Assessment of proline function in higher plants under extreme temperatures.

Climate change and abiotic stress factors are key players in crop losses worldwide. Among which, extreme temperatures (heat and cold) disturb plant growth and development, reduce productivity and, in severe cases, lead to plant death. Plants have developed numerous strategies to mitigate the detrimental impact of temperature stress. Exposure to stress leads to the accumulation of various metabolites, e.g. sugars, sugar alcohols, organic acids and amino acids. Plants accumulate the amino acid 'proline' in response to several abiotic stresses, including temperature stress. Proline abundance may result from de novo synthesis, hydrolysis of proteins, reduced utilization or degradation. Proline also leads to stress tolerance by maintaining the osmotic balance (still controversial), cell turgidity and indirectly modulating metabolism of reactive oxygen species. Furthermore, the crosstalk of proline with other osmoprotectants and signalling molecules, e.g. glycine betaine, abscisic acid, nitric oxide, hydrogen sulfide, soluble sugars, helps to strengthen protective mechanisms in stressful environments. Development of less temperature-responsive cultivars can be achieved by manipulating the biosynthesis of proline through genetic engineering. This review presents an overview of plant responses to extreme temperatures and an outline of proline metabolism under such temperatures. The exogenous application of proline as a protective molecule under extreme temperatures is also presented. Proline crosstalk and interaction with other molecules is also discussed. Finally, the potential of genetic engineering of proline-related genes is explained to develop 'temperature-smart' plants. In short, exogenous application of proline and genetic engineering of proline genes promise ways forward for developing 'temperature-smart' future crop plants.

Association of HMGBP1 expression with clinical periimplant parameters among smokers and never-smokers with and without peri-implantitis.

OBJECTIVE: With our study we aimed at investigating the levels of high mobility group box chromosomal protein-1 (HMGB-1), tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-1ß in periimplant crevicular fluid (PICF) of smokers and never-smokers, with and without periimplantitis, and correlate these levels with the clinical and radiographic periimplant parameters. SUBJECTS AND METHODS: Sixty participants (n=15/group) were recruited and divided into 4 groups: cigarette smokers with periimplantitis (CSPI); cigarette smokers without periimplantitis (CSNPI); never-smokers with periimplantitis (NSPI); and never-smokers without periimplantitis (NSNPI). Clinical and radiographic periimplant parameters, including plaque scores (PS), bleeding on probing (BOP), probing depth (PD) and crestal bone level (CBL), were assessed. Crevicular levels of HMGB-1, TNF-α, and IL-1ß were quantified using human enzyme linked immunosorbent assay. p-values were generated using Kruskal-Wallis' test for comparison between the study groups, while correlations between HMGB-1, TNF-α, IL-1ß levels and clinical variables were analyzed using Spearman rank correlation coefficient analysis. RESULTS: Bleeding on probing was least in NSNPI and CSNPI followed by CSPI and NSPI (p<0.05). The highest PD and CBL was recorded for CSPI and NSPI groups, while the least PD and CBL were recorded among non-periimplantitis groups. HMGB-1 and IL-1ß were found to be significantly highest in CSPI groups followed by NSPI and CSNPI groups with no statistically significant difference between CSPI and NSPI groups (p<0.05). CSPI groups reported the highest TNF-α levels in the PICF in comparison to other groups (p<0.05). A significant negative correlation was observed between plaque scores (p=0.0187) and CBL (p=0.0049) in NSNPI and CSPI groups with HMGB-1, respectively. A significant positive correlation was seen for HMGB-1 in groups CSPI (p=0.0023) and NSPI (p=0.0018) for BOP. In CSPI group, a significant positive correlation was observed between TNF-α and PD (p=0.0443). On correlating IL-1ß, a significant positive correlation was observed for CBL in CSPI (p=0.0006) and NSPI (p=0.0275) groups, respectively. CONCLUSIONS: HMGB-1 could play a significant role in periimplant inflammatory response and inflammation. Higher crevicular fluid HMGB-1 levels are indicative of a possible surrogate biomarker for peri-implantitis.

Antioxidant Potential, DNA Damage, Inflammation, Glycemic Control and Lipid Metabolism Alteration: A Mediation Analysis of Islamic Sunnah Intermittent Fasting on Cognitive Function among Older Adults with Mild Cognitive Impairment.

