Synthetic Routes to a Library of Novel Methionine Synthase Inhibitors

Fungal infections are of continuous concern, especially with regard to immunocompromised patients. In an effort to develop new potential anti-fungal agents, we have begun synthesizing a library of potential inhibitors of the fungal Methionine Synthase (MetSyn) enzyme. Key differences between the B12-independant fungal MetSyn enzyme and the B12-dependant mammalian form can allow for an antifungal drug to be developed to exclusively bind the fungal enzyme and inhibit fungal growth while leaving the host (patient) unaffected. We are currently exploring the synthesis of various pterin and deazaguanine-based molecules as these mimic folate, an essential substrate for MetSyn function. We have begun testing these new molecules for activity in a fungal growth assay, as well as a fluorescent assay for monitoring MetSyn activity

Comment on ‘Tumour-infiltrating inflammation and prognosis in colorectal cancer: systematic review and meta-analysis’

No abstract available

TAXES AND THE FEDERAL BUDGET: PROBLEMS AND ALTERNATIVES

Public Economics,

Resposta androgênica de genótipos brasileiros de trigo a diferentes pré-tratamentos das espigas e a um agente gelificante

The objective of this work was to analyze the androgenic response of Brazilian wheat genotypes to different pretreatments of the spikes, prior to the culture of isolated microspores, and to the effect of a gelling agent in the induction culture medium. Five genotypes were evaluated for embryo formation, green plantregeneration, and spontaneous chromosome duplication. Wheat spikes were subjected to two pretreatments:cold, at 4°C for 21 days; and 2-hydroxynicotinic acid, at 32°C for two days. Culture media were evaluated with or without Ficoll as a gelling agent. Cold produced more embryos and green plants than the chemical pretreatment in four out of five genotypes. Only two genotypes treated with 2-hydroxynicotinic acid were able to produce plants, and one of them produced a single albino plant. Medium containing Ficoll produced moreembryos than liquid medium and promoted a higher number of plants. Spontaneous chromosome duplication varies between genotypes and pretreatments, and shows high variability.O objetivo deste trabalho foi analisar a resposta androgênica de genótipos brasileiros de trigo a diferentes pré-tratamentos das espigas, antes da cultura de micrósporos isolados, e ao efeito de um agente gelificante no meio de cultura de indução. Cinco genótipos foram avaliados quanto à formação de embriões, regeneração de plantas verdes e à duplicação espontânea dos cromossomos. Espigas de trigo foram submetidas a dois pré-tratamentos: frio, a 4°C por 21 dias; e ácido 2-hidroxinicotínico, a 32°C por dois dias. Os meios decultura foram avaliados com ou sem Ficoll como agente gelificante. O frio produziu mais embriões e plantas verdes do que o pré-tratamento químico, em quatro dos cinco genótipos testados. Apenas dois genótipos tratados com ácido 2-hidroxinicotínico foram capazes de produzir plantas, e um deles produziu uma única planta albina. O meio com Ficoll produziu mais embriões do que o meio líquido e gerou maior número de plantas. A duplicação espontânea dos cromossomos varia entre os genótipos e os pré-tratamentos e apresentaalta variabilidade

Maternal exposure to carbon monoxide in the first trimester (7-13+6 weeks) of pregnancy in the core Niger Delta

Background: Irrespective of the fact that the Niger Delta was known for its environmental pollution, neither organized environmental assessment nor human biomonitoring, including that of carbon monoxide (CO) had been performed in the region. The aim of the study therefore was to establish the severity of maternal impact on exposure to CO in the first trimester of pregnancy by quantifying the exhaled CO concentrations (ECOC) and to assess the effect of maternal age, body mass index (BMI) and parity on the severity of the impact.Methods: The study was of cross-sectional design carried out at the Rivers State University Teaching Hospital (RSUTH) in Rivers State. 490 consecutive pregnant women in the first trimester were recruited from the antenatal clinic from January 2021 to January 2022. Gestational age was estimated with the aid of ultrasound scan. Demographic, social and obstetric characteristics were taken. Exhaled carbon monoxide concentration (ECOC) was measured with the aid of a smokerlyzer. Data was analyzed, using the statistical package for social sciences (SPSS) version 25.0 (Armonk, NY) software. Ethical approval was obtained from the RSUTH ethics committee.Results: The mean value of ECOC 3.25±2.51 ppm was more than that obtained in other studies. Out of the total 490 patients that were assessed, 335 (68.37%) had mild impact from CO exposure (ECOC=1-3 ppm), 129 (26.33%) – moderate impact (ECOC=4-6 ppm) and 26 (5.31%) had severe impact (ECOC=more than 6 ppm). Moderate and severe impacts were more prominent in women of age groups 25-39 years and the differences in various age groups were statistically significant [X2=20.671, p<0.036, 95% CI (0.032, 0.040)]. Patients with higher BMI were more likely to have moderate and severe impact than those with lower BMI- 6 (33.33%) and 4 (22.22%) out of the 18 patients with class III obesity had moderate and severe impacts respectively. The differences in the impact at various BMI were statistically significant [X2=20.671, p<0.001, 95% CI (0.001, 0.002)]. There was inverse relationship between parity and the severity of the impact and the differences in various parity groups were statistically significant [X2=10.580, p<0.012, 95% CI (0.101, 0.113)]. There was also a paradoxical finding of 3 smokers having only mild impact.Conclusions: The mean value of ECOC 3.25±2.51 ppm was more than that obtained in other studies in non-pregnant women. Mild, moderate and severe impact from maternal CO exposure were established with the moderate and severe impact more prominent at maternal ages of 25-39 years, at higher BMI and at lower parity

