The Pictorial Fit-Frail Scale Malay Version (PFFS-M): Predictive Validity Testing in Malaysian Primary Care.

The purpose of this study was to evaluate the association between Pictorial Fit Frail Scale-Malay version (PFFS-M) and adverse outcomes, such as falls, new disability, hospitalisation, nursing home placement, and/or mortality, in patients aged 60 and older attending Malaysian public primary care clinics. We assessed the baseline PFFS-M levels of 197 patients contactable by phone at 18 months to determine the presence of adverse outcomes. 26 patients (13.2%) reported at least one adverse outcome, including five (2.5%) who fell, three (1.5%) who became disabled and homebound, 15 (7.6%) who were hospitalized, and three (1.5%) who died. Using binary multivariable logistic regression adjusted for age and gender, we found that patients who were at-risk of frailty and frail at baseline were associated with 5.97(95% CI [1.89-18.91]; P=0.002) and 6.13 (95% CI [1.86-20.24]; P= 0.003) times higher risk of developing adverse outcomes at 18 months, respectively, than patients who were not frail. The PFFS-M was associated with adverse outcomes.

Identification of levomenthol derivatives as potential dipeptidyl peptidase-4 inhibitors: a comparative study with gliptins.

Dipeptidyl peptidase-4 (DPP4) inhibitors are a potent therapeutic treatment for type 2 diabetes mellitus (T2DM). There is a family of compounds used as DPP4 inhibitors (DPP4Is) called gliptins. They bind tightly to DPP4 to form an inactive protein-ligand complex. However, there remains a need to identify novel DPP4Is that are more efficacious and safer due to the increasing prevalence of T2DM and the undesirable side effects of gliptins. To identify potential DPP4Is, we screened over 1800 novel compounds in a comparative study with gliptins. We performed dual-factor molecular docking to assess the binding affinity of the compounds to DPP4 and found four compounds with a higher binding affinity to DPP4 than currently used gliptins. The newly identified compounds interacted with the dyad glutamate (GLU205 and GLU206) and tyrosine (TYR662 and TYR666) residues in DPP4's active site. We performed molecular dynamics simulations to determine the stability of the protein-ligand complexes formed by the compounds and DPP4. Furthermore, we examined the toxicity and pharmacological profile of the compounds. The compounds are drug-like, easy to synthesize, and relatively less toxic than gliptins. Collectively, our results suggest that the novel compounds are potential DPP4Is and should be considered for further studies to develop novel antidiabetics.Communicated by Ramaswamy H. Sarma.

Boosting Live Malaria Vaccine with Cytomegalovirus Vector Can Prolong Immunity through Innate and Adaptive Mechanisms.

Vaccines to persistent parasite infections have been challenging, and current iterations lack long-term protection. Cytomegalovirus (CMV) chronic vaccine vectors drive protection against SIV, tuberculosis and liver-stage malaria correlated with antigen-specific CD8 T cells with a Tem phenotype. This phenotype is likely driven by a combination of antigen-specific and innate adjuvanting effects of the vector, though these mechanisms are less well understood. Sterilizing immunity from live Plasmodium chabaudi vaccination lasts less than 200 days. While P. chabaudi-specific antibody levels remain stable after vaccination, the decay of parasite-specific T cells correlates with loss of challenge protection. Therefore, we enlisted murine CMV as a booster strategy to prolong T cell responses against malaria. To study induced T cell responses, we included P. chabaudi MSP-1 epitope B5 (MCMV-B5). We found that MCMV vector alone significantly protected against a challenge P. chabaudi infection 40-60 days later, and that MCMV-B5 was able to make B5-specific Teff, in addition to previously-reported Tem, that survive to the challenge timepoint. Used as a booster, MCMV-B5 prolonged protection from heterologous infection beyond day 200, and increased B5 TCR Tg T cell numbers, including both a highly-differentiated Tem phenotype and Teff, both previously reported to protect. B5 epitope expression was responsible for maintenance of Th1 and Tfh B5 T cells. In addition, the MCMV vector had adjuvant properties, contributing non-specifically through prolonged stimulation of IFN-γ. In vivo neutralization of IFN-γ, but not IL-12 and IL-18, late in the course of MCMV, led to loss of the adjuvant effect. Mechanistically, sustained IFN-γ from MCMV increased CD8α+ dendritic cell numbers, and led to increased IL-12 production upon Plasmodium challenge. In addition, neutralization of IFN-γ before challenge reduced the polyclonal Teff response to challenge. Our findings suggest that, as protective epitopes are defined, an MCMV vectored booster can prolong protection through the innate effects of IFN-γ.

Complete Heparin Reversal by Protamine during Off-Pump Coronary Artery Bypass Surgery (OPCAB): A Necessity or Myth?

