Reliable preclinical models for assessing drug-induced cardiotoxicity are essential to reduce the high rate of drug withdrawals during development. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising platform for such assessments due to their expression of cardiacspecific ion channels and electrophysiological properties. In this study, we investigated the effects of eight arrhythmogenic drugs—E4031, nifedipine, mexiletine, JNJ303, flecainide, moxifloxacin, quinidine, and ranolazine—on hiPSC-CMs derived from both healthy individuals and a long QT syndrome (LQTS) patient using multielectrode array systems. The results demonstrated dose-dependent changes in field potential duration and arrhythmogenic risk, with LQTS-derived hiPSC-CMs showing increased sensitivity to hERG channel blockers such as E4031. Furthermore, the study highlights the potential of hiPSC-CMs to model disease-specific cardiac responses, providing insights into genetic predispositions and personalized drug responses.Despite challenges related to the immaturity of hiPSC-CMs, their ability to recapitulate human cardiac electrophysiology makes them a valuable tool for preclinical cardiotoxicity assessments. This study underscores the utility of integrating patientderived hiPSC-CMs with advanced analytical platforms, such as multi-electrode array systems, to evaluate drug-induced electrophysiological changes. These findings reinforce the role of hiPSC-CMs in drug development, facilitating safer and more efficient screening methods while supporting precision medicine applications.

Reliable preclinical models for assessing drug-induced cardiotoxicity are essential to reduce the high rate of drug withdrawals during development. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising platform for such assessments due to their expression of cardiacspecific ion channels and electrophysiological properties. In this study, we investigated the effects of eight arrhythmogenic drugs—E4031, nifedipine, mexiletine, JNJ303, flecainide, moxifloxacin, quinidine, and ranolazine—on hiPSC-CMs derived from both healthy individuals and a long QT syndrome (LQTS) patient using multielectrode array systems. The results demonstrated dose-dependent changes in field potential duration and arrhythmogenic risk, with LQTS-derived hiPSC-CMs showing increased sensitivity to hERG channel blockers such as E4031. Furthermore, the study highlights the potential of hiPSC-CMs to model disease-specific cardiac responses, providing insights into genetic predispositions and personalized drug responses.Despite challenges related to the immaturity of hiPSC-CMs, their ability to recapitulate human cardiac electrophysiology makes them a valuable tool for preclinical cardiotoxicity assessments. This study underscores the utility of integrating patientderived hiPSC-CMs with advanced analytical platforms, such as multi-electrode array systems, to evaluate drug-induced electrophysiological changes. These findings reinforce the role of hiPSC-CMs in drug development, facilitating safer and more efficient screening methods while supporting precision medicine applications.

Reliable preclinical models for assessing drug-induced cardiotoxicity are essential to reduce the high rate of drug withdrawals during development. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising platform for such assessments due to their expression of cardiacspecific ion channels and electrophysiological properties. In this study, we investigated the effects of eight arrhythmogenic drugs—E4031, nifedipine, mexiletine, JNJ303, flecainide, moxifloxacin, quinidine, and ranolazine—on hiPSC-CMs derived from both healthy individuals and a long QT syndrome (LQTS) patient using multielectrode array systems. The results demonstrated dose-dependent changes in field potential duration and arrhythmogenic risk, with LQTS-derived hiPSC-CMs showing increased sensitivity to hERG channel blockers such as E4031. Furthermore, the study highlights the potential of hiPSC-CMs to model disease-specific cardiac responses, providing insights into genetic predispositions and personalized drug responses.Despite challenges related to the immaturity of hiPSC-CMs, their ability to recapitulate human cardiac electrophysiology makes them a valuable tool for preclinical cardiotoxicity assessments. This study underscores the utility of integrating patientderived hiPSC-CMs with advanced analytical platforms, such as multi-electrode array systems, to evaluate drug-induced electrophysiological changes. These findings reinforce the role of hiPSC-CMs in drug development, facilitating safer and more efficient screening methods while supporting precision medicine applications.

