A contemporary systematic review on liver transplantation for unresectable liver metastases of colorectal cancer

The 5-year overall survival rate of a patient with unresectable metastatic colorectal cancer is poor at approximately 14%. Similarly, historical data on liver transplantation (LT) in those with colorectal liver metastases (CRLM) showed poor outcomes, with 5-year survival rates between 12% and 21%. More recently, limited data have shown improved outcomes in select patients with 5-year overall survival rates of approximately 60%. Despite these reported survival improvements, there is no significant improvement in disease-free survival. Given the uncertain benefit with this therapeutic approach and a renewed investigational interest, we aimed to conduct a contemporary systematic review on LT for CRLM. A systematic review of the literature was performed according to the preferred reporting items for systematic reviews and meta-analysis statement. English articles reporting on data regarding LT for CRLM were identified through the MEDLINE (via PubMed), Cochrane Library, and ClinicalTrials.gov databases (last search date: December 16th, 2021) by 2 researchers independently. A total of 58 studies (45 published and 13 ongoing) were included. Although early retrospective studies suggest the possibility that some carefully selected patients may benefit from LT, there is minimal prospective data on the topic and LT remains exploratory in the setting of CRLM. Additionally, several other challenges, such as the limited availability of deceased donor organs and defining appropriate selection criteria, remain when considering the implementation of LT for these patients. Further evidence from ongoing prospective trials is needed to determine if and to what extent there is a role for LT in patients with surgically unresectable CRLM.     

The skills gap in nursing management in South Africa: a sectoral analysis: a research paper

pillay r . (2010) Journal of Nursing Management  18, 134–144
The skills gap in nursing management in South Africa: a sectoral analysis: a research paper Aim To identify competencies important for effective nursing management and to assess managers’ proficiency therein. Background A lack of management capacity has been identified as the key stumbling block to health delivery in South Africa. Despite nursing managers being central to overcoming the challenges facing health care, there has been a paucity of research that empirically evaluates their skill levels. Methods A survey was conducted among 171 senior nursing managers in South Africa using a self-administered questionnaire. Results Public sector managers assessed themselves as being relatively less competent than private sector managers. The largest skill gaps for public sector managers were for ‘ethico–legal’, ‘task-related’ and ‘controlling’ skills whereas those for private sector managers were for ‘ethico–legal’, ‘health-related ‘ and ‘task-related’ skills. Conclusions This research confirmed the lack of management capacity within the health sector and identified areas in which the skills deficit was most significant for both the public and private sectors. Implications for nursing management These findings reflect the needs of nursing managers and will be useful in the conceptualization, design and delivery of health management programmes aimed at enhancing management and leadership capacity in the health sector in South Africa.     

The role of inflammation in regulating platelet production and function: Toll-like receptors in platelets and megakaryocytes

Platelets have been extensively studied as hemostatic regulators, stopping uncontrolled flow of blood from an injured vessel and allowing for repair. However, multiple studies have shown that platelets can interact with bacterial proteins, particularly seen during sepsis and inflammation. Immune cells recognize pathogens through Toll-like Receptors (TLRs). These same receptors allow platelets to recognize bacterial proteins and regulate platelet immunity and function. This review examines the TLRs expressed on platelets and megakaryocytes and how these receptors affect the function of these cells. Through TLRs, platelets go beyond hemostatic regulation and play a pivotal role in inflammation and infection.     

In vitro metabolic characterization, phenotyping, and kinetic studies of 9cUAB30, a retinoid X receptor-specific retinoid.