In our country majority of the coronary artery bypass surgery (CABG) are done off-pump and was reported having excellent clinical outcome along with cost efficiency by various investigators. Heparin is commonly used as most effective anticoagulant, and protamine sulfate is now generally used to reverse the anticoagulant action of heparin. While under dosing of protamine may result in incomplete heparin reversal and prolonged anticoagulation, protamine overdosing is associated with impaired clot formation exerted by the intrinsic anti-coagulation properties of protamine itself, moreover protamine administration is associated with mild to severe cardiovascular and pulmonary complications. Apart from traditional full neutralization of heparin now-a-days, half dose protamine was also introduced showing good outcome regarding lower activated clotting time (ACT), overall, less surgical bleeding with less transfusion. This comparative study was designed to detect differences between traditional and decreased protamine dosing in Off-Pump Coronary Artery Bypass (OPCAB) surgery. Four hundred (400) patients who underwent Off-Pump Coronary Artery Bypass Surgery (OPCAB) surgery at our institution over a period of 12 months were analyzed and were divided into two groups. Group A- received 0.5mg of protamine per 100 unit of heparin; Group B-received 1.0mg of protamine per 100 unit of heparin. ACT, blood loss, hemoglobin and platelet count units of blood and blood product transfusion requirements, clinical outcome and hospital stay were assessed in each patient. This study showed that 0.5mg of protamine per 100 unit of heparin was always able to reverse the anticoagulant effect of heparin with no significant difference in hemodynamic parameters, amount of blood loss and requirements of blood transfusion in between the groups. A standard protamine dosing formula (protamine-heparin at ratio of 1:1) adequate for on-pump cardiac surgical procedures significantly overestimates protamine requirements for OPCAB. Patients treated with decreased protamine do not appear to have adverse outcomes in terms of post-operative bleeding.

Effects of Low-Level Persistent Infection on Maintenance of Immunity by CD4 T Cell Subsets and Th1 Cytokines.

CD4 T cells are required, along with antibodies, for complete protection from blood-stage infection with Plasmodium spp., which cause malaria. Without continuous exposure, as on emigration of people from endemic areas, protection from malaria decays. As in other persistent infections, low-level Plasmodium chabaudi infection protects the host from reinfection at 2 months postinfection, a phenomenon termed premunition. Premunition is correlated with T cell responses, rather than antibody levels. We previously showed that while both effector T cells (Teff) and memory T cells (Tmem) are present after infection, Teff protect better than Tmem. Here, we studied T cell kinetics post-infection by labeling dividing Ifng+ T cells with 5-bromo-2'-deoxyuridine (BrdU) in infected Ifng reporter mice. Large drops in specific T cell numbers and Ifng+ cells upon clearance of parasites suggest a mechanism for decay of protection. Although protection decays, CD4 Tmem persist, including a highly differentiated CD27- effector memory (Tem) subset that maintains some Ifng expression. In addition, pretreatment of chronically infected animals with neutralizing antibody to interferon gamma (IFN-γ) or with clodronate liposomes before reinfection decreases premunition, supporting a role for Th1-type immunity to reinfection. A pulse-chase experiment comparing chronically infected to treated animals showed that recently divided Ifng+ T cells, particularly IFN-γ+ TNF+ IL-2- T cells, are promoted by persistent infection. These data suggest that low-level persistent infection reduces CD4+ Tmem and multifunctional Teff survival, but promotes IFN-γ+ TNF+ IL-2- T cells and Ifng+ terminally differentiated effector T cells, and prolongs immunity.

Toxicological effects of thimerosal on rat kidney: a histological and biochemical study / Efeitos toxicológicos do timerosal no rim de rato: um estudo histológico e bioquímico

Thimerosal is an organomercurial compound, which is used in the preparation of intramuscular immunoglobulin, antivenoms, tattoo inks, skin test antigens, nasal products, ophthalmic drops, and vaccines as a preservative. In most of animal species and humans, the kidney is one of the main sites for mercurial compounds deposition and target organs for toxicity. So, the current research was intended to assess the thimerosal induced nephrotoxicity in male rats. Twenty-four adult male albino rats were categorized into four groups. The first group was a control group. Rats of Group-II, Group-III, and Group-IV were administered with 0.5µg/kg, 10µg/kg, and 50µg/kg of thimerosal once a day, respectively. Thimerosal administration significantly decreased the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione reductase (GR), glutathione (GSH), and protein content while increased the thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H2O2) levels dose-dependently. Blood urea nitrogen (BUN), creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, urinary albumin and creatinine clearance was reduced dose-dependently in thimerosal treated groups. The results demonstrated that thimerosal significantly increased the inflammation indicators including nuclear factor kappaB (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activities, DNA and histopathological damages dose-dependently. So, the present findings ascertained that thimerosal exerted nephrotoxicity in male albino rats.

