Monogenic etiologies of persistent human papillomavirus infections: A comprehensive systematic review.

PURPOSE: Persistent human papillomavirus infection (PHPVI) causes cutaneous, anogenital, and mucosal warts. Cutaneous warts include common warts, Treeman syndrome, and epidermodysplasia verruciformis, among others. Although more reports of monogenic predisposition to PHPVI have been published with the development of genomic technologies, genetic testing is rarely incorporated into clinical assessments. To encourage broader molecular testing, we compiled a list of the various monogenic etiologies of PHPVI. METHODS: We conducted a systematic literature review to determine the genetic, immunological, and clinical characteristics of patients with PHPVI. RESULTS: The inclusion criteria were met by 261 of 40,687 articles. In 842 patients, 83 PHPVI-associated genes were identified, including 42, 6, and 35 genes with strong, moderate, and weak evidence for causality, respectively. Autosomal recessive inheritance predominated (69%). PHPVI onset age was 10.8 ± 8.6 years, with an interquartile range of 5 to 14 years. GATA2,IL2RG,DOCK8, CXCR4, TMC6, TMC8, and CIB1 are the most frequently reported PHPVI-associated genes with strong causality. Most genes (74 out of 83) belong to a catalog of 485 inborn errors of immunity-related genes, and 40 genes (54%) are represented in the nonsyndromic and syndromic combined immunodeficiency categories. CONCLUSION: PHPVI has at least 83 monogenic etiologies and a genetic diagnosis is essential for effective management.

Cancerous Tissue Diagnosis by LIF Spectroscopy Derived From Body-Compatible Fluorophores.

Introduction: The laser-induced fluorescence (LIF) method as molecular emission spectroscopy is used to diagnose cancerous tissues. According to the previous reports, the red-shift in the fluorescence spectrum from Rhodamine 6G (Rd6G)-stained cancerous tissues compared to healthy ones impregnated with the same dye provides the feasibility for diagnosis. In this paper, we have employed the LIF emissions as a diagnostic method to distinguish between cancerous and healthy tissues infiltrated by a body-compatible fluorophore to avoid the toxicity and hazard of Rd6G dye. Methods: Biological tissue specimens are stained with sodium fluorescein (NaFl) dye and then irradiated by the blue CW diode laser (405 nm) to examine the spectral properties that are effective in detecting cancerous tissues. Results: The spectral shift and the intensity difference of fluorescence are keys to diagnosing in vitro cancerous breast, colon, and thyroid tissues for clinical applications. The notable tubular densities in the breast and colon tissues and the space between the papillae in the thyroid ones cause the cancerous tissues to be prominently heterogeneous, providing numerous micro-cavities and thus more room for dye molecules. Conclusion: Here, we have assessed the spectral shift and intensity difference of fluorescence as a diagnostic method to distinguish between cancerous and healthy tissues for clinical applications.

National food policies in the Islamic Republic of Iran aimed at control and prevention of noncommunicable diseases.

BACKGROUND: Diet plays an important role in the risk of noncommunicable diseases. In the Islamic Republic of Iran, national activities were started after release of the World Health Organization's (WHO) action plan on prevention and control of noncommunicable diseases. AIMS: This study describes national food policies implemented by the government in order to reduce noncommunicable diseases in the country in line with WHO action plan. METHODS: Newly adopted food standards and regulations linked to noncommunicable diseases from 2013 to 2018 were reviewed and the maximum permitted levels of salt and trans and saturated fats were compared in the old and new standards. Nutritional traffic light labelling to raise public awareness of healthy diets was evaluated. RESULTS: Fifteen food standards associated with eight food items that make up a large share of the daily Iranian food basket and three that make up a small share were evaluated. Policies on salt included reduction in maximum permitted percentage in bread, cheese and doogh (a fermented drink) to 1%, 3% and 0.8%, respectively. For trans and saturated fats, maximum permitted percentages were set as 2-5% and 30-65% of edible oils and fats, respectively. Nutritional traffic light labelling, which indicates the content of salt, sugar, fat and trans fat in foods, has been mandatory for all foods since 2016. CONCLUSIONS: In view of the polices implemented to reduce the salt and fat/oil content of foods, significant decreases in noncommunicable diseases are expected in coming years in the country. However, further studies are needed to show the effectiveness of the interventions.

Quantitation of Six Alternaria Toxins in Infant Foods Applying Stable Isotope Labeled Standards.

