Epidemiology and demographic patterns of cardiovascular diseases and neoplasms deaths in Western Europe: a 1990-2019 analysis.

OBJECTIVES: Cardiovascular diseases (CVDs) and neoplasms have been considered as public health concerns worldwide. This study aimed to estimate the epidemiological patterns of death burden on CVDs and neoplasms and its attributable risk factors in Western Europe from 1990 to 2019 to discuss the potential causes of the disparities. STUDY DESIGN AND METHODS: We collected data on CVDs and neoplasms deaths in 24 Western European countries from the Global Burden of Disease Study. We analyzed patterns by age, sex, country, and associated risk factors. The results include percentages of total deaths, age-standardized death rates per 100,000 population, and uncertainty intervals (UIs). Time trends were assessed using annual percent change. RESULTS: In 2019, CVDs and neoplasms accounted for 33.54% and 30.15% of Western Europe's total deaths, with age-standardized death rates of 128.05 (95% UI: 135.37, 113.02) and 137.51 (95% UI: 142.54, 128.01) per 100,000. Over 1990-2019, CVDs rates decreased by 54.97%, and neoplasms rates decreased by 19.54%. Top CVDs subtypes were ischemic heart disease and stroke; top cancers for neoplasms were lung and colorectal. Highest CVD death burdens were in Finland, Greece, Austria; neoplasm burdens in Monaco, San Marino, Andorra. The major risk factors were metabolic (CVDs) and behavioral (neoplasms). Gender differences revealed higher CVDs death burden in males, while neoplasms burden varied by risk factors and age groups. CONCLUSION: In 2019, CVDs and neoplasms posed significant health risks in Western Europe, with variations in death burdens and risk factors across genders, age groups, and countries. Future interventions should target vulnerable groups to lessen the impact of CVDs and neoplasms in the region.

A two-generational reproductive study to assess the effects of Juglans regia on reproductive developments in the male and female rats.

Environmental pollutants and lifestyle severely threaten human and animal health, leading to disturbances of various functions, including infertility. So, exploring a safe treatment that could effectively reverse infertility remains a challenge. The current study was intended to explore the fertility-enhancing effect of Juglans Regia oil in two successive generations of rats; F0 and F1. J. Regia oil was initially tested for in vitro antioxidant assay via ROS and DPPH, followed by in vivo toxicity testing. In the fertility assessment, eighteen pairs of male and female rats (n=36, 1:1, F0 generation) were divided into three groups and dosed with 1 mL/kg and 2 mL/kg daily of J. Regia oil and saline, respectively, up to pre-cohabitation, cohabitation, gestation and lactation periods. The reproductive performance, including body weight, live birth index, fertility index, and litter size, was assessed. Hormonal and antioxidant markers of F1 generations were assessed with the histopathological evaluation of male and female organs. The oil of J. Regia showed great antioxidant potential (P < 0.05) in DPPH (1,1-diphenyl-2-picrylhydrazyl) and ROS (Reactive Oxygen Species) methods (P<0.05). The continued exposure of the F0 and F1 generations to J. Regia oil did not affect body weight, fertility index, litter size, and survival index. We have found pronounced fertility outcomes in both genders of F0 and F1 generations with J. Regia 2 mL/kg/day in comparison to the control. Results showed that J. Regia significantly increased (P < 0.05) luteinizing hormone (LH), plasma testosterone, follicular stimulating hormone (FSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities in both generations. Histology of both generations reveals improved spermatogenesis and folliculogenesis with enhanced architecture. Altogether, the present results suggest that J. Regia improved fertility in both male and female rats by improving hormonal activities and oxidative stress.

Effect of dapagliflozin against NAFLD and dyslipidemia in type 2 diabetic albino rats: possible underlying mechanisms.