O timerosal é um composto organomercurial, utilizado na preparação de imunoglobulina intramuscular, antivenenos, tintas de tatuagem, antígenos de teste cutâneo, produtos nasais, gotas oftálmicas e vacinas como conservante. Na maioria das espécies animais e nos humanos, o rim é um dos principais locais de deposição de compostos de mercúrio e órgãos-alvo de toxicidade. Assim, a presente pesquisa teve como objetivo avaliar a nefrotoxicidade induzida pelo timerosal em ratos machos. Vinte e quatro ratos albinos machos adultos foram categorizados em quatro grupos. O primeiro grupo era um grupo de controle. Ratos do Grupo II, Grupo III e Grupo IV receberam 0,5µg / kg, 10µg / kg e 50µg / kg de timerosal uma vez ao dia, respectivamente. A administração de timerosal diminuiu significativamente as atividades de catalase (CAT), superóxido dismutase (SOD), peroxidase (POD), glutationa redutase (GR), glutationa (GSH) e conteúdo de proteína, enquanto aumentou as substâncias reativas ao ácido tiobarbitúrico (TBARS) e peróxido de hidrogênio (H2O2) níveis dependentes da dose. Os níveis de nitrogênio ureico no sangue (BUN), creatinina, urobilinogênio, proteínas urinárias, molécula de lesão renal-1 (KIM-1) e lipocalina associada à gelatinase de neutrófilos (NGAL) aumentaram substancialmente. Em contraste, a albumina urinária e a depuração da creatinina foram reduzidas de forma dependente da dose nos grupos tratados com timerosal. Os resultados demonstraram que o timerosal aumentou significativamente os indicadores de inflamação, incluindo fator nuclear kappaB (NF-κB), fator de necrose tumoral-α (TNF-α), interleucina-1β (IL-1β), níveis de interleucina-6 (IL-6) e atividades da ciclooxigenase-2 (COX-2), DNA e danos histopatológicos dependentes da dose. Portanto, os presentes achados verificaram que o timerosal exerceu nefrotoxicidade em ratos albinos machos.

Mitigation of cisplatin induced nephrotoxicity by casticin in male albino rats / Mitigação da nefrotoxicidade induzida pela cisplatina pela casticina em ratos albinos machos

Cisplatin (CP) is a commonly used, powerful antineoplastic drug, having numerous side effects. Casticin (CAS) is considered as a free radical scavenger and a potent antioxidant. The present research was planned to assess the curative potential of CAS on CP persuaded renal injury in male albino rats. Twenty four male albino rats were distributed into four equal groups. Group-1 was considered as a control group. Animals of Group-2 were injected with 5mg/kg of CP intraperitoneally. Group-3 was co-treated with CAS (50mg/kg) orally and injection of CP (5mg/kg). Group-4 was treated with CAS (50mg/kg) orally throughout the experiment. CP administration substantially reduced the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione S-transferase (GST), glutathione reductase (GSR), glutathione (GSH) content while increased thiobarbituric acid reactive substances (TBARS), and hydrogen peroxide (H2O2) levels. Urea, urinary creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, albumin and creatinine clearance was significantly reduced in CP treated group. The results demonstrated that CP significantly increased the inflammation indicators including nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activity and histopathological damages. However, the administration of CAS displayed a palliative effect against CP-generated renal toxicity and recovered all parameters by bringing them to a normal level. These results revealed that the CAS is an effective compound having the curative potential to counter the CP-induced renal damage.

A cisplatina (CP) é uma droga antineoplásica poderosa, comumente usada, com vários efeitos colaterais. Casticin (CAS) é considerado um eliminador de radicais livres e um potente antioxidante. A presente pesquisa foi planejada para avaliar o potencial curativo da CAS em lesão renal induzida por PC em ratos albinos machos. Vinte e quatro ratos albinos machos foram distribuídos em quatro grupos iguais. O Grupo 1 foi considerado grupo controle. Os animais do Grupo 2 foram injetados com 5 mg / kg de PB por via intraperitoneal. O Grupo 3 foi cotratado com CAS (50 mg / kg) por via oral e injeção de CP (5 mg / kg). O Grupo 4 foi tratado com CAS (50 mg / kg) por via oral durante todo o experimento. A administração de CP reduziu substancialmente as atividades de catalase (CAT), superóxido dismutase (SOD), peroxidase (POD), glutationa S-transferase (GST), glutationa redutase (GSR), glutationa (GSH), enquanto aumentou as substâncias reativas ao ácido tiobarbitúrico (TBARS) e níveis de peróxido de hidrogênio (H2O2). Os níveis de ureia, creatinina urinária, urobilinogênio, proteínas urinárias, molécula 1 de lesão renal (KIM-1) e lipocalina associada à gelatinase de neutrófilos (NGAL) aumentaram substancialmente. Em contraste, a albumina e a depuração da creatinina foram significativamente reduzidas no grupo tratado com PC. Os resultados demonstraram que a CP aumentou significativamente os indicadores de inflamação, incluindo fator nuclear kappa-B (NF-κB), fator de necrose tumoral-α (TNF-α), interleucina-1β (IL-1β), interleucina-6 (IL-6) níveis e atividade da ciclooxigenase-2 (COX-2) e danos histopatológicos. No entanto, a administração de CAS apresentou um efeito paliativo contra a toxicidade renal gerada por CP e recuperou todos os parâmetros, trazendo-os a um nível normal. Estes resultados revelaram que o CAS é um composto eficaz com potencial curativo para combater o dano renal induzido por CP.

