methods: Twelve nurses with over 1 year of EOL care experience in the ED were interviewed. The collected data were analyzed using thematic analysis, as outlined by Braun and Clarke. Results: Five main themes with corresponding subthemes were identified: (1) Inadequate Environment for EOL Care, including physical environment barriers for a dignified death and emotional restraint in a chaotic setting; (2) Impact of Life-Sustaining Treatment Decision Complexity, encompassing complicated dynamics of family decision-making and compromised care quality in the decision-making process; (3) Managing Care Relationships in Physician-Limited Settings, manifested as navigating limited physician communication and bearing the emotional weight of EOL care; (4) Challenges in Protecting Patients’ Rights, characterized by powerlessness in the face of silent patients and confusion from reversed decisions by families; and (5) Actualizing Compassionate EOL Care, ensuring dignity through purposeful actions and navigating environmental barriers to dignified care. Conclusion: We highlight the need for systematic changes in the ED to better support EOL care, including the development of culturally sensitive communication protocols, shared guidelines for decision-making, and improved collaboration between healthcare professionals. These findings provide valuable insights into enhancing EOL care in EDs. Future efforts should focus on policy changes, tailored education programs, and support systems that address the multifaceted needs of patients, families, and healthcare providers.

Myxomatous mitral valve disease (MMVD) in dogs is a heart disease that is characterized by histopathologic changes in cardiomyocytes, which ultimately result in valve degeneration and blood regurgitation due to structural changes in the heart valves. A number of studies have been conducted with the objective of identifying prognostic factors that may influence the prognosis of dogs with MMVD. Nevertheless, there is a paucity of research examining the factors that predict MMVD stage progression as defined by the American College of Veterinary Internal Medicine. The objective of this study was to examine whether there are factors associated with stage progression within one year of diagnosis in dogs diagnosed with subclinical MMVD (stage B1 or B2) using physical examination findings, clinicopathologic biomarkers, and echocardiographic markers. This is a retrospective study of veterinary practice performed at Chungbuk National University Animal Hospital. The electronic medical record of the hospital was searched to obtain clinical records of canine patients diagnosed with subclinical MMVD over an 11-year period. For each patient cohort, a logistic regression analysis was conducted. The variables were initially selected using the backward elimination method, and the optimal logistic regression model was determined by removing the independent variables with the largest variance inflation factor. Among the independent variables examined in this study, heart murmur intensity was identified as a statistically significant predictor of stage progression within one year for subclinical MMVD, a finding that aligns with those of previous studies. No other independent variables were found to be significantly associated with subclinical MMVD stage progression. This is the inaugural exploratory study to concentrate on blood test results, a relatively straightforward and quantifiable test result that can be readily obtained in primary care veterinary clinics, among the factors that may be associated with the progression of subclinical MMVD stages.

Clinical pathology, including hematology and serum chemistry, is an important indicator of biological changes. Animals for inhalation studies are kept in specific chambers and require historical data for accuracy. Age-related characteristics are essential for interpreting experimental results. This study aimed to provide historical clinical pathology data and analyze age-related trends in these parameters. We collected hematological and biochemical parameters from control groups of male and female F344 rats in the 4-, 13-, 26-, and 52-week repeated inhalation toxicity tests. The number of F344 rats from collected control groups were 24, 60, 50, and 25 males and 25, 60, 50, and 25 females in the 4-, 13-, 26-, and 52-week studies, respectively. Mean comparison, correlation analysis and simple linear regression analysis was conducted to reveal age-related trends. Neutrophil count, eosinophil count, neutrophil percentage, monocyte percentage, total protein, albumin, triglyceride, total cholesterol (TCHO) showed increasing trends, whereas lymphocyte count, lymphocyte percent, platelet count, alkaline phosphatase, albumin/globulin ratio, and inorganic phosphate showed decreasing trends in both the mean comparison and regression analyses. TCHO was considered the most affected parameter by aging in both sexes based on statistical results. In this study, we presented clinicopathological data from F344 rats for inhalation toxicity studies. We confirmed aging trends in clinicopathological parameters and identified TCHO as the parameter most affected by aging in F344 rats. These results would be helpful for inhalation research using F344 rats.

