Harnessing Transition Metal Scaffolds for Targeted Antibacterial Therapy.

Antimicrobial resistance, caused by persistent adaptation and growing resistance of pathogenic bacteria to overprescribed antibiotics, poses one of the most serious and urgent threats to global public health. The limited pipeline of experimental antibiotics in development further exacerbates this looming crisis and new drugs with alternative modes of action are needed to tackle evolving pathogenic adaptation. Transition metal complexes can replenish this diminishing stockpile of drug candidates by providing compounds with unique properties that are not easily accessible using pure organic scaffolds. We spotlight four emerging strategies to harness these unique properties to develop new targeted antibacterial agents.

Fibroblast-derived matrices-based human skin equivalent as an in vitro psoriatic model for drug testing.

Psoriasis is a chronic skin disease characterized by thickening and disorganization of the skin's protective barrier. Although current models replicate some aspects of the disease, development of therapeutic strategies have been hindered by absence of more relevant models. This study aimed to develop and characterize an in vitro psoriatic human skin equivalent (HSE) using human keratinocytes HaCat cell line grown on fibroblasts-derived matrices (FDM). The constructed HSEs were treated with cytokines (IL-1α, TNF-α, IL-6, and IL22) to allow controlled induction of psoriasis-associated features. Histological stainings showed that FDMHSE composed of a fully differentiated epidermis and fibroblast-populated dermis comparable to native skin and rat tail collagen-HSE. Hyperproliferation (CK16 and Ki67) and inflammatory markers (TNF-α and IL-6) expression were significantly enhanced in the cytokine-induced FDM- and rat tail collagen HSEs compared to non-treated HSE counterparts. The characteristics were in line with those observed in psoriasis punch biopsies. Treatment with all-trans retinoic acid (ATRA) has shown to suppress these effects, where HSE models treated with both ATRA and cytokines exhibit histological characteristics, hyperproliferation and differentiation markers expression like non-treated control HSEs. Cytokine-induced FDM-HSE, constructed entirely from human cell lines, provides an excellent opportunity for psoriasis research and testing new therapeutics.

Helicobacter pylori Eradication in Parkinson's Disease: A Randomized Placebo-Controlled Trial.

BACKGROUND: Helicobacter pylori (HP) infection has been associated with worse motor function in Parkinson's disease (PD). OBJECTIVE: We aimed to evaluate the effects of HP eradication on PD symptoms. METHODS: In this parallel-group, double-blind, randomized placebo-controlled, single-center trial, patients with PD with positive HP urea breath test and serology were block randomized (1:1) to receive standard eradication triple therapy or identically appearing placebo capsules for 1 week. Prespecified motor (International Parkinson and Movement Disorder Society Unified PD Rating Scale [MDS-UPDRS], timed tests, and home-based wearable sensor measurements), nonmotor (Leeds Dyspepsia Questionnaire and Montreal Cognitive Assessment), and quality-of-life (Parkinson's Disease Questionnaire-39) outcome measures were assessed at weeks 6, 12, 24, and 52. The primary outcome was the baseline-to-week 12 change in ON medication MDS-UPDRS motor scores. Lactulose-hydrogen breath testing for concomitant small intestinal bacterial overgrowth was performed at baseline and repeated at week 24, together with the urea breath test. RESULTS: A total of 310 patients were screened for eligibility and 80 were randomly assigned, of whom 67 were included in the full-analysis set (32 treatment group patients, 35 placebo patients). HP eradication did not improve MDS-UPDRS motor scores at week 12 (mean difference 2.6 points in favor of placebo, 95% confidence interval: -0.4 to 5.6, P = 0.089). There was no significant improvement in any motor, nonmotor, or quality-of-life outcome at weeks 12 and 52. Both the full-analysis and per-protocol analyses (based on eradication status) supported these conclusions. Small intestinal bacterial overgrowth status did not influence treatment results. CONCLUSIONS: HP eradication does not improve clinical outcomes in PD, suggesting that there is no justification for routine HP screening or eradication with the goal of improving PD symptoms. © 2020 International Parkinson and Movement Disorder Society.

Case report of a maxillary antrolith.

INTRODUCTION: Antroliths, which are pathological calcifications within the maxillary sinus, are a rare occurrence. While some may present with symptoms, most maxillary antroliths are asymptomatic incidental findings. PRESENTATION OF CASE: We report a case of a 67-year-old lady with a round radiopacity within her right maxillary sinus as seen on the panoramic radiograph. Subsequent cone beam computed tomography (CBCT) scan detailed a well circumscribed radiopacity at the floor of the maxillary sinus. Surgical excision was done via Caldwell-Luc procedure. DISCUSSION: A review of literature was carried out with particular reference to the etiology, clinical and radiographic features and management of antroliths. Radiological examination of the sinus by standard Waters, panoramic radiograph and CT scan can aid in identification and diagnosis. While biopsy may be indicated to rule out differential diagnoses with similar presentations, in otherwise small and asymptomatic antroliths, they are generally left alone and periodic check-ups appear to be the primary choice of treatment. Surgical removal is considered the treatment of choice for antroliths with complications. CONCLUSION: With regular long term follow ups, prophylactic removal of small and asymptomatic antroliths may not be necessary. However, treatment options should be presented to the patient and the ultimate decision lies with the patient with informed consent taken.