OBJECTIVES: This study aimed to determine the relationship between oxidative stress, DNA damage, inflammation, and metabolic biomarkers as the mediating factor between Islamic Sunnah intermittent fasting (IF) practice and cognitive function among older adults with mild cognitive impairment (MCI). DESIGN: This study was a 36 months prospective cohort study. SETTING: Community-dwelling older participants recruited through a stratified random sampling method from four states representing Malaysia's central, north-west, northeast and southern regions. PARTICIPANTS: Ninety-nine Malay Muslim older adults (n= 99) aged 60 and above with MCI and no known critical illnesses were included in the current analysis. The participants were divided into regularly practicing IF (r-IF), irregularly practicing IF (i-IF) and not practicing IF (n-IF) groups. MEASUREMENTS: Fasting venous blood was collected and used to determine the levels of oxidative stress, DNA damage, inflammatory and metabolic biomarkers. Mini-Mental State Examination, Montreal Cognitive Assessment, Rey Auditory Verbal Learning Test, Digit Span and Digit symbol were used to evaluate the cognitive function. Then, the mediation analysis was conducted using a multistep regression model to determine the mediating role of various biomarkers between IF practice and cognitive function. RESULTS: When comparing the r-IF and n-IF groups, higher SOD activity, lower DNA damage (percentage of DNA in tail), lower CRP levels and higher HDL-cholesterol levels established partial mediation while lower insulin levels established complete mediation between IF practice and better cognitive function. Meanwhile, when comparing the r-IF and i-IF groups, higher SOD activity and lower CRP levels completely mediated the effects of IF practice on better cognitive function. CONCLUSION: It can be concluded that changes in antioxidant function, DNA damage, inflammation and a limited set of metabolic biomarkers (insulin and HDL cholesterol) may mediate improvements in cognitive function among older participants with MCI who practice Islamic Sunnah IF.

Peroneal Artery Adipofascial Flaps for Coverage of Distal Leg and Rearfoot.

Chronic wounds of the lower extremity can pose several obstacles for the treating physician as well as the patient. Peroneal artery adipofascial flaps have been shown to be a reliable and durable option for reconstruction of these defects for many reasons, including ease of dissection, minimized donor site mobility, reliability of take to underlying surfaces, and cosmetically more pleasing outcome. This article discusses the current literature regarding the use of peroneal artery adipofascial flaps and our surgical technique for harvest, transfer, and postoperative course for this versatile flap.

Diabetic keratopathy: Insights and challenges.

Ocular complications from diabetes mellitus are common. Diabetic keratopathy, the most frequent clinical condition affecting the human cornea, is a potentially sight-threatening condition caused mostly by epithelial disturbances that are of clinical and research attention because of their severity. Diabetic keratopathy exhibits several clinical manifestations, including persistent corneal epithelial erosion, superficial punctate keratopathy, delayed epithelial regeneration, and decreased corneal sensitivity, that may lead to compromised visual acuity or permanent vision loss. The limited amount of clinical studies makes it difficult to fully understand the pathobiology of diabetic keratopathy. Effective therapeutic approaches are elusive. We summarize the clinical manifestations of diabetic keratopathy and discuss available treatments and up-to-date research studies in an attempt to provide a thorough overview of the disorder.

DNA Damage, Copper and Lead Associates with Cognitive Function among Older Adults.

BACKGROUND: A cross sectional study was conducted in a group of 317 subjects older than 60 in Malaysia, aimed to determine risk factors associated with cognitive impairment in older adults, focusing on trace elements and DNA damage. METHOD: Cognitive decline was determined by Montreal Cognitive Assessment (MoCA). Oxidative stress markers (malondialdehyde-MDA and superoxide dismutase-SOD) were determined and DNA damage was assayed using Alkaline Comet Assay. Toenail samples were taken and analyzed using ICP-MS to determine trace element levels. RESULTS: A total of 62.1 % of subjects had cognitive impairment. Subjects with cognitive impairment had significantly higher levels of MDA and DNA damage as compared to the group with normal cognitive function; MDA (2.07 ± 0.05 nmol/L vs 1.85 ± 0.06 nmol/L) (p<0.05) and DNA damage (% Tail Density, 14.52 ± 0.32 vs 10.31 ± 0.42; Tail Moment, 1.79 ± 0.06 vs 1.28 ± 0.06) (p<0.05 for all parameters). However, the level of SOD among subjects with cognitive impairment (6.67 ± 0.33 u.e/min/mg protein) was lower than the level among those with normal cognitive functions (11.36 ± 0.65 u.e/min/mg protein) (p<0.05). Multiple logistic regression revealed the predictors for cognitive impairment among the subjects were DNA damage (Adjusted odd ratio [OR], 1.37; 95% confidence interval [CI], 1.18-1.59), level of trace elements in toenails namely, lead (OR, 2.471; CI, 1.535-3.980) and copper (OR, 1.275; CI, 1.047-1.552) (p<0.05). CONCLUSION: High levels of lead and copper can lead to increase in oxidative stress levels and are associated with DNA damage that eventually could be associated with cognitive decline.