Enterotoxigenic methicillin resistant Staphylococcus aureus contamination in salted fish from Gwadar Balochistan / Contaminação de Staphylococcus aureus resistente à meticilina enterotoxigênica em peixes salgados de Gwadar Balochistan

Staphylococcus aureus is an important foodborne pathogen associated to food intoxication and other multiple infections in human being. Its presence in salted food is a serious issue due to its salt tolerance potential. A study was conducted to analyze the presence of enterotoxins producing drug resistance S. aureus in salted sea fish from Gwadar. Freshly persevered samples (n=50) of salted fish were subjected to analyze the presence of S. aureus using 16S rRNA and Nuc genes primers. The isolates were then evaluated for drug resistance and enterotoxins producing potential using specific primers for MecA (methicillin resistance gene), (SEA) staphylococcal enterotoxin A and (SEB) staphylococcal enterotoxin B genes. Total 13/50 (26%) of the samples were found positive for the presence of S. aureus, preliminary confirmed with biochemical profiling and finally with the help of target genes presence. The isolates were found showing 100% resistant to methicillin, which were molecularly confirmed by the presence of MecA gene present in genome. The isolates 5/13 (38%) were positive for SEA and 3/13 (23%) for SEB genes, whereas 2/13 (15%) were confirmed having both SEA and SEB genes in its genome. It was also confirmed that all the isolates were capable to form biofilm over the glass surfaces. It was concluded that the study confirmed the presence of enterotoxigenic methicillin resistance Staphylococcus aurous (MRSA) in salted fish product, that poses gross food safety concern. Preventive and control measures are necessary to handle this serious food safety concern.

Staphylococcus aureus é um importante patógeno de origem alimentar associado à intoxicação alimentar e outras infecções múltiplas em seres humanos. Sua presença em alimentos salgados é um problema sério devido ao seu potencial de tolerância ao sal. Um estudo foi realizado para analisar a presença de enterotoxinas produtoras de resistência a drogas S. aureus em peixes salgados do mar de Gwadar. Amostras recém-perseveradas (n = 50) de peixes salgados foram submetidas à análise da presença de S. aureus usando os primers dos genes 16S rRNA e Nuc. Os isolados foram então avaliados quanto à resistência a drogas e potencial de produção de enterotoxinas usando primers específicos para os genes MecA (gene de resistência à meticilina), (SEA) enterotoxina A estafilocócica e (SEB) enterotoxina B estafilocócica genes. Um total de 13/50 (26%) das amostras foi considerado positivas para a presença de S. aureus, confirmadas preliminarmente com perfis bioquímicos e finalmente com a ajuda da presença de genes-alvo. Os isolados foram encontrados com 100% de resistência à meticilina, os quais foram confirmados molecularmente pela presença do gene MecA no genoma. Os isolados 5/13 (38%) foram positivos para SEA e 3/13 (23%) para genes SEB, enquanto 2/13 (15%) foram confirmados tendo os genes SEA e SEB em seu genoma. Também foi verificado que todos os isolados foram capazes de formar biofilme sobre as superfícies de vidro. Concluiu-se que o estudo confirmou a presença de Staphylococcus aurous resistente à meticilina enterotoxigênica (MRSA) em produtos de peixe salgado, o que representa uma grande preocupação para a segurança alimentar. Medidas preventivas e de controle são necessárias para lidar com essa grave preocupação com a segurança alimentar.

Toxicological effects of thimerosal on rat kidney: a histological and biochemical study

Abstract Thimerosal is an organomercurial compound, which is used in the preparation of intramuscular immunoglobulin, antivenoms, tattoo inks, skin test antigens, nasal products, ophthalmic drops, and vaccines as a preservative. In most of animal species and humans, the kidney is one of the main sites for mercurial compounds deposition and target organs for toxicity. So, the current research was intended to assess the thimerosal induced nephrotoxicity in male rats. Twenty-four adult male albino rats were categorized into four groups. The first group was a control group. Rats of Group-II, Group-III, and Group-IV were administered with 0.5µg/kg, 10µg/kg, and 50µg/kg of thimerosal once a day, respectively. Thimerosal administration significantly decreased the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione reductase (GR), glutathione (GSH), and protein content while increased the thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H2O2) levels dose-dependently. Blood urea nitrogen (BUN), creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, urinary albumin and creatinine clearance was reduced dose-dependently in thimerosal treated groups. The results demonstrated that thimerosal significantly increased the inflammation indicators including nuclear factor kappaB (NF-B), tumor necrosis factor- (TNF-), Interleukin-1 (IL-1), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activities, DNA and histopathological damages dose-dependently. So, the present findings ascertained that thimerosal exerted nephrotoxicity in male albino rats.