OBJECTIVE: The aim was to investigate the effect of dapagliflozin on non-alcoholic fatty liver disease and dyslipidemia in type 2 diabetic rats by studying the histopathological structure of the liver and detecting possible underlying mechanisms for this impact by evaluating the potential anti-inflammatory action of dapagliflozin. MATERIALS AND METHODS: 100 albino rats were used in this work and divided into five equal groups: group I (Control group), group II (Control diabetic group), group III (was administered dapagliflozin, 0.75 mg/kg, p.o.), group IV (was administered dapagliflozin, 1.5 mg/kg, p.o.), and group V (was administered dapagliflozin, 3 mg/kg, p.o.). RESULTS: In our study, the total body weight, liver weight, liver index, blood glucose level, insulin level, insulin resistance, total cholesterol, triglycerides, liver enzymes, IL-1 ß, and MDA were significantly higher in the control diabetic group than the normal group. The dapagliflozin reduced all the above variables significantly in a dose-dependent manner compared to the control diabetic group (p-value = 0.001 for all). CONCLUSIONS: Dapagliflozin may be a promising novel treatment strategy for treating T2DM-related non-alcoholic fatty liver disease (NAFLD), and dyslipidemia where it possesses anti-oxidative, anti-inflammatory and anti-dyslipidemic effects.

Analysis of phase stability, elastic, electronic, thermal, and optical properties of Sc1-xYxN via ab initio methods.

Understanding the physical properties of a material is crucial to know its applicability for practical applications. In this study, we investigate the phase stability, elastic, electronic, thermal, and optical properties of the ternary alloying of the scandium and yttrium nitrides (Sc1-xYxN) for different compositions. To do so, we apply a "density functional theory (DFT)" based scheme of calculations named as "full potential (FP) linearized (L) augmented plane wave plus local orbitals (APW + lo) method" realized in the WIEN2k computational package. At first, the phase stability of the investigated compositions of the mentioned alloy is determined. The analysis of our calculations shows that Sc1-xYxN alloy is stable in rock salt crystal structure for all investigated compositions. Next to that, the elastic properties of the rock-salt phase of the studied ternary alloy Sc1-xYxN at all above said compositions were done at the level of "Wu-Cohen generalized gradient approximation (Wu-GGA)" within DFT. However, Trans-Blaha (TB) approximation of the "modified Becke-Johson (mBJ)" potential is also used in combination with Wu-GGA where the thermal properties are calculated at the level of the "quasi-harmonic Debye model." The obtained results for the absorption coefficients, and optical bandgap, represent that the title alloy may be a suitable candidate for the applications in optoelectronic devices.

Occult tension pneumothorax discovered following imaging for adult trauma patients in the modern major trauma system: a multicentre observational study.

BACKGROUND: Tension pneumothorax following trauma is a life-threatening emergency and radiological investigation is normally discouraged prior to treatment in traditional trauma doctrines such as ATLS. Some trauma patients may be physiologically stable enough for diagnostic imaging and occult tension pneumothorax is discovered radiologically. We assessed the outcomes of these patients and compared them with those with clinical diagnosis of tension pneumothorax prior to imaging. METHODS: A multicentre civilian-military collaborative network of six major trauma centres in the UK collected observational data from adult patients who had a diagnosis of traumatic tension pneumothorax during a 33-month period. Patients were divided into 'radiological' (diagnosis following CT/CXR) or 'clinical' (no prior CT/CXR) groups. The effect of radiological diagnosis on survival was analysed using multivariable logistic regression that included the covariates of age, gender, comorbidities and Injury Severity Score. RESULTS: There were 133 patients, with a median age of 41 (IQR 24-61); 108 (81%) were male. Survivors included 49 of 59 (83%) in the radiological group and 59 of 74 (80%) in the clinical group (p=0.487). Multivariable logistic regression showed no significant association between radiological diagnosis and survival (OR 2.40, 95% CI 0.80 to 7.95; p=0.130). There was no significant difference in mortality between the groups. CONCLUSION: Radiological imaging may be appropriate for selected trauma patients at risk of tension pneumothorax if they are considered haemodynamically stable. Trauma patients may be physiologically stable enough for radiological imaging but have occult tension pneumothorax because they did not have the typical clinical presentation. The historical dogma of the 'forbidden scan' no longer applies to such patients.