Alternaria fungi are widely distributed saprophytes and plant pathogens. As pathogens, Alternaria fungi infect crops and vegetables and cause losses in the fields and during postharvest storage. While farmers suffer from declining yields, consumers are endangered by the formation of secondary metabolites, because some of these exhibit a pronounced toxicological potential. The evaluation of the toxicological capabilities is still ongoing and will contribute to a valid risk assessment. Additionally, data on the incidence and the quantity of Alternaria mycotoxins found in food products is necessary for dietary exposure evaluations. A sensitive LC-MS/MS method for the determination of the Alternaria mycotoxins alternariol (AOH), alternariol monomethylether (AME), tentoxin (TEN), altertoxin I (ATX I), alterperylenol (ALTP), and tenuazonic acid (TA) was developed. AOH, AME, and TA were quantified using stable-isotopically labeled standards. TEN, ATX I, and ALTP were determined using matrix matched calibration. The developed method was validated by using starch and fresh tomato matrix and resulted in limits of detection ranging from 0.05 to 1.25 µg/kg for starch (as a model for cereals) and from 0.01 to 1.36 µg/kg for fresh tomatoes. Limits of quantification were determined between 0.16 and 4.13 µg/kg for starch and between 0.02 and 5.56 µg/kg for tomatoes. Recoveries varied between 83 and 108% for starch and between 95 and 111% for tomatoes. Intra-day precisions were below 4% and inter-day precisions varied from 3 to 8% in both matrices. Various cereal based infant foods, jars containing vegetables and fruits as well as tomato products for infants were analyzed for Alternaria mycotoxin contamination (n = 25). TA was the most frequently determined mycotoxin and was detected in much higher contents than the other toxins. AME and TEN were quantified in many samples, but in low concentrations, whereas AOH, ATX I, and ALTP were determined rarely, among which AOH had higher concentration. Some infant food products were highly contaminated with Alternaria mycotoxins and the consumption of these individual products might pose a risk to the health of infants. However, when the mean or median is considered, no toxicological risk was obvious.

Lead and cadmium levels in raw bovine milk and dietary risk assessment in areas near petroleum extraction industries.

Oil fields are a source of heavy metal pollution, but few studies have evaluated its impact on the intake of these contaminants through milk, an important food especially for children. From February 2015 to 2016, 118 samples of raw cow's milk, 14 of fodder and 8 of water in Southwest Iran were collected from farms close to oil fields or related industries. Lead (Pb) and cadmium (Cd) levels were evaluated by graphite furnace atomic absorption spectrometry. Mean±SE in milk and fodder were 47.0±3.9 and 54.0±6.9µg/kg for Pb, and 4.7±1.0 and 3.5±1.3µg/kg for Cd. No Pb or Cd was detected in water. Most milk samples (82.2%) for Pb were above the permissible limits (20µg/kg). Exposure to Pb and Cd from milk consumption was calculated in two scenarios: mean and maximum exposure for the age range of 2-90years. The intake of an average Iranian adult (25years, 60kg b. w., 0.14kg milk/day) would be 6.6µg Pb and 0.66µg Cd/day (WI of 46.2 and 4.6µg, respectively), well below the risk values proposed by some international organizations, even in the maximum exposure scenario. However, Pb exposure for infants and toddlers may be closer to the risk values, since milk and milk products could be the main contributor to Cd and Pb, and small children consume 2-3 times more food than adults relative to their body weight. The risk of Pb and Cd exposure through milk close to oil fields should be considered and a monitoring plan for these contaminants is strongly recommended.

Manganese Compounds as Water-Oxidizing Catalysts: From the Natural Water-Oxidizing Complex to Nanosized Manganese Oxide Structures.

All cyanobacteria, algae, and plants use a similar water-oxidizing catalyst for water oxidation. This catalyst is housed in Photosystem II, a membrane-protein complex that functions as a light-driven water oxidase in oxygenic photosynthesis. Water oxidation is also an important reaction in artificial photosynthesis because it has the potential to provide cheap electrons from water for hydrogen production or for the reduction of carbon dioxide on an industrial scale. The water-oxidizing complex of Photosystem II is a Mn-Ca cluster that oxidizes water with a low overpotential and high turnover frequency number of up to 25-90 molecules of O2 released per second. In this Review, we discuss the atomic structure of the Mn-Ca cluster of the Photosystem II water-oxidizing complex from the viewpoint that the underlying mechanism can be informative when designing artificial water-oxidizing catalysts. This is followed by consideration of functional Mn-based model complexes for water oxidation and the issue of Mn complexes decomposing to Mn oxide. We then provide a detailed assessment of the chemistry of Mn oxides by considering how their bulk and nanoscale properties contribute to their effectiveness as water-oxidizing catalysts.

Nanoethosomes mediated transdermal delivery of vinpocetine for management of Alzheimer's disease.

AIM: To develop and statistically optimize nanoethosomal formulation for transdermal delivery of vinpocetine as an anti-Alzheimer's drug. MATERIALS AND METHODS: Box-Behnken experimental design was applied for optimization of nanoethosomes. The independent variables were phospholipid (X1), Tween 80 (X2) and Ethanol (X3) while entrapment efficiency (Y1), particle sizes (Y2), elasticity (Y3) and flux (Y4) were the dependent variables. RESULTS AND CONCLUSION: Optimized nanoethosomal vinpocetine formulation with mean particle size 50.57 ± 26.11 nm showed 97.51 ± 0.86% entrapment efficiency, achieved mean transdermal flux 925.60 ± 39.80 µg/cm2/h and elasticity of 86.61 ± 2.88. Ex-vivo study of nanoethosomal formulation showed a significant increase flux and entrapment efficiency compared with control vinpocetine solution. Our results suggest that nanoethosome is an efficient carrier for transdermal delivery of vinpocetine as compared to its oral form.