Resumo O timerosal é um composto organomercurial, utilizado na preparação de imunoglobulina intramuscular, antivenenos, tintas de tatuagem, antígenos de teste cutâneo, produtos nasais, gotas oftálmicas e vacinas como conservante. Na maioria das espécies animais e nos humanos, o rim é um dos principais locais de deposição de compostos de mercúrio e órgãos-alvo de toxicidade. Assim, a presente pesquisa teve como objetivo avaliar a nefrotoxicidade induzida pelo timerosal em ratos machos. Vinte e quatro ratos albinos machos adultos foram categorizados em quatro grupos. O primeiro grupo era um grupo de controle. Ratos do Grupo II, Grupo III e Grupo IV receberam 0,5µg / kg, 10µg / kg e 50µg / kg de timerosal uma vez ao dia, respectivamente. A administração de timerosal diminuiu significativamente as atividades de catalase (CAT), superóxido dismutase (SOD), peroxidase (POD), glutationa redutase (GR), glutationa (GSH) e conteúdo de proteína, enquanto aumentou as substâncias reativas ao ácido tiobarbitúrico (TBARS) e peróxido de hidrogênio (H2O2) níveis dependentes da dose. Os níveis de nitrogênio ureico no sangue (BUN), creatinina, urobilinogênio, proteínas urinárias, molécula de lesão renal-1 (KIM-1) e lipocalina associada à gelatinase de neutrófilos (NGAL) aumentaram substancialmente. Em contraste, a albumina urinária e a depuração da creatinina foram reduzidas de forma dependente da dose nos grupos tratados com timerosal. Os resultados demonstraram que o timerosal aumentou significativamente os indicadores de inflamação, incluindo fator nuclear kappaB (NF-B), fator de necrose tumoral- (TNF-), interleucina-1 (IL-1), níveis de interleucina-6 (IL-6) e atividades da ciclooxigenase-2 (COX-2), DNA e danos histopatológicos dependentes da dose. Portanto, os presentes achados verificaram que o timerosal exerceu nefrotoxicidade em ratos albinos machos.

Mitigation of cisplatin induced nephrotoxicity by casticin in male albino rats

Abstract Cisplatin (CP) is a commonly used, powerful antineoplastic drug, having numerous side effects. Casticin (CAS) is considered as a free radical scavenger and a potent antioxidant. The present research was planned to assess the curative potential of CAS on CP persuaded renal injury in male albino rats. Twenty four male albino rats were distributed into four equal groups. Group-1 was considered as a control group. Animals of Group-2 were injected with 5mg/kg of CP intraperitoneally. Group-3 was co-treated with CAS (50mg/kg) orally and injection of CP (5mg/kg). Group-4 was treated with CAS (50mg/kg) orally throughout the experiment. CP administration substantially reduced the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione S-transferase (GST), glutathione reductase (GSR), glutathione (GSH) content while increased thiobarbituric acid reactive substances (TBARS), and hydrogen peroxide (H2O2) levels. Urea, urinary creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, albumin and creatinine clearance was significantly reduced in CP treated group. The results demonstrated that CP significantly increased the inflammation indicators including nuclear factor kappa-B (NF-B), tumor necrosis factor- (TNF-), Interleukin-1 (IL-1), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activity and histopathological damages. However, the administration of CAS displayed a palliative effect against CP-generated renal toxicity and recovered all parameters by bringing them to a normal level. These results revealed that the CAS is an effective compound having the curative potential to counter the CP-induced renal damage.

Resumo A cisplatina (CP) é uma droga antineoplásica poderosa, comumente usada, com vários efeitos colaterais. Casticin (CAS) é considerado um eliminador de radicais livres e um potente antioxidante. A presente pesquisa foi planejada para avaliar o potencial curativo da CAS em lesão renal induzida por PC em ratos albinos machos. Vinte e quatro ratos albinos machos foram distribuídos em quatro grupos iguais. O Grupo 1 foi considerado grupo controle. Os animais do Grupo 2 foram injetados com 5 mg / kg de PB por via intraperitoneal. O Grupo 3 foi cotratado com CAS (50 mg / kg) por via oral e injeção de CP (5 mg / kg). O Grupo 4 foi tratado com CAS (50 mg / kg) por via oral durante todo o experimento. A administração de CP reduziu substancialmente as atividades de catalase (CAT), superóxido dismutase (SOD), peroxidase (POD), glutationa S-transferase (GST), glutationa redutase (GSR), glutationa (GSH), enquanto aumentou as substâncias reativas ao ácido tiobarbitúrico (TBARS) e níveis de peróxido de hidrogênio (H2O2). Os níveis de ureia, creatinina urinária, urobilinogênio, proteínas urinárias, molécula 1 de lesão renal (KIM-1) e lipocalina associada à gelatinase de neutrófilos (NGAL) aumentaram substancialmente. Em contraste, a albumina e a depuração da creatinina foram significativamente reduzidas no grupo tratado com PC. Os resultados demonstraram que a CP aumentou significativamente os indicadores de inflamação, incluindo fator nuclear kappa-B (NF-B), fator de necrose tumoral- (TNF-), interleucina-1 (IL-1), interleucina-6 (IL-6) níveis e atividade da ciclooxigenase-2 (COX-2) e danos histopatológicos. No entanto, a administração de CAS apresentou um efeito paliativo contra a toxicidade renal gerada por CP e recuperou todos os parâmetros, trazendo-os a um nível normal. Estes resultados revelaram que o CAS é um composto eficaz com potencial curativo para combater o dano renal induzido por CP.