Cytotoxic Effects of Phytomediated Silver and Gold Nanoparticles Synthesised from Rooibos (Aspalathus linearis), and Aspalathin.

The green chemistry approach has continuously been applied for the synthesis of functional nanomaterials to reduce waste, environmental hazards, and the use of toxic chemicals among other reasons. Bioactive natural compounds have been found great potential in this regard and are used to improve the stability, activity, and biodistribution of metal nanoparticles (MNPs). Aspalathin (ASP) from Aspalathus linearis (rooibos) has a well-defined pharmacological profile and functional groups capable of both reducing and capping agents in the synthesis of metallic nanoparticles (NP). This study provides the first report of the phytomediated synthesis of gold and silver nanoparticles (AuNPs/AgNPs) via ASP and the green rooibos (GR) extract. The study demonstrated a green chemistry approach to the biosynthesis of nanoparticles of GR-AuNPs, ASP-AuNPs, GR-AgNPs, and ASP-AgNPs. The results showed that GR and ASP could act both as reducing and stabilising agents in the formation of crystalline, with different shapes and dispersity of NPs in the ranges of 1.6-6.7 nm for AgNPs and 7.5-12.5 nm for the AuNPs. However, the ASP NPs were less stable in selected biogenic media compared to GR NPs and were later stabilised with polyethene glycol. The cytotoxicity studies showed that GR-AgNPs were the most cytotoxic against SH-SY5Y and HepG2 with IC50 108.8 and 183.4 µg/mL, respectively. The cellular uptake analysis showed a high uptake of AuNPs and indicated that AgNPs of rooibos at a lower dose (1.3-1.5 µg/mL) is favourable for its anticancer potential. This study is a contribution to plant-mediated metallic nanoparticles using a pure single compound that can be further developed for targeted drug delivery for cancer cells treatments in the coming years.

Protective Effects of Linearthin and Other Chalcone Derivatives from Aspalathus linearis (Rooibos) against UVB Induced Oxidative Stress and Toxicity in Human Skin Cells.

Skin cells suffer continuous damage from chronic exposure to ultraviolet light (UV) that may result in UV-induced oxidative stress and skin thinning. This has necessitated the formulation of cosmeceutical products rich in natural antioxidants and free radical scavengers. Aspalathus linearis (rooibos) is an endemic South African fynbos plant growing naturally in the Western Cape region. The plant is rich in phenolics and other bioactives with a wide spectrum of health benefits. The chemical study of an acetonic extract of green A. linearis afforded a novel compound named linearthin (1) and two known dihydrochalcones, aspalathin (2) and nothofagin (3). The chemical structure of the novel compound was elucidated based on spectroscopic data analysis. The bio-evaluation of the isolated chalcones in vitro for protection against UVB-induced oxidative stress were systematically assessed by examining cell viability, metabolic activity, apoptosis, and cytotoxicity using HaCaT and SK-MEL-1 skin cells models. It was observed that pre-treatment with tested samples for 4- and 24 h at low concentrations were sufficient to protect skin cells from UVB-induced damage in vitro as evidenced by higher cell viability and improved metabolic activity in both keratinocytes (HaCaT) and melanocytes (SK-MEL-1). The results further show that the pre-treatment regimen employed by this study involved some degree of cellular adaptation as evidenced by higher levels of reduced glutathione with a concomitant decrease in lipid peroxidation and lowered caspase 3 activity. Furthermore, compound 1 was most cytoprotective against UVB irradiation of HaCaT cell line (over 24 h) with an IC50 of 282 µg/mL and SK-MEL-1 cell line with IC50 values of 248.3 and 142.6 µg/mL over 4 and 24 h, respectively. On the other hand, HaCaT cells exposed to 2 over 4 h before UVB irradiation showed the highest degree of cytoprotection with an IC50 of 398.9 µg/mL among the four studied samples. These results show that linearthin (1) and the two glycoside dihydrochalcone of A. linearis have the potential to be further developed as antioxidant cosmeceutical ingredients that may protect skin against UVB-induced damage.