Factors related to the death of diabetic patients with COVID-19 hospitalized in Joseph Raseta Befelatanana University Hospital in Antananarivo, Madagascar

Background: Diabetes mellitus is associated with severe and even fatal forms of COVID-19. The objective of this study was to identify the factors linked to the death of COVID-19 diabetic patients in order to improve their care.Methods: An analytical cross-sectional study was carried out in the endocrinology department of the Joseph Raseta Befelatanana University Hospital Center, Antananarivo, Madagascar. It has concerned all the cases of COVID-19 diabetics (162 patients) recorded from April 2020 to July 2021 (16 months).Results: In our study, the case fatality rate of COVID-19 in diabetics was 14.49%. Significant factors related to death, after univariate analysis, were:  vascular complications including nephropathy (OR=4.74), neuropathy  (OR=5.38) and ischemic heart disease (OR=3.9), presence of other comorbidities (OR=9.02), dyspnea (OR=4.60), seizures (OR=6.22) or alertness disorder (OR=4.35), lower oxygen saturation (p=0.04), pleurisy (OR=4.67), signs of cardiac decompensation (OR=3.46), an elevated mean blood sugar level (p<0.001), leukocytosis (p=0.02) and thrombocytopenia (p<0.001), impaired renal function (p=0.02) and pleurisy on chest imaging (OR=5.29).Conclusions: Death factors in diabetics with COVID-19 can be diverse. They do not only include the cardiovascular complications of the diabetes, but also a worse clinical respiratory presentation on the admission, a higher inflammatory syndrome, and a greater imbalance of blood sugar during the hospitalization.

SOSIALISASI DAN PENDATAAN JENIS GOLONGAN DARAH BAGI KADER DAN TOKOH MASYARAKAT DALAM ACARA GERAKAN MASYARAKAT HIDUP SEHAT

Abstrak: Jenis golongan darah pada setiap orang sangat penting untuk diketahui. Individu yang satu dengan individu yang lainnya akan berbeda-beda, bahkan bisa sama, tergantung dari jenis antigen yang terdapat pada permukaan sel darah merah. Kader kesehatan di wilayah kerja Puskesmas Kahuripan sangat berperan aktif terutama dalam membantu masyarakat yang sangat membutuhkan donor darah. Namun, pencarian pendonor masih sering terkendala karena tidak tersedianya data jenis golongan darah ABO. Dengan mengetahui jenis golongan darah pada setiap kader diharapkan dapat membantu masyarakat secara langsung jika ada yang membutuhkan. Pengabdian ini bertujuan untuk mengidentifikasi atau mendata jenis golongan darah kader di wilayah kerja Puskesmas Mangkubumi Kota Tasikmalaya. Pelaksanaan pengabdian masyarakat dilakukan melalui sosialisasi dan pendataan dengan melakukan pemeriksaan setiap kader dalam suatu acara Germas. Peserta yang melakukan pemeriksaan jenis golongan darah ABO adalah sebanyak 32 orang (78%) dari total 41 orang.  Hasil yang telah dicapai dalam mengetahui jenis golongan darah ABO ini adalah jumlah data base jenis golongan darah A sebanyak 7 orang (22%), B sebanyak 7 orang (22%), AB sebanyak 3 orang (9%) dan O sebanyak 15 orang (47%). Abstract:  The type of blood group in each person is very important to know. Individuals from one individual to another will be different, even the same, depending on the type of antigen found on the surface of red blood cells. Health cadres in the working area of the Kahuripan Health Center play an active role, especially in helping people who really need blood donors. However, the search for donors is still often hampered due to the unavailability of data on the type of ABO blood type. By knowing the type of blood group in each cadre, it is hoped that it can help the community directly if someone needs it. This service aims to identify or record the type of blood group of cadres in the working area of the Mangkubumi Health Center, Tasikmalaya City. The implementation of community service is carried out through socialization and data collection by examining each cadre in a Germas event. The participants who did the ABO blood type examination were 32 people (78%) out of a total of 41 people. The results that have been achieved in knowing the type of ABO blood group are the number of data base types of blood type A as many as 7 people (22%), B as many as 7 people (22%), AB as many as 3 people (9%) and O as many as 15 people ( 47%)