Barriers to implementing a national health screening program for men in Malaysia: An online survey of healthcare providers

@#Introduction: This study aimed to determine the views and practices of healthcare providers and barriers they encountered when implementing the national health screening program for men in a public primary care setting in Malaysia. Methods: An online survey was conducted among healthcare providers across public health clinics in Malaysia. All family medicine specialists, medical officers, nurses and assistant medical officers involved in the screening program for adult men were invited to answer a 51-item questionnaire via email or WhatsApp. The questionnaire comprised five sections: participants’ socio-demographic information, current screening practices, barriers and facilitators to using the screening tool, and views on the content and format of the screening tool. Results: A total of 231 healthcare providers from 129 health clinics participated in this survey. Among them, 37.44% perceived the implementation of the screening program as a “top-down decision.” Although 37.44% found the screening tool for adult men “useful,” some felt that it was “time consuming” to fill out (38.2%) and “lengthy” (28.3%). In addition, ‘adult men refuse to answer’ (24.1%) was cited as the most common patient-related barrier. Conclusions: This study provided useful insights into the challenges encountered by the public healthcare providers when implementing a national screening program for men. The screening tool for adult men should be revised to make it more user-friendly. Further studies should explore the reasons why men were reluctant to participate in health screenings, thus enhancing the implementation of screening programs in primary care.

Pitted keratolysis: a clinical review.

BACKGROUND: Pitted keratolysis is a bacterial infection that affects the plantar epidermis. Despite the condition being reported in many countries affecting both shod and unshod populations, there is little guidance for clinicians providing evidence or best practice guidelines on the management of this often stubborn infection. METHODS: Using a structured search of a range of databases, papers were identified that reported treatments tested on patients with the condition. RESULTS: Most of the literature uncovered was generally of a low level, such as case-based reporting or small case series. Studies were focused mainly on the use of topical antibiotic agents, such as clindamycin, erythromycin, fusidic acid, and mupirocin, often in combination with other measures, such as hygiene advice and the use of antiperspirants. From the limited evidence available, the use of topical antibiotic agents shows some efficacy in the treatment of pitted keratolysis. However, there is currently no suggestion that oral antibiotic drug therapy alone is effective in managing the condition. CONCLUSIONS: Currently, there is no consensus on the most effective approach to managing pitted keratolysis, but a combination of antimicrobial agents and adjunctive measures, such as antiperspirants, seems to demonstrate the most effective approach from the current literature available.

Ferrocenyl catechols: synthesis, oxidation chemistry and anti-proliferative effects on MDA-MB-231 breast cancer cells.

The synthesis and anti-tumoral properties of a series of compounds possessing a ferrocenyl group tethered to a catechol via a conjugated system is presented. On MDA-MB-231 breast cancer cell lines, the catechol compounds display a similar or greater anti-proliferative potency (IC(50) values ranging from 0.48-1.21 µM) than their corresponding phenolic analogues (0.57-12.7 µM), with the highest activity found for species incorporating the [3]ferrocenophane motif. On the electrochemical timescale, phenolic compounds appear to oxidize to the quinone methide, while catechol moieties form the o-quinone by a similar mechanism. Chemical oxidation of selected compounds with Ag(2)O confirms this interpretation and demonstrates the probable involvement of such oxidative metabolites in the in vitro activity of these species.

Synthesis, oxidation chemistry and cytotoxicity studies on ferrocene derivatives of diethylstilbestrol.

A series of compounds is described in which one of the ethyl groups in diethylstilbestrol has been replaced by a ferrocenyl substituent. Only those derivatives incorporating phenol moieties underwent isomerisation from the Z to the E form, and some of them could be chemically oxidized to a quinone species. The compounds were less cytotoxic against hormone-independent MDA-MB-231 breast cancer cell lines than their corresponding ferrocenyl phenyl or phenol isomers in which the ferrocene and ethyl moieties are linked to the same carbon atom. The biochemical results were evaluated in conjunction with information obtained from electrochemical and chemical oxidation experiments.

Directed evolution of D-lactonohydrolase by error prone PCR and DNA shuffling / 生物工程学报

D-lactonohydrolase is useful in the procedure of resolution of racemic pantolactone to produce D-pantolactone, but the activity and stability under low pH of the wild type enzyme is not satisfactory enough to be applied to industrial production. The expected properties of wild type enzyme were enhanced by directed evolution. According to the formation of products and pH indicators, a screening system was designed. After three sequential error prone PCR and one round DNA shuffling followed by screening, Mut E-861, the best mutant with improved activity and stability under low pH situation was obtained. Gene analysis of the Mut E-861 mutant indicated that the mutant enzyme had A352C, G721A mutations and a silent mutation of position 1038. Moreover, the activity and stability of Mut E-861 were determined. The results showed that the activity of this mutant was 5.5-fold higher than that of wild type, and the stability under low pH was improved at no expense of D-lactonohydrolase activity. After incubated at pH 6.0 and pH 5.0 the activity of D-lactonohydrolase could be retained 75% to 50%, however, compared with 40% to 20% for wild type.

Control of Ammonia Pollution in Indoor Air / 环境与健康杂志

Objective To understand the ammonia pollution level in indoor air in Chengdu city,China.Methods 50 newly decorated houses included resident houses,offices and public places were selected in Chengdu city.The national standard method of China-Berthelot spectrophotometry was used to determine the concentration of ammonia in indoor air.Results The result showed that the average concentration of ammonia was 0.307 mg/m3,the rate of exceed standard limit was 58.33%,the highest concentration was 0.598 mg/m3,which was almost three times of the national standard limit.At 4 months after decoration,the concentration of ammonia decreased near to the national standard limit(0.20 mg/m3).Conclusion As the time goes on,the concentration of ammonia in indoor air shows a downtrend,and in general,it will reach to the safe level in 4 months after decoration,so it is suggested to move in the newly decorated houses after five months since the decoration finished will be better for human health.