Indoor air quality and its relationship with cluster type in urban Pakistani households.

OBJECTIVE: To assess the levels and predictors of formaldehyde, nitrogen dioxide (NO2), carbon monoxide (CO) and fine particulate matter with diameter less than 2.5 µm (PM2.5) in Karachi, Pakistan.METHODS: A total of 1629 households were selected through multistage cluster sampling in a community-based cross-sectional survey. Formaldehyde, NO2 and CO levels were measured using YesAir Indoor air monitor and for PM2.5, UCB-PATS (University of California Berkeley Particle and Temperature Sensor) was used. Clusters were classified either as planned (areas of planned housing) or unplanned (informal settlements).RESULTS: We found the median concentrations to be as follows: formaldehyde, 0.03 ppm (IQR 0.00-0.090); CO, 0.00 ppm (IQR 0.00-1.00); NO2, 0 ppm (IQR 0.00-0.00) and PM2.5, 0.278 mg/m³ (IQR 0.162-0.526). We found a significant association of the upper quartiles of formaldehyde and PM2.5 levels with type of cluster. The risk of obtaining formaldehyde and PM2.5 levels in the upper quartile was higher in unplanned clusters than in planned clusters (adjusted odds ratio [aOR] 33.0, 95% CI 4.02-271.5 and aOR 0.10, 95% CI 0.001-0.16, respectively). No significant association was observed between levels of CO and cluster type (aOR 0.84, 95%CI 0.62-1.14).CONCLUSION: This study reports high levels of indoor air pollutants in Karachi, with considerable variation across planned vs. unplanned clusters.

MiR-146a G/C rs2910164 variation in South African Indian and Caucasian patients with psoriatic arthritis.

BACKGROUND: Psoriasis and psoriatic arthritis (PsA) are inflammatory associated autoimmune disorders. MicroRNA (miR)-146a plays a crucial role in regulating inflammation. A single nucleotide polymorphism in the miR-146a gene (rs2910164), aberrantly alters its gene expression and linked with the pathogenesis of several disorders, including psoriasis and PsA. In South Africa, psoriasis and PsA are extremely rare in the indigenous African population and most common in both the Indian and Caucasian population. The aim of this study was to investigate whether the miR-146a rs2910164 contributes towards psoriasis and PsA development in South African Indian and Caucasian patients. METHODS: South African Indian (n = 84) and Caucasian (n = 32) PsA patients (total n = 116) and healthy control subjects (Indian: n = 62 and Caucasian: n = 38; total n = 100) were recruited in the study. DNA was extracted from whole blood taken from all subjects, and genotyped for the miR-146a rs2910164 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Data for laboratory parameters were obtained from pathology reports. The consulting rheumatologist collected all other clinical data. RESULTS: Unstratified data (Caucasians + Indians): A significant decrease in C-reactive protein (CRP) levels in PsA patients was observed (CRP monitored at inclusion vs. after 6 months of treatment) (18.95 ± 2.81 mg/L vs. 9.68 ± 1.32 mg/L, p = 0.0011). The miR-146a rs2910164 variant C-allele frequency in PsA patients was significantly higher vs. healthy controls (35.78% vs. 26% respectively, p = 0.0295, OR = 1.59 95% CI 1.05-2.40). Stratified data (Indians): The variant C-allele frequency in Indian PsA patients was significantly higher vs. healthy Indian controls (35.71% vs. 22.58%, p = 0.0200, OR = 1.91 95% CI 1.13-3.22). Stratified data (Caucasians): The variant C-allele frequency distribution between Caucasian PsA patients and healthy Caucasian controls was similar. CONCLUSION: The rs2910164 variant C-allele may play a role in the progression of PsA in the South African Indian population. The main limitation in this study was the small sample size in the case-control cohorts, with a low overall statistical power (post-hoc power analysis = 19%).