Characterization of the DuPont photopolymer for three-dimensional holographic storage

DuPont's HRF-150 photopolymer film is investigated for use in three-dimensional holographic memories. Measurements of sensitivity, hologram persistence, the lateral spread of the photoinitiated reaction, and the variation of diffraction efficiency with modulation depth, spatial frequency and tilt angle, and intensity are reported. We observed that the diffraction efficiency of the HRF-150 photopolymer for a given exposure decreases with increases in intensity and grating tilt angle. The holograms were nondestructively reconstructed for long periods of time at room temperature. The photoinitiated reaction spread less than 100 µm over a period of 16 h

Mormonism in Illinois 1839-1847: a study of the development of socio-religious conflict

This thesis is a sociological account of the development of conflict between a religious group, the Mormons, and the society which acted as their host, mid nineteenth century Illinois. It traces the deterioration of the relationship between the Mormons and their host from one of friendly sympathy to one of open warfare, and seeks to explain this decline with the aid of sociological concepts. It does not attempt to put forward a theory of conflict, nor to give a history of Mormonism in Illinois. Rather, it attempts to give as full an account as possible of one instance of conflict and place this particular sect in its social and historical context. The thesis first considers whether social-structural conditions in Illinois, prior to Mormon entry, in conjunction with the scapegoat theory of prejudice, can help to explain the generation of hostility. It then goes on to consider possible alternative explanations emphasising the interaction between Mormon and Gentile within the context of Illinois society. The analysis concerns itself with the reasons why the Mormons were welcomed into the state and the possible influence which Gentile expectations had on subsequent definition of the Mormons as deviant. The escalating effects of the failure of two strategies designed to win the struggle, namely, the use of institutional facilities and mounting a moral crusade, are then examined. This is followed by an assessment of the reasons for the deterioration of the situation into violence and for the routinisation of this violent response. Finally, the effect of the conflict experience upon the development of the Mormons as a religious sect is considered

Heat shock protein 27 is a potential indicator for response to YangZheng XiaoJi and chemotherapy agents in cancer cells

Heat shock protein 27 (HSP27) is a member of the heat shock protein family which has been linked to tumour progression and, most interestingly, to chemotherapy resistance in cancer patients. The present study examined the potential interplay between HSP27 and YangZheng XiaoJi, a traditional Chinese medicine used in cancer treatment. A range of cell lines from different tumour types including pancreatic, lung, gastric, colorectal, breast, prostate and ovarian cancer (both wild-type and resistant) were used. Levels and activation of HSP27 and its potential associated signalling pathways were evaluated by protein array and western blotting. Knockdown of HSP27 in cancer cells was achieved using siRNA. Localisation and co-localisation of HSP27 and other proteins were carried out by immunofluorescence. Cell growth and migration were evaluated in their response to a range of chemotherapeutic agents. The present study first identified, by way of protein array, that YangZheng XiaoJi was able to inhibit the phosphorylation of HSP27 protein in cancer cells. We further demonstrated that HSP27, which is co-localised with caspase-9, can be blocked from localising in focal adhesions and co-localising with caspase-9 by YangZheng XiaoJi. The study also demonstrated that YangZheng XiaoJi was able to sensitise cancer cells including those cells that were resistant to chemotherapy, to chemotherapeutic agents. Finally, knocking down HSP27 markedly reduced the migration of cancer cells and increased the sensitivity of cancer cells to the inhibitory effect on cellular migration by YangZheng XiaoJi. YangZheng XiaoJi can act as an agent in first sensitising cancer cells to chemotherapy and secondly to overcome, to some degree, chemoresistance when used in an appropriate fashion in patients who have active HSP2