Reliable preclinical models for assessing drug-induced cardiotoxicity are essential to reduce the high rate of drug withdrawals during development. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising platform for such assessments due to their expression of cardiacspecific ion channels and electrophysiological properties. In this study, we investigated the effects of eight arrhythmogenic drugs—E4031, nifedipine, mexiletine, JNJ303, flecainide, moxifloxacin, quinidine, and ranolazine—on hiPSC-CMs derived from both healthy individuals and a long QT syndrome (LQTS) patient using multielectrode array systems. The results demonstrated dose-dependent changes in field potential duration and arrhythmogenic risk, with LQTS-derived hiPSC-CMs showing increased sensitivity to hERG channel blockers such as E4031. Furthermore, the study highlights the potential of hiPSC-CMs to model disease-specific cardiac responses, providing insights into genetic predispositions and personalized drug responses.Despite challenges related to the immaturity of hiPSC-CMs, their ability to recapitulate human cardiac electrophysiology makes them a valuable tool for preclinical cardiotoxicity assessments. This study underscores the utility of integrating patientderived hiPSC-CMs with advanced analytical platforms, such as multi-electrode array systems, to evaluate drug-induced electrophysiological changes. These findings reinforce the role of hiPSC-CMs in drug development, facilitating safer and more efficient screening methods while supporting precision medicine applications.

Reliable preclinical models for assessing drug-induced cardiotoxicity are essential to reduce the high rate of drug withdrawals during development. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising platform for such assessments due to their expression of cardiacspecific ion channels and electrophysiological properties. In this study, we investigated the effects of eight arrhythmogenic drugs—E4031, nifedipine, mexiletine, JNJ303, flecainide, moxifloxacin, quinidine, and ranolazine—on hiPSC-CMs derived from both healthy individuals and a long QT syndrome (LQTS) patient using multielectrode array systems. The results demonstrated dose-dependent changes in field potential duration and arrhythmogenic risk, with LQTS-derived hiPSC-CMs showing increased sensitivity to hERG channel blockers such as E4031. Furthermore, the study highlights the potential of hiPSC-CMs to model disease-specific cardiac responses, providing insights into genetic predispositions and personalized drug responses.Despite challenges related to the immaturity of hiPSC-CMs, their ability to recapitulate human cardiac electrophysiology makes them a valuable tool for preclinical cardiotoxicity assessments. This study underscores the utility of integrating patientderived hiPSC-CMs with advanced analytical platforms, such as multi-electrode array systems, to evaluate drug-induced electrophysiological changes. These findings reinforce the role of hiPSC-CMs in drug development, facilitating safer and more efficient screening methods while supporting precision medicine applications.

Proximal femoral cephalomedullary nailing is one of the treatments of choice for intertrochanteric fracture. Zimmer Natural Nail® (ZNN; Zimmer) is one of the alternatives. We report two cases of broken tail portion of the ZNN lag screw during the removal procedure. This may be the first reported cases in scientific literature with this pattern of failure. We report these cases to highlight one of the possible problems that could occur during removal of this implant which can possibly prolong the operation time significantly if the required device is not prepared.
Hip Fractures ; Tail*

Proximal femoral cephalomedullary nailing is one of the treatments of choice for intertrochanteric fracture. Zimmer Natural Nail® (ZNN; Zimmer) is one of the alternatives. We report two cases of broken tail portion of the ZNN lag screw during the removal procedure. This may be the first reported cases in scientific literature with this pattern of failure. We report these cases to highlight one of the possible problems that could occur during removal of this implant which can possibly prolong the operation time significantly if the required device is not prepared.
Hip Fractures ; Tail*

Pulmonary edema is a major cause of mortality due to acute lung injury (ALI). The involvement of protein kinase C-delta (PKC-delta) in ALI has been a controversial topic. Here we investigated PKC-delta function in ALI using PKC-delta knockout (KO) mice and PKC inhibitors. Our results indicated that although the ability to produce proinflammatory mediators in response to LPS injury in PKC-delta KO mice was similar to that of control mice, they showed enhanced recruitment of neutrophils to the lung and more severe pulmonary edema. PKC-delta inhibition promoted barrier dysfunction in an endothelial cell layer in vitro, and administration of a PKC-delta-specific inhibitor significantly increased steady state vascular permeability. A neutrophil transmigration assay indicated that the PKC-delta inhibition increased neutrophil transmigration through an endothelial monolayer. This suggests that PKC-delta inhibition induces structural changes in endothelial cells, allowing extravasation of proteins and neutrophils.
Acute Lung Injury* ; Animals ; Capillary Permeability* ; Endothelial Cells ; Lung ; Mice ; Mortality ; Neutrophils ; Protein Kinase C-delta* ; Protein Kinases* ; Pulmonary Edema