Significance of immunohistochemical overexpression of cyclooxygenase-2 in overall and disease-free survival of oral squamous cell carcinoma patients.

OBJECTIVE: In Pakistan, oral cancer ranks as the most common malignancy in males and the second most common malignancy in females. Cyclooxygenase-2 has been explored as an agent of carcinogenesis in oral and other neoplasms. This study aimed to observe the expression of cyclooxygenase-2 in oral squamous cell carcinoma, and to correlate the expression with patients' clinical features and overall and disease-free survival. METHODS: Immunohistochemistry for cyclooxygenase-2 was performed on a total of 100 oral squamous cell carcinoma formalin-fixed, paraffin-embedded blocks. Expression was correlated with patients' clinicopathological variables and overall and disease-free survival. RESULTS: Cyclooxygenase-2 was overexpressed in 55 per cent of oral squamous cell carcinoma patients. Overexpression was correlated with overall survival (p = 0.013) and disease-free survival (p = 0.001) on univariate analysis. However, on multivariate analysis, cyclooxygenase-2 was associated with only disease-free survival (p = 0.044) and not overall survival (p = 0.208). CONCLUSION: Expression of cyclooxygenase-2 is associated with poorer overall survival and higher rates of recurrence in oral squamous cell carcinoma patients.

Motor cortex and spinal cord neuromodulation promote corticospinal tract axonal outgrowth and motor recovery after cervical contusion spinal cord injury.

Cervical injuries are the most common form of SCI. In this study, we used a neuromodulatory approach to promote skilled movement recovery and repair of the corticospinal tract (CST) after a moderately severe C4 midline contusion in adult rats. We used bilateral epidural intermittent theta burst (iTBS) electrical stimulation of motor cortex to promote CST axonal sprouting and cathodal trans-spinal direct current stimulation (tsDCS) to enhance spinal cord activation to motor cortex stimulation after injury. We used Finite Element Method (FEM) modeling to direct tsDCS to the cervical enlargement. Combined iTBS-tsDCS was delivered for 30min daily for 10days. We compared the effect of stimulation on performance in the horizontal ladder and the Irvine Beattie and Bresnahan forepaw manipulation tasks and CST axonal sprouting in injury-only and injury+stimulation animals. The contusion eliminated the dorsal CST in all animals. tsDCS significantly enhanced motor cortex evoked responses after C4 injury. Using this combined spinal-M1 neuromodulatory approach, we found significant recovery of skilled locomotion and forepaw manipulation skills compared with injury-only controls. The spared CST axons caudal to the lesion in both animal groups derived mostly from lateral CST axons that populated the contralateral intermediate zone. Stimulation enhanced injury-dependent CST axonal outgrowth below and above the level of the injury. This dual neuromodulatory approach produced partial recovery of skilled motor behaviors that normally require integration of posture, upper limb sensory information, and intent for performance. We propose that the motor systems use these new CST projections to control movements better after injury.

Biodiversity as a multidimensional construct: a review, framework and case study of herbivory's impact on plant biodiversity.

Biodiversity is inherently multidimensional, encompassing taxonomic, functional, phylogenetic, genetic, landscape and many other elements of variability of life on the Earth. However, this fundamental principle of multidimensionality is rarely applied in research aimed at understanding biodiversity's value to ecosystem functions and the services they provide. This oversight means that our current understanding of the ecological and environmental consequences of biodiversity loss is limited primarily to what unidimensional studies have revealed. To address this issue, we review the literature, develop a conceptual framework for multidimensional biodiversity research based on this review and provide a case study to explore the framework. Our case study specifically examines how herbivory by whitetail deer (Odocoileus virginianus) alters the multidimensional influence of biodiversity on understory plant cover at Black Rock Forest, New York. Using three biodiversity dimensions (taxonomic, functional and phylogenetic diversity) to explore our framework, we found that herbivory alters biodiversity's multidimensional influence on plant cover; an effect not observable through a unidimensional approach. Although our review, framework and case study illustrate the advantages of multidimensional over unidimensional approaches, they also illustrate the statistical and empirical challenges such work entails. Meeting these challenges, however, where data and resources permit, will be important if we are to better understand and manage the consequences we face as biodiversity continues to decline in the foreseeable future.