Enterotoxigenic methicillin resistant Staphylococcus aureus contamination in salted fish from Gwadar Balochistan

Abstract Staphylococcus aureus is an important foodborne pathogen associated to food intoxication and other multiple infections in human being. Its presence in salted food is a serious issue due to its salt tolerance potential. A study was conducted to analyze the presence of enterotoxins producing drug resistance S. aureus in salted sea fish from Gwadar. Freshly persevered samples (n=50) of salted fish were subjected to analyze the presence of S. aureus using 16S rRNA and Nuc genes primers. The isolates were then evaluated for drug resistance and enterotoxins producing potential using specific primers for MecA (methicillin resistance gene), (SEA) staphylococcal enterotoxin A and (SEB) staphylococcal enterotoxin B genes. Total 13/50 (26%) of the samples were found positive for the presence of S. aureus, preliminary confirmed with biochemical profiling and finally with the help of target genes presence. The isolates were found showing 100% resistant to methicillin, which were molecularly confirmed by the presence of MecA gene present in genome. The isolates 5/13 (38%) were positive for SEA and 3/13 (23%) for SEB genes, whereas 2/13 (15%) were confirmed having both SEA and SEB genes in its genome. It was also confirmed that all the isolates were capable to form biofilm over the glass surfaces. It was concluded that the study confirmed the presence of enterotoxigenic methicillin resistance Staphylococcus aurous (MRSA) in salted fish product, that poses gross food safety concern. Preventive and control measures are necessary to handle this serious food safety concern.

Resumo Staphylococcus aureus é um importante patógeno de origem alimentar associado à intoxicação alimentar e outras infecções múltiplas em seres humanos. Sua presença em alimentos salgados é um problema sério devido ao seu potencial de tolerância ao sal. Um estudo foi realizado para analisar a presença de enterotoxinas produtoras de resistência a drogas S. aureus em peixes salgados do mar de Gwadar. Amostras recém-perseveradas (n = 50) de peixes salgados foram submetidas à análise da presença de S. aureus usando os primers dos genes 16S rRNA e Nuc. Os isolados foram então avaliados quanto à resistência a drogas e potencial de produção de enterotoxinas usando primers específicos para os genes MecA (gene de resistência à meticilina), (SEA) enterotoxina A estafilocócica e (SEB) enterotoxina B estafilocócica genes. Um total de 13/50 (26%) das amostras foi considerado positivas para a presença de S. aureus, confirmadas preliminarmente com perfis bioquímicos e finalmente com a ajuda da presença de genes-alvo. Os isolados foram encontrados com 100% de resistência à meticilina, os quais foram confirmados molecularmente pela presença do gene MecA no genoma. Os isolados 5/13 (38%) foram positivos para SEA e 3/13 (23%) para genes SEB, enquanto 2/13 (15%) foram confirmados tendo os genes SEA e SEB em seu genoma. Também foi verificado que todos os isolados foram capazes de formar biofilme sobre as superfícies de vidro. Concluiu-se que o estudo confirmou a presença de Staphylococcus aurous resistente à meticilina enterotoxigênica (MRSA) em produtos de peixe salgado, o que representa uma grande preocupação para a segurança alimentar. Medidas preventivas e de controle são necessárias para lidar com essa grave preocupação com a segurança alimentar.

Toxicological effects of thimerosal on rat kidney: a histological and biochemical study.

Thimerosal is an organomercurial compound, which is used in the preparation of intramuscular immunoglobulin, antivenoms, tattoo inks, skin test antigens, nasal products, ophthalmic drops, and vaccines as a preservative. In most of animal species and humans, the kidney is one of the main sites for mercurial compounds deposition and target organs for toxicity. So, the current research was intended to assess the thimerosal induced nephrotoxicity in male rats. Twenty-four adult male albino rats were categorized into four groups. The first group was a control group. Rats of Group-II, Group-III, and Group-IV were administered with 0.5µg/kg, 10µg/kg, and 50µg/kg of thimerosal once a day, respectively. Thimerosal administration significantly decreased the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione reductase (GR), glutathione (GSH), and protein content while increased the thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H2O2) levels dose-dependently. Blood urea nitrogen (BUN), creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, urinary albumin and creatinine clearance was reduced dose-dependently in thimerosal treated groups. The results demonstrated that thimerosal significantly increased the inflammation indicators including nuclear factor kappaB (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activities, DNA and histopathological damages dose-dependently. So, the present findings ascertained that thimerosal exerted nephrotoxicity in male albino rats.