We investigated the stress-induced changes in the lipid and hormonal concentrations in plasma, including cytochrome P450 (CYP)-derived oxidative stress in the liver, and the anti-stress effect of Korean Red Ginseng (KRG) water extract in mice. Stress induction using restraint increased the levels of corticosterone (CORT), glucose, total cholesterol (TC), and low-density lipoprotein-cholesterol (LDL-C) while decreasing in the levels of insulin and high-density lipoprotein-cholesterol (HDL-C), compared with those of unstressed mice. Restraint-stress also increased the generation of reactive oxygen species (ROS) in plasma by 5.4-fold. Moreover, the stress resulted in a 2.8-fold higher production of C-reactive protein (CRP) than the control group. In addition, the catalytic activities of CYP1A2 and CYP3A4 in the liver microsomes were stimulated by 5.5- and 3.8-fold, respectively, and concomitant ROS formation was elevated by 4.3-fold in the liver extract, compared to the normal group. In contrast, the KRG treatment (5, 20, or 50 mg/kg/day) to stress-exposed 3 groups alleviated the increased CORT, TC, LDL-C, ROS, and CRP levels and restored the decreased insulin concentrations. The enhanced each ROS in the plasma and liver, and the CYP enzyme activities were also attenuated in KRG-treated mice in a concentration-dependent manner. In conclusion, these results suggest that KRG ameliorates stress-induced detrimental effects on the plasma and liver of treated mice.

Diethylbenzene (DEB) is a colorless flammable liquid composed of a benzene ring and two ethyl substituents. DEBs mostly exist as a mixture of isomers and are mainly used as intermediates and solvents occupationally. Workers may be exposed to DEB inhalation during their occupational activities including manufacturing or processing of materials; however, limited data are available on the risk assessment of DEB mixtures. In this study, male and female Wistar rats were exposed to vapors of a DEB mixture for 13-weeks (6 hr/day, 5 days/ week) at concentrations of 0, 40, 80, and 160 ppm in a whole-body inhalation chamber. Clinical signs, mean body weight, food consumption, bronchoalveolar lavage fluid (BALF), hematology, blood biochemistry, gross findings, organ weights, and microscopic findings were examined to determine the toxicity of DEB mixture. The exposure concentrations in chambers were 39.48 ± 1.13 ppm, 80.43 ± 2.06 ppm, and 160.20 ± 4.42 ppm for the low, medium, and high dose groups, respectively. No changes related to the test substance were observed, including changes in clinical observation, body weight, food consumption, BALF and blood analysis, necropsy findings, absolute and relative organ weights or histopathological analysis. Based on these results, the NOAEC (no-observed-adverse-effect-concentration) of DEB was defined as 160 ppm under the study conditions.

Cell culture is a widely used in vitro tool that enhances our understanding of cell biology, disease mechanisms, drug responses, and the development of tissue engineering. However, there are a number of important drawbacks to conventional two-dimensional (2D) cultures, such as the loss of polarity, altered cell shape, and disruption of cell-extracellular matrix connections. Alternatively, organoids are tissue-engineered, cell-based in vitro models derived from stem cells that can self-organize and differentiate into three-dimensional (3D) structures, recapitulating the morphology and functions of their in vivo counterparts. Bisphenol A (BPA), a ubiquitous industrial chemical, has recently gained recognition as an environmental hazard. Previous research has demonstrated that BPA negatively affects the integrity of the intestinal barrier by triggering programmed cell death and suppressing cell growth in human colonic epithelial cell lines. However, a 2D-based cellular study cannot represent its exposure to multicellular organs. This work investigates the impact of BPA on the structure and function of the intestinal barrier. We examine the effect of BPA on the proliferation and tight junction gene expression with two models: the HT-29 colon cancer cell line and an intestine organoid model and morphological changes of intestinal organoid (I/O). The proliferation was increased in a dose-dependent manner with I/O, but at the same concentration, BPA does not increase the significant number of HT-29 cell respectively. Proliferation-related gene and tight junction gene expression pattern was similar between HT-29 and I/O other than Claudin-4. Therefore, this study offers a more precise depiction of the functional and morphological alterations caused by BPA in comparison to traditional 2D cell cultures.

본 연구는 한국의 외국인 인재 유치 정책을 검토하고 저숙련 근로자에서 고숙련자로의 패러다임 전환이 절실히 필요함을 파악한다. 본 연구는 한국 벤처기업의 선호도를 분석하여 국제 모범 사례 와 비교함으로써 한국의 외국인 인력 정책 변화의 시급성을 강조한다. 우수 외국인 인재 유치를 위 한 정책에서 법무부와 여러 경제부처 간의 부처 간 협업의 중요성, 우수 글로벌 인재 유치를 위한 정책적 고려 강조 및 동반가족 지원 개발 촉구, 외국인 인재와 스타트업 취업 기회를 연결하는 플 랫폼 조성 등이 주요 권고 사항이다.