An assessment of adherence to basic ecological principles by payments for ecosystem service projects.

Programs and projects employing payments for ecosystem service (PES) interventions achieve their objectives by linking buyers and sellers of ecosystem services. Although PES projects are popular conservation and development interventions, little is known about their adherence to basic ecological principles. We conducted a quantitative assessment of the degree to which a global set of PES projects adhered to four ecological principles that are basic scientific considerations for any project focused on ecosystem management: collection of baseline data, identification of threats to an ecosystem service, monitoring, and attention to ecosystem dynamics or the formation of an adaptive management plan. We evaluated 118 PES projects in three markets-biodiversity, carbon, and water-compiled using websites of major conservation organizations; ecology, economic, and climate-change databases; and three scholarly databases (ISI Web of Knowledge, Web of Science, and Google Scholar). To assess adherence to ecological principles, we constructed two scientific indices (one additive [ASI] and one multiplicative [MSI]) based on our four ecological criteria and analyzed index scores by relevant project characteristics (e.g., sector, buyer, seller). Carbon-sector projects had higher ASI values (P < 0.05) than water-sector projects and marginally higher ASI scores (P < 0.1) than biodiversity-sector projects, demonstrating their greater adherence to ecological principles. Projects financed by public-private partnerships had significantly higher ASI values than projects financed by governments (P < 0.05) and marginally higher ASI values than those funded by private entities (P < 0.1). We did not detect differences in adherence to ecological principles based on the inclusion of cobenefits, the spatial extent of a project, or the size of a project's budget. These findings suggest, at this critical phase in the rapid growth of PES projects, that fundamental ecological principles should be considered more carefully in PES project design and implementation in an effort to ensure PES project viability and sustainability.

Culturable microbiota of ranched southern bluefin tuna (Thunnus maccoyii Castelnau).

AIMS: The Australian tuna industry is based on the ranching of wild southern bluefin tuna (SBT, Thunnus maccoyii). Within this industry, only opportunistic pathogens have been reported infecting external wounds of fish. This study aimed to identify different culturable bacteria present in three cohorts of SBT and to determine normal bacteria and potential pathogens in isolates from harvest fish and moribund/dead fish. Post-mortem changes in the microbiota were also studied. METHODS AND RESULTS: Moribund/dead showed a greater proportion of members from the family Vibrionaceae than harvested fish; the latter presented mainly non-Vibrio species. In harvested fish spleens, Vibrio splendidus I complex was the most commonly identified group among Vibrio isolates, while most groups from the family Vibrionaceae were isolated from gills. For moribund/dead, Vibrio chagasii and Photobacterium damselae subsp. damselae were common in gill, spleen and kidney samples. Non-Vibrio isolates from gills were characterized using 16S rRNA sequencing as Flavobacteriaceae and classes Gammaproteobacteria and Alphaproteobacteria, mainly from the genera Winogradskyella and Tenacibaculum. Post-mortem changes showed dynamic shifts in bacterial dominance in gills, with Vibrionaceae and non-Vibrio spp. found in similar proportions initially and types related to Pseudoalteromonas ruthenica prevailing after 27 h. Spleen samples showed little bacterial growth until 5 h post-mortem, while various Vibrio-associated species were isolated 27 h post-mortem. CONCLUSIONS: Bacterial isolates found include a range of potentially pathogenic bacteria that should be monitored though most of them have yet to be associated with disease in tuna. SIGNIFICANCE AND IMPACT OF THE STUDY: This study forms a foundation for future research into the bacterial population dynamics under different culture conditions of SBT. An understanding of the bacterial compositions in SBT is necessary to evaluate the effects of some bacterial species on their health.

A comparative analysis of toluidine blue with frozen section in oral squamous cell carcinoma.