Mitigation of cisplatin induced nephrotoxicity by casticin in male albino rats.

Cisplatin (CP) is a commonly used, powerful antineoplastic drug, having numerous side effects. Casticin (CAS) is considered as a free radical scavenger and a potent antioxidant. The present research was planned to assess the curative potential of CAS on CP persuaded renal injury in male albino rats. Twenty four male albino rats were distributed into four equal groups. Group-1 was considered as a control group. Animals of Group-2 were injected with 5mg/kg of CP intraperitoneally. Group-3 was co-treated with CAS (50mg/kg) orally and injection of CP (5mg/kg). Group-4 was treated with CAS (50mg/kg) orally throughout the experiment. CP administration substantially reduced the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione S-transferase (GST), glutathione reductase (GSR), glutathione (GSH) content while increased thiobarbituric acid reactive substances (TBARS), and hydrogen peroxide (H2O2) levels. Urea, urinary creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, albumin and creatinine clearance was significantly reduced in CP treated group. The results demonstrated that CP significantly increased the inflammation indicators including nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activity and histopathological damages. However, the administration of CAS displayed a palliative effect against CP-generated renal toxicity and recovered all parameters by bringing them to a normal level. These results revealed that the CAS is an effective compound having the curative potential to counter the CP-induced renal damage.

Enterotoxigenic methicillin resistant Staphylococcus aureus contamination in salted fish from Gwadar Balochistan.

Staphylococcus aureus is an important foodborne pathogen associated to food intoxication and other multiple infections in human being. Its presence in salted food is a serious issue due to its salt tolerance potential. A study was conducted to analyze the presence of enterotoxins producing drug resistance S. aureus in salted sea fish from Gwadar. Freshly persevered samples (n=50) of salted fish were subjected to analyze the presence of S. aureus using 16S rRNA and Nuc genes primers. The isolates were then evaluated for drug resistance and enterotoxins producing potential using specific primers for MecA (methicillin resistance gene), (SEA) staphylococcal enterotoxin A and (SEB) staphylococcal enterotoxin B genes. Total 13/50 (26%) of the samples were found positive for the presence of S. aureus, preliminary confirmed with biochemical profiling and finally with the help of target genes presence. The isolates were found showing 100% resistant to methicillin, which were molecularly confirmed by the presence of MecA gene present in genome. The isolates 5/13 (38%) were positive for SEA and 3/13 (23%) for SEB genes, whereas 2/13 (15%) were confirmed having both SEA and SEB genes in its genome. It was also confirmed that all the isolates were capable to form biofilm over the glass surfaces. It was concluded that the study confirmed the presence of enterotoxigenic methicillin resistance Staphylococcus aurous (MRSA) in salted fish product, that poses gross food safety concern. Preventive and control measures are necessary to handle this serious food safety concern.

Laparoscopic colorectal resections during the COVID-19 pandemic - business as usual?

INTRODUCTION: To analyse the outcomes of major colorectal resections performed during the COVID-19 pandemic, to assess safety and explore all precautionary measures. METHOD: All patients who underwent major elective colorectal resections at St Helens and Knowsley Teaching Hospital NHS Trust between 24th March 2020 (the date that the Royal Colleges of Surgery produced their guidelines re operating during the pandemic) and 17th April 2020 were analysed from a prospectively maintained database. The primary outcome was 7-day mortality and secondary outcomes were the development of a positive COVID-19 test consequent to hospital stay and the overall complication rate. RESULTS: In this 24 day time frame 27 patients (17 males) underwent elective colorectal resections at St Helens and Knowsley NHS Trust. The median age was 69 (41-84) years and median ASA was 2 (1-3). The median Body Mass Index was 30 (21-40.7). Twenty-five patients underwent surgery for cancer and two patients had urgent resections for low-grade sepsis secondary to diverticular colovesical fistulae. 24 patients underwent laparoscopic colorectal resections and 3 patients underwent planned open surgery. 7-day mortality was 0%, and no patients/staff contracted COVID-19 during the post-operative period. The overall complication rate was 14.8%. At a median follow-up of 29 (17-44) days via telephone, there have been no reported COVID-19 related symptoms in any of these patients. CONCLUSION: Our experience demonstrated that it was possible to undertake laparoscopic colorectal resections despite the COVID-19 pandemic posing a major threat to humanity, providing that adequate and stringent precautions are undertaken.

3D Printed Minerals as Astrobiology Analogs of Hydrothermal Vent Chimneys.