The role of nano-sized manganese oxides in the oxygen-evolution reactions by manganese complexes: towards a complete picture.

Eighteen Mn complexes with N-donor and carboxylate ligands have been synthesized and characterized. Three Mn complexes among them are new and are reported for the first time. The reactions of oxygen evolution in the presence of oxone (2KHSO5·KHSO4·K2SO4) and cerium(iv) ammonium nitrate catalyzed by these complexes are studied and characterized by UV-visible spectroscopy, X-ray diffraction spectrometry, dynamic light scattering, Fourier transform infrared spectroscopy, electron paramagnetic resonance spectroscopy, transmission electron microscopy, scanning electron microscopy, membrane-inlet mass spectrometry and electrochemistry. Some of these complexes evolve oxygen in the presence of oxone as a primary oxidant. CO2 and MnO4(-) are other products of these reactions. Based on spectroscopic studies, the true catalysts for oxygen evolution in these reactions are different. We proposed that for the oxygen evolution reactions in the presence of oxone, the true catalysts are both high valent Mn complexes and Mn oxides, but for the reactions in the presence of cerium(iv) ammonium nitrate, the active catalyst is most probably a Mn oxide.

Fragments of layered manganese oxide are the real water oxidation catalyst after transformation of molecular precursor on clay.

A binuclear manganese molecular complex [(OH2)(terpy)Mn(µ-O)2Mn(terpy)(OH2)](3+) (1) is the most prominent structural and functional model of the water-oxidizing Mn complex operating in plants and cyanobacteria. Supported on montmorillonite clay and using Ce(IV) as a chemical oxidant, 1 has been reported to be one of the best Mn-based molecular catalysts toward water oxidation. By X-ray absorption spectroscopy and kinetic analysis of the oxygen evolution reaction, we show that [(OH2)(terpy)Mn(µ-O)2Mn(terpy)(OH2)](3+) is transformed into layered type Mn-oxide particles which are the actual water oxidation catalyst.

A simple mathematical model for manganese oxide-coated montmorillonite as a catalyst for water oxidation: from nano to macro sized manganese oxide.

Here, we propose a mathematical model that gives a good fit to the experimental data for water oxidation by Mn oxide-coated montmorillonite with different Mn content. Our data show that the water oxidation may progress by cooperation among only neighbor Mn ions on montmorillonite. It is a promising model for finding more about the mechanism of multi-electron reactions.

Biological water-oxidizing complex: a nano-sized manganese-calcium oxide in a protein environment.

The resolution of Photosystem II (PS II) crystals has been improved using isolated PS II from the thermophilic cyanobacterium Thermosynechococcus vulcanus. The new 1.9 Å resolution data have provided detailed information on the structure of the water-oxidizing complex (Umena et al. Nature 473: 55-61, 2011). The atomic level structure of the manganese-calcium cluster is important for understanding the mechanism of water oxidation and to design an efficient catalyst for water oxidation in artificial photosynthetic systems. Here, we have briefly reviewed our knowledge of the structure and function of the cluster.

Nano-sized manganese oxide: a proposed catalyst for water oxidation in the reaction of some manganese complexes and cerium(IV) ammonium nitrate.

According to UV-visible spectroscopy, X-ray diffraction spectrometry, dynamic light scattering, Fourier transform infrared spectroscopy, electron paramagnetic resonance spectroscopy, transmission electron microscopy, scanning electron microscopy and X-ray photoelectron spectroscopy, nano-sized manganese oxides are proposed as active catalysts for water oxidation in the reaction of some manganese complexes and cerium(IV) ammonium nitrate.

Biological water oxidation: lessons from nature.

Hydrogen production by water splitting may be an appealing solution for future energy needs. To evolve hydrogen efficiently in a sustainable manner, it is necessary first to synthesize what we may call a 'super catalyst' for water oxidation, which is the more challenging half reaction of water splitting. An efficient system for water oxidation exists in the water oxidizing complex in cyanobacteria, algae and plants; further, recently published data on the Manganese-calcium cluster have provided details on the mechanism and structure of the water oxidizing complex. Here, we have briefly reviewed the characteristics of the natural system from the standpoint of what we could learn from it to produce an efficient artificial system. In short, to design an efficient water oxidizing complex for artificial photosynthesis, we must learn and use wisely the knowledge about water oxidation and the water oxidizing complex in the natural system. This article is part of a Special Issue entitled: Photosynthesis Research for Sustainability: from Natural to Artificial.