Schistosomiasis and intestinal worm infections are widespread diseases of public health importance in Tanzania. A study on perceptions and practices related to schistosomiasis and intestinal worm infections was undertaken among a community population of Kome Island in Sengerema District, north-western Tanzania, where intestinal schistosomiasis and intestinal worm infections are endemic. Schistosomiasis and intestinal worm-related perceptions and practices were assessed before and 3 years after implementation of a participatory hygiene and sanitation transformation (PHAST) intervention as a control measure. Data were obtained from baseline and post-intervention knowledge, attitudes, and practices (KAP) questionnaire surveys conducted twice in 2009 and 2012 among 82 individuals aged > or =15 years. We found significant increases in respondents' knowledge of the cause, transmission, symptoms, health consequences, and prevention of schistosomiasis and intestinal worm infections after PHAST intervention. The increase in respondents' knowledge on almost all aspects of the said infections was translated into actions to control schistosomiasis and intestinal worm infections. This has not been achieved by chance, but due to well-designed and locally-adapted PHAST intervention. We conclude that despite criticisms, PHAST approach is still useful in empowering communities to control water, sanitation, and hygiene related infectious diseases such as schistosomiasis and intestinal worm infections.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Communicable Disease Control/*methods ; Disease Transmission, Infectious/prevention & control ; Endemic Diseases/*prevention & control ; Female ; *Health Knowledge, Attitudes, Practice ; Helminthiasis/*epidemiology/*prevention & control/psychology ; Humans ; Intestinal Diseases, Parasitic/*epidemiology/*prevention & control/psychology ; Islands ; Lakes ; Male ; Middle Aged ; Schistosomiasis/*epidemiology/*prevention & control/psychology ; Surveys and Questionnaires ; Tanzania/epidemiology ; Young Adult

Research on micro-level assessment of the changes of socio-economic status following health interventions is very scarce. The use of household asset data to determine wealth indices is a common procedure for estimating socio-economic position in resource poor settings. In such settings information about income is usually lacking, and the collection of individual consumption or expenditure data would require in-depth interviews, posing a considerable risk of bias. In this study, we determined the socio-economic status of 213 households in a community population in an island in the north-western Tanzania before and 3 year after implementation of a participatory hygiene and sanitation transformation (PHAST) intervention to control schistosomiasis and intestinal worm infections. We constructed a household 'wealth index' based housing construction features (e.g., type of roof, walls, and floor) and durable assets ownership (e.g., bicycle, radio, etc.). We employed principal components analysis and classified households into wealth quintiles. The study revealed that asset variables with positive factor scores were associated with higher socio-economic status, whereas asset variables with negative factor scores were associated with lower socio-economic status. Overall, households which were rated as the poorest and very poor were on the decrease, whereas those rated as poor, less poor, and the least poor were on the increase after PHAST intervention. This decrease/increase was significant. The median shifted from -0.4376677 to 0.5001073, and the mean from -0.2605787 (SD; 2.005688) to 0.2605787 (SD; 1.831199). The difference in socio-economic status of the people between the 2 phases was highly statistically significant (P<0.001). We argue that finding of this study should be treated with caution as there were other interventions to control schistosomiasis and intestinal worm infections which were running concurrently on Kome Island apart from PHAST intervention.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Animals ; Communicable Disease Control/*methods ; Endemic Diseases/*prevention & control ; Family Characteristics ; Female ; Helminthiasis/drug therapy/*epidemiology/*prevention & control ; Humans ; Intestinal Diseases, Parasitic/drug therapy/*epidemiology/*prevention & control ; Islands ; Lakes ; Male ; Middle Aged ; Schistosomiasis/drug therapy/*epidemiology/*prevention & control ; Social Class ; Tanzania/epidemiology ; Treatment Outcome ; Young Adult