Hydrothermal vents, which are highly plausible habitable environments for life and of interest for some origin-of-life scenarios, may exist on icy moons such as Europa or Enceladus in addition to Earth. Some hydrothermal vent chimney structures are extremely porous and friable, making their reconstruction in the lab challenging (e.g., brucite or saponite in alkaline hydrothermal settings). Here, we present the results from our efforts to reconstruct a simplified chimney structure directly out of mineral powder using binder jet additive manufacturing. Olivine sand was chosen for this initial method development effort since it represents a naturally occurring seafloor material and is inexpensively available in large quantities in powder form. The crystal structure of olivine used for the print was not modified during the process, as confirmed by powder X-ray diffraction (XRD). To characterize the microstructure of our 3D printed precipitates, we used computed tomography (CT) X-ray scan techniques. We also evaluated a chimney precipitate from a sample collected from the Prony Hydrothermal Field (PHF), southern New Caledonia, an alkaline system driven by serpentinization with mineralogy composed of brucite and carbonates. While not directly comparable from a mineralogical point of view, the microstructure and porosity of both precipitates was similar, suggesting that our 3D printing technique may be a valuable tool for future astrobiology research on hydrothermal vent precipitates.

Endovascular Neuromodulation: Safety Profile and Future Directions.

Endovascular neuromodulation is an emerging technology that represents a synthesis between interventional neurology and neural engineering. The prototypical endovascular neural interface is the StentrodeTM, a stent-electrode array which can be implanted into the superior sagittal sinus via percutaneous catheter venography, and transmits signals through a transvenous lead to a receiver located subcutaneously in the chest. Whilst the StentrodeTM has been conceptually validated in ovine models, questions remain about the long term viability and safety of this device in human recipients. Although technical precedence for venous sinus stenting already exists in the setting of idiopathic intracranial hypertension, long term implantation of a lead within the intracranial veins has never been previously achieved. Contrastingly, transvenous leads have been successfully employed for decades in the setting of implantable cardiac pacemakers and defibrillators. In the current absence of human data on the StentrodeTM, the literature on these structurally comparable devices provides valuable lessons that can be translated to the setting of endovascular neuromodulation. This review will explore this literature in order to understand the potential risks of the StentrodeTM and define avenues where further research and development are necessary in order to optimize this device for human application.

Evidence-based Canadian guidelines for tele-retina screening for diabetic retinopathy: recommendations from the Canadian Retina Research Network (CR2N) Tele-Retina Steering Committee.

OBJECTIVE: The purpose of this report is to develop a consensus for Canadian national guidelines specific to a tele-medicine approach to screening for diabetic retinopathy (DR) using evidence-based and clinical data. METHODS: Canadian Tele-Screening Grading Scales for DR and diabetic macular edema (DME) were created primarily based on severity grading scales outlined by the International Clinical Diabetic Retinopathy Disease Severity Scale (ICDR) and the Scottish DR Grading Scheme 2007. Other grading scales used in international screening programs and the clinical expertise of the Canadian Retina Research Network members and retina specialists nationwide were also used in the creation of the guidelines. RESULTS: National Tele-Screening Guidelines for DR and DME with and without optical coherence tomography (OCT) images are proposed. These outline a diagnosis and management algorithm for patients presenting with different stages of DR and/or DME. General guidelines detailing the requirements for imaged retina fields, image quality, quality control, and follow-up care and the role of visual acuity, pupil dilation, OCT, ultra-wide-field imaging, and artificial intelligence are discussed. CONCLUSIONS: Tele-retina screening can help to address the need for timely and effective screening for DR, whose prevalence continues to rise. A standardized and evidence-based national approach to DR tele-screening has been proposed, based on DR/DME grading using two 45° image fields or a single widefield or ultra-wide-field image, preferable use of OCT imaging, and a focus on local quality control measures.

Dissemination of non-typhoidal Salmonella during Plasmodium chabaudi infection affects anti-malarial immunity.

Malaria-associated bacteremia accounts for up to one-third of deaths from severe malaria, and non-typhoidal Salmonella (NTS) has been reported as a major complication of severe malarial infection. Patients who develop NTS bacteremia during Plasmodium infection show higher mortality rates than individuals with malaria alone. Systemic bacteremia can be caused by a wound or translocation from epithelial or endothelial sites. NTS is an intestinal pathogen, however the contribution of bacterial translocation from the intestinal tract during Plasmodium infection is not well studied. Here, we investigated the integrity of the intestinal barrier function of P. chabaudi-infected mice using large molecules and Salmonella infection. Intestinal histology and the adaptive immune response to malaria were also studied using light microscopy and flow cytometry. P. chabaudi infection compromised intestinal barrier function, which led to increased intestinal cellular infiltration. In addition, we observed increased serum lipopolysaccharide binding protein and leakage of soluble molecules from the intestine into the blood in infected mice. Plasmodium infection also increased intestinal translocation and dissemination of NTS to the liver. The adaptive immune response to P. chabaudi infection was also significantly impacted by NTS translocation. Reduced B and T cell activation were observed in co-infected animals, suggesting interference in the malaria-specific immune responses by bacteremia. These studies demonstrate that P. chabaudi infection induces failure of the barrier function of the intestinal wall and enhanced intestinal bacterial translocation, affecting anti-malarial immunity.