BACKGROUND: Surgical excision of the primary tumor with safe margins remains the mainstay of treatment for oral cavity squamous cell carcinoma (OSCC). The standard of care for assessment of intraoperative margins is frozen section histopathology. Unfortunately the facility is not available at most centers in limited resource countries. Toluidine blue, a metachromatic dye, has been well described in clinical identification of malignant and premalignant lesion in the oral cavity. Considering this we decided to explore intraoperative use of toluidine blue staining, in comparison with frozen sections, for the assessment of tumor-free margins. METHODS: After obtaining clearance from the in-house ethical review committee, a prospective study was conducted at Aga Khan University Hospital, Karachi, from August 15, 2009 to March 14, 2010. A sample of 56 consenting patients with biopsy-proven OSCC were included in the study, giving us 280 tumor margins. Margins were analyzed using toluidine blue staining and frozen section histopathology. A receiver operator curve (ROC) was then applied to compare assessment of margin status by toluidine blue and frozen section. RESULTS: Of the 280 examined margins 11 stained positive with toluidine blue, three were positive on frozen section biopsy, and three were positive on final histopathology. Toluidine blue staining had sensitivity and specificity of 100% and 97%, respectively. The diagnostic accuracy of toluidine blue was found to be 97.1% with a positive predictive value (PPV) of 27.2% and a negative predictive value (NPV) of 100%. CONCLUSIONS: Toluidine blue can be used as an effective screening modality for the assessment of intraoperative margins in resource limited environments and reducing the number of frozen section biopsies performed. Further by providing real-time clinical information within minutes it can reduce indirect costs such as operating room time. It may also be used as an ad hoc for frozen section biopsies where frozen section facilities are available.

Helicobacter pylori: association with gall bladder disorders in Pakistan.

Helicobacter species colonise the biliary tract and therefore this study explores the relationship between of Helicobacter pylori and cholecystitis. Bile and gall bladder tissue samples were obtained from 144 patients who underwent cholecystectomy. Of these, 89 had chronic cholecystitis with cholelithiasis, 44 had gall bladder carcinoma and 11 had gall bladder polyps. Histopathology examination included special staining and immunohistochemistry (IHC), while Helicobacter species (H. pylori, H. bilis and H. hepaticus) were detected by the polymerase chain reaction (PCR). Sequencing and BLAST query of PCR products was undertaken and samples were considered to contain H. pylori if both PCR and IHC were positive. Immunohistochemistry for H. pylori was positive in 22 (25%) cases compared to five (9%) in the control group (P=0.02). Testing (PCR) for 16S rDNA was positive in 23 (26%) cases compared to six (11%) controls (P=0.03). Negative PCR results were obtained for H. bilis and H. hepaticus. Twenty-four (89%) were positive by both 16S rDNA PCR and IHC for H. pylori (P<0.001). Both PCR for 16S rDNA and IHC were positive in 21 (24%) cases compared to five (9%) controls (P=0.03). Sequencing of 16S rRNA and glmM PCR products were consistent with H. pylori. In conclusion, H. pylori DNA was demonstrated in cases of chronic cholecystitis and gall bladder carcinoma associated with cholelithiasis, but this association requires further study.

Transition states and origins of 1,4-asymmetric induction in alkylations of 2,2,6-trialkylpiperidine enamines.

The asymmetric C-alkylation of chiral enamines derived from terminal epoxides and lithium 2,2,6-trialkylpiperidides has previously been shown to provide alpha-alkylated aldehydes by intermolecular nucleophilic substitution in good levels of asymmetric induction. We now report a computational study of the origins of asymmetric induction in these reactions. Computational modeling with density functional theory (B3LYP/6-31G(d)) agrees closely with the experimental observations. This stereoselectivity is attributed to a preferential conformation of the enamine and the piperidine ring that places the C-6 alkyl substituent in an axial position due to A(1, 3) strain. Preferential attack occurs away from the axial group, for steric reasons. The effects of changing the C-6 substituent from methyl to isopropyl were studied, and twist transition states were found to contribute significantly in the latter alkylations.