Acute Gastric Volvulus in a 16-Year-Old Male Adolescent: A Case Report.

OBJECTIVE: We described a case of acute mesenteroaxial gastric volvulus in a male adolescent who presented to the pediatric emergency department (ED). CASE: A previously healthy male adolescent presented to the pediatric ED with gradual onset of epigastric pain, emesis, and a soft and nondistended abdomen. After evaluation, management, and resolution of the pain, the patient was discharged home with a primary care follow-up plan. Approximately 5 hours after discharge, the patient returned to the pediatric ED with worsening abdominal pain, the inability to tolerate oral intake, and a firm and distended abdomen. Subsequent evaluation identified an acute mesenteroaxial gastric volvulus. Pediatric surgeons performed an exploratory laparotomy, reduction of the gastric volvulus, and gastropexy, and the patient was discharged after a brief hospitalization. CONCLUSIONS: Acute gastric volvulus can present with symptoms similar to benign abdominal etiologies. Timely diagnosis and intervention are key to improved outcomes for patients.

Cognitive impairment, genomic instability and trace elements.

Cognitive impairments are often related to aging and micronutrient deficiencies. Various essential micronutrients in the diet are involved in age-altered biological functions such as, zinc, copper, iron, and selenium that play pivotal roles either in maintaining and reinforcing the antioxidant performances or in affecting the complex network of genes (nutrigenomic approach) involved in encoding proteins for biological functions. Genomic stability is one of the leading causes of cognitive decline and deficiencies or excess in trace elements are two of the factors relating to it. In this review, we report and discuss the role of micronutrients in cognitive impairment in relation to genomic stability in an aging population. Telomere integrity will also be discussed in relation to aging and cognitive impairment, as well as, the micronutrients related to these events. This review will provide an understanding on how these three aspects can relate with each other and why it is important to keep a homeostasis of micronutrients in relation to healthy aging. Micronutrient deficiencies and aging process can lead to genomic instability.

The overview of cancer patients attending in a specialized hospital: A cross sectional study.

According to National Institute of Cancer Research and Hospital most frequently observed cancers in Bangladeshi population are lungs, breast, cervix, lymph node, esophagus, larynx and stomach. The point of epidemiological background, the rate of incidence and mortality are likely unavailable due to lack of population based cancer registry system in Bangladesh. This cross-sectional study was conducted from 2003 to 2012 with an aim to describe trends and pattern of cancer cases attended a specialized hospital in Dhaka city. A total of 29,999 cancer cases was enrolled and among them the male and female ratio was 1.2:1. The study revealed that around half of the patients attended from Dhaka division, followed by Chittagong division (22.9%) and Sylhet division (8.8%). According to the organ involvement most frequently reported malignancies in males were lung cancer (24.2%), followed by eight percent larynx cancer and six percent lymph node cancer, whereas in females were breast cancer (27.5%), followed by cervix cancer (19.5%) and five percent lung cancer. It has been found that the system involvement was observed of cancers among male's respifatory system (33.5%) followed by the digestive organs (20.0%) and oral cavity (14.2%) whereas in females were reproductive organs (26.3%), followed by fourteen percent digestive organs and eight percent oral cancer. The overall cancer trend showed a gradual rise of cancer cases in both sexes. The rate was higher in females rather than male. Without the availability of population based registries, incidence and mortality figures; studies like the present one may provide useful leads for health planning and future exploration.

Impact of toll-like receptor 4 on the severity of acute pancreatitis and pancreatitis-associated lung injury in mice.