The present study was conducted to compare the in vitro phase I and phase II metabolic profiles of (2E,4E,6Z,8E)-8-(3',4'-dihydro-1'(2'H)-naphthalen-1'-ylidene)-3,7-dimethyl-2,4,6-octatrienoic acid (9cUAB30) in human, rat, and dog microsomes and to characterize and identify the associated metabolic kinetics and specific isozymes from human liver microsomes (HLM) responsible for metabolism, respectively. Data from these experiments revealed that nine (M1-M9) phase I metabolites along with a single glucuronide conjugate were observed across the species investigated. With the exception of glucuronidation, no evidence of metabolism was detected for phase II enzymes (data not shown). Significant differences between species with regard to metabolic profile, stability, and gender were noted. For the eight phase I metabolites detected in HLM, the specific isozymes responsible for the biotransformations were CYP2C8, CYP2C9, and CYP2C19, with minor contributions from CYP1A2 and CYP2B6. For the glucuronide conjugate, UGT1A9 was the major catalyzing enzyme, with a minor contribution from UGT1A3. Kinetic analysis of eight of the detected metabolites indicated that four seemed to follow classical hyperbolic kinetics, whereas the remaining four showed evidence of either autoactivation or substrate inhibition.     

Metastasis of mouse T lymphoma cells is controlled by the level of major histocompatibility complex class I H-2DK antigens

In vivo inoculation of a low metastatic BW 5147 derived T-cell lymphoma variant into syngeneic mice, had led to the generation of a highly metastatic variant. The shift towards a more metastatic phenotype is accompanied by an increase in major histocompatibility class I H-2D^k antigen expression. This suggests that H-2D^k antigens may control the metastatic potential of BW T lymphoma cells. Our present findings indicate that H-2D^k expression is directly correlated with the metastatic potential of BW cells. We have confirmed such correlation by specifically altering the level of H-2D^k expression by: I) FACS analysis, 2) IFN-_γ treatment, 3) H-2D^k gene transfection. Cells sorted for low H-2D^k expression had a significantly reduced metastatic potential. Induction of H-2D^k expression on these cells by either IFN-_γ treatment or H-2D^k gene transfection concomitantly led to increased metastasis. We also assessed metastatic potential of BW cells in irradiated, immunocompromised recipients. Our results show that the immune system is implicated and we further tested which immune effectors are involved, In vivo depletion of natural killer (NK) and CD8⁺ T-cells revealed that the difference in metastatic potential of the H-2D^k variants relies upon an NK-dependent mechanism, whereas CD8⁺ T-cells are not implicated. Our observations suggest that highly metastatic cells, expressing a high level of H-2D^k antigens are more resistant to NK-cell-mediated cytotoxicity in vivo. We have confirmed our in vivo results by in vitro cytotoxicity assays using poly I:C induced NK and IL-2 activated LAK cells. We conclude that a NK-dependent mechanism accounts for the association between differential H-2D^k antigen expression and metastasis.     

Maternal phenylketonuria. Problems in detecting and risk educating identified females]

Maternal PKU is an embryo-fetopathy caused by elevated plasmaphenylalanine levels in pregnant women with hyperphenylalaninemia and phenylketonuira. Leading symptoms are microcephaly, mental retardatioin and congenital malformations, especially congenital heart disease. Maternal PKU becomes more important since early treated and normally developed girls with PKU are reaching their reproductive age in increasing numbers. There is a lack of adequate knowledge about the dangers of maternal PKU in at-risk women. Only 43% of these women in the Federal Republic of Germany are located by now and can be informed and instructed. Ways and conditions of tracking are described.     

A Community-Based Approach to the Promotion of Breastfeeding in Mexico

A comprehensive education strategy is presented that links training, community education, research, and mass-media efforts to enhance breastfeeding practices. Breastfeeding promotion models, an administrative system, and lessons learned during the project are described. The keys to effective breastfeeding promotion are shown to be accurate information; appropriate education, training, and follow-up; and a supportive administrative system.     

Laser Lipolysis: Flaccidity Under Control

An innovative liposuction technique using a laser device is presented. It is a precise method, less traumatic than the conventional one. The interaction between the laser and the adipocyte causes lipolysis with reduced bleeding and its effect on collagen tone promotes collagen retraction and skin shrinkage. The results of the use of laser lipolysis on flaccid areas or in areas with the potencial for flaccidity are shown. The resulting skin retraction and the pathologic anatomy confirm these claims.