BACKGROUND AND AIMS: Acute pancreatitis is an inflammatory disease involving acinar cell injury, and the rapid production and release of inflammatory cytokines, which play a dominant role in local pancreatic inflammation and systemic complications. Toll-like receptor 4 (TLR4) initiates a complex signalling pathway when it interacts with lipopolysaccharide (LPS), which ultimately results in a proinflammatory response. We hypothesised that TLR4 is important in the pathophysiology of acute pancreatitis, independently of LPS. Using two different models of acute pancreatitis, we investigated how genetic deletion of TLR4 or its co-receptor CD14 effects its progression and severity. METHODS: We induced acute pancreatitis by administering either caerulein or L-arginine to wild-type, TLR4(-/-), and CD14(-/-) mice. Control mice received normal saline injections. The severity of acute pancreatitis was determined by measuring serum amylase activity, quantifying myeloperoxidase (MPO) activity in the pancreatic tissue, and histologically assessing acinar cell injury. RESULTS: It was found that administering caerulein and L-arginine to wild-type mice resulted in acute pancreatitis (as assessed by hyperamylasaemia, oedema, increased pancreatic MPO activity, and pancreatic necrosis) and associated lung injury. The same treatment to TLR4(-/-) or CD14(-/-) mice resulted in significantly less severe acute pancreatitis, and reduced lung injury. We found no evidence of either bacteria or LPS in the blood or in pancreatic tissue. CONCLUSIONS: The severity of acute pancreatitis is ameliorated in mice that lack either TLR4 or CD14 receptors. Furthermore, these results indicate that TLR4 plays a significant pro-inflammatory role independently of LPS in the progression of acute pancreatitis.

Stigma in the HIV/AIDS epidemic: a review of the literature and recommendations for the way forward.

Although stigma is considered a major barrier to effective responses to the HIV/AIDS epidemic, stigma reduction efforts are relegated to the bottom of AIDS programme priorities. The complexity of HIV/AIDS-related stigma is often cited as a primary reason for the limited response to this pervasive phenomenon. In this paper, we systematically review the scientific literature on HIV/AIDS-related stigma to document the current state of research, identify gaps in the available evidence and highlight promising strategies to address stigma. We focus on the following key challenges: defining, measuring and reducing HIV/AIDS-related stigma as well as assessing the impact of stigma on the effectiveness of HIV prevention and treatment programmes. Based on the literature, we conclude by offering a set of recommendations that may represent important next steps in a multifaceted response to stigma in the HIV/AIDS epidemic.

Toxicological evaluation of some Malaysian locally processed raw food products.

Malaysian locally processed raw food products are widely used as main ingredients in local cooking. Previous studies showed that these food products have a positive correlation with the incidence of cancer. The cytotoxicity effect was evaluated using MTT assay (3-(4,5-dimetil-2-thiazolil)-2,5-diphenyl-2H-tetrazolium bromide) against Chang liver cells at 2000 microg/ml following 72 h incubation. Findings showed all methanol extracts caused a tremendous drop in the percentage of cell viability at 2000 microg/ml (shrimp paste - 41.69+/-3.36%, salted fish - 37.2+/-1.06%, dried shrimp - 40.32+/-1.8%, p<0.05). To detect DNA damage in a single cell, alkaline Comet Assay was used. None of the extracts caused DNA damage to the Chang liver cells at 62.5 microg/ml following 24 h incubation, as compared to the positive control, hydrogen peroxide (tail moment - 9.50+/-1.50; tail intensity - 30.50+/-2.50). Proximate analysis which was used for the evaluation of macronutrients in food showed that shrimp paste did not comply with the protein requirement (<25%) as in Food Act 1983. Salt was found in every sample with the highest percentage being detected in shrimp paste which exceeded 20%. Following heavy metal analysis (arsenic, cadmium, lead and mercury), arsenic was found in every sample with dried shrimps showing the highest value as compared to the other samples (6.16 mg/kg). In conclusion, several food extracts showed cytotoxic effect but did not cause DNA damage against Chang liver cells. Salt was found as the main additive and arsenic was present in every sample, which could be the probable cause of the toxicity effects observed.

Proteolytic processing of dynamin by cytoplasmic cathepsin L is a mechanism for proteinuric kidney disease.

Kidney podocytes and their foot processes maintain the ultrafiltration barrier and prevent urinary protein loss (proteinuria). Here we show that the GTPase dynamin is essential for podocyte function. During proteinuric kidney disease, induction of cytoplasmic cathepsin L leads to cleavage of dynamin at an evolutionary conserved site, resulting in reorganization of the podocyte actin cytoskeleton and proteinuria. Dynamin mutants that lack the cathepsin L site, or render the cathepsin L site inaccessible through dynamin self-assembly, are resistant to cathepsin L cleavage. When delivered into mice, these mutants restored podocyte function and resolve proteinuria. Our study identifies dynamin as a critical regulator of renal permselectivity that is specifically targeted by proteolysis under pathological conditions.

Dynasore puts a new spin on dynamin: a surprising dual role during vesicle formation.

During clathrin-mediated endocytosis, dynamin promotes the formation of clathrin-coated vesicles, but its mode of action is unresolved. In a recent study, Macia and colleagues made use of dynasore, a dynamin-specific inhibitor, to show that dynamin plays a dual role in endocytosis: they confirmed that dynamin is involved in detaching fully formed coated pits from the membrane, and also propose a new role for dynamin earlier in the process at the point of invagination.

First case of bioterrorism-related inhalational anthrax in the United States, Palm Beach County, Florida, 2001.

On October 4, 2001, we confirmed the first bioterrorism-related anthrax case identified in the United States in a resident of Palm Beach County, Florida. Epidemiologic investigation indicated that exposure occurred at the workplace through intentionally contaminated mail. One additional case of inhalational anthrax was identified from the index patient's workplace. Among 1,076 nasal cultures performed to assess exposure, Bacillus anthracis was isolated from a co-worker later confirmed as being infected, as well as from an asymptomatic mail-handler in the same workplace. Environmental cultures for B. anthracis showed contamination at the workplace and six county postal facilities. Environmental and nasal swab cultures were useful epidemiologic tools that helped direct the investigation towards the infection source and transmission vehicle. We identified 1,114 persons at risk and offered antimicrobial prophylaxis.

The in vitro and ex vivo antioxidant properties, and hypolipidemic activity of CGP 2881.

This report describes the in vitro and ex vivo antioxidant properties of a new antioxidant, CGP 2881. This compound is structurally similar to probucol, in that both compounds contain bis-tertiary butyl phenyl groups. However, CGP 2881 consistently inhibited CuSO4 (Cu2+)- and macrophage (MO)-induced oxidation of human low density lipoproteins (LDL) more potently than equimolar concentrations of probucol. CGP 2881 (1 mumol/l) prolonged the lag phase of diene formation during Cu(2+)-induced LDL oxidation by 3.4 versus 1.5-fold prolongation with 1 mumol/l probucol (P < 0.05 vs CGP 2881). The IC50 for inhibiting the formation of Cu(2+)-induced thiobarbituric acid-reactive substances (TBARS) was 0.15 mumol/l for CGP 2881, versus approximately 10 mumol/l for probucol. The IC50 for MO-induced oxidation of LDL (TBARS) was 0.64 mumol/l. In contrast, 1 mumol/l probucol failed to inhibit MO-induced oxidation of LDL. Treatment of cholic acid/cholesterol-fed rats with CGP 2881 (50 mg/kg per day, orally for 5 days) inhibited ex vivo Cu(2+)-induced oxidation (TBARS) of the very low density lipoproteins (VLDL) + LDL lipoprotein fraction by 93% versus vehicle controls (P < 0.0001), and prolonged the lag phase for Cu(2+)-induced diene formation by 3.4-fold over vehicle-treated controls. Five days of orally administered CGP 2881 reduced plasma total cholesterol and LDL cholesterol levels to 55 and 54% of vehicle-treated controls, respectively (P < 0.05). In contrast, probucol had no appreciable effect on plasma total cholesterol or LDL cholesterol levels, unless administered for longer than 5 days. Treatment of hypercholesterolemic rabbits with 50 mg/kg per day orally for 5-12 days delayed the lag phase of diene formation during LDL oxidation by 4.3-fold over controls. However, the relative antioxidant potencies of CGP 2881 and probucol seen with oral administration to hypercholesterolemic rabbits were reversed when the compounds were given intravenously. In addition, the effects of these antioxidants were potentiated when given to normocholesterolemic rabbits compared to hypercholesterolemic animals. These data establish that CGP 2881 demonstrates hypolipidemic activity and is a substantially more potent antioxidant than probucol (in vitro and ex vivo). CGP 2881 may be useful as a new antioxidant tool in the effort to better understand the atherogenicity of oxidized LDL (oxLDL).

Demonstration of potent lipid-lowering activity by a thyromimetic agent devoid of cardiovascular and thermogenic effects.

A potent lipid-lowering thyromimetic (CGS 26214) devoid of cardiac and thermogenic activity was identified based on its ability to preferentially access and bind the nuclear fraction of hepatocytes over that of myocytes in culture. The difference in access achieved with CGS 26214 was at least 100-fold better for hepatocytes than for myocytes. This in vitro hepatoselectivity resulted in a compound with unprecedented in vivo lipid-lowering potency with a minimal effective dose of 1 microgram/kg in rats and dogs (approximately 25x that of L-T3). At the same time, CGS 26214 was free of any cardiovascular effects up to the highest dose tested of 25 mg/kg and 100 micrograms/kg in rats and dogs, respectively.