The phenotypic and genotypic spectra of ichthyosis with confetti plus novel genetic variation in the 3' end of KRT10: from disease to a syndrome

Ichthyosis with confetti (IWC) is a genodermatosis caused by dominant negative mutations in the gene encoding keratin 10 (KRT10). We investigated clinical and genetic details of a substantial number of patients with IWC in order to define major and minor criteria for diagnosis of this rare disorder.; Parallel clinical investigation of 6 patients with IWC revealed a novel spectrum of phenotypes. We found several features that qualify as major criteria for diagnosis, which are clearly and consistently associated with the condition. These included malformation of ears, hypoplasia of mammillae, and dorsal acral hypertrichosis. Genetic analysis of patients revealed several different frameshift mutations in intron 6 or exon 7 of KRT10. Analysis of this locus in 17 unrelated control individuals revealed 2 novel polymorphisms of KRT10.; We present for the first time to our knowledge the spectrum of clinical variability of IWC in 6 patients with confirmed mutations in KRT10. From this, we have extracted major and minor criteria to aid early and correct clinical diagnosis. Ectodermal malformations, present in all patients, suggest a novel classification of IWC as a syndrome. There is remarkable genetic variation at the IWC disease locus within control individuals from the general population

A Search for Biologically Active Compounds for Potential Pharmaceutic and Agronomic Applications

Summarized here are some aspects of my research activities in Ciba-Geigy Central Research Laboratories (1985–1996), in Novartis and Syngenta Crop Protection Research (1997–2020). I have followed the chronological order of these research activities covering only published data

Photoactivated chemotherapy (PACT) : the potential of excited-state d-block metals in medicine

The fields of phototherapy and of inorganic chemotherapy both have long histories. Inorganic photoactivated chemotherapy (PACT) offers both temporal and spatial control over drug activation and has remarkable potential for the treatment of cancer. Following photoexcitation, a number of different decay pathways (both photophysical and photochemical) are available to a metal complex. These pathways can result in radiative energy release, loss of ligands or transfer of energy to another species, such as triplet oxygen. We discuss the features which need to be considered when developing a metal-based anticancer drug, and the common mechanisms by which the current complexes are believed to operate. We then provide a comprehensive overview of PACT developments for complexes of the different d-block metals for the treatment of cancer, detailing the more established areas concerning Ti, V, Cr, Mn, Re, Fe, Ru, Os, Co, Rh, Pt, and Cu and also highlighting areas where there is potential for greater exploration. Nanoparticles (Ag, Au) and quantum dots (Cd) are also discussed for their photothermal destructive potential. We also discuss the potential held in particular by mixed-metal systems and Ru complexes

Analysis of Nurse and Patient Preferences for Pre-Filled Pen Devices for Self-Injection of Highly Purified Human Menopausal Gonadotropin (HP-hMG, MENOPURR

PURPOSE: This study aimed to identify the most important attributes for a gonadotropin pen as perceived by assisted reproductive technology (ART) patients and fertility nurses, and to examine how well a prototype HP-hMG (MENOPUR PATIENTS AND METHODS: This market research study incorporated a two-part survey with respondents (N=221) from Poland, Spain and the UK. Respondents included patients (n=141) who consulted a fertility specialist in the previous 2 years, and fertility nurses (n=80) who assisted in at least 75 ART cycles/year. Patients were divided into two subgroups depending on their experience with ART (experienced and naïve). Key attributes for an injection pen, as perceived by patients and nurses, were assessed via an online survey and ranked by their relative importance using Anchored Maximum Difference Scaling. After performing a dummy injection, respondents compared the attributes of an unbranded prototype pen against the key attributes identified. RESULTS: Across all survey respondents, the ability to correct the dialed dose was considered to be the most important product attribute of a gonadotropin pen. Confidence in the patient\u27s ability to inject correctly at home was also identified as a key attribute, considered by both nurses and naïve patients as extremely high. When considering the prototype pen device, almost all study respondents reported a positive experience (99%) with 72% rating it as very good . The prototype pen was perceived to possess the key attributes considered important for a gonadotropin pen by patients and nurses, including correcting the dose, the ability to self-inject safely and correctly, ease of preparation and use, and an injection which appeared to be as painless as possible. CONCLUSION: The prototype pen was found to perform well across all key attributes, especially those considered most important in gonadotropin pens, suggesting that it is a user-friendly option for patients undergoing ART

Analysis of Nurse and Patient Preferences for Pre-Filled Pen Devices for Self-Injection of Highly Purified Human Menopausal Gonadotropin (HP-hMG, MENOPUR®)

PURPOSE: This study aimed to identify the most important attributes for a gonadotropin pen as perceived by assisted reproductive technology (ART) patients and fertility nurses, and to examine how well a prototype HP-hMG (MENOPUR PATIENTS AND METHODS: This market research study incorporated a two-part survey with respondents (N=221) from Poland, Spain and the UK. Respondents included patients (n=141) who consulted a fertility specialist in the previous 2 years, and fertility nurses (n=80) who assisted in at least 75 ART cycles/year. Patients were divided into two subgroups depending on their experience with ART (experienced and naïve). Key attributes for an injection pen, as perceived by patients and nurses, were assessed via an online survey and ranked by their relative importance using Anchored Maximum Difference Scaling. After performing a dummy injection, respondents compared the attributes of an unbranded prototype pen against the key attributes identified. RESULTS: Across all survey respondents, the ability to correct the dialed dose was considered to be the most important product attribute of a gonadotropin pen. Confidence in the patient\u27s ability to inject correctly at home was also identified as a key attribute, considered by both nurses and naïve patients as extremely high. When considering the prototype pen device, almost all study respondents reported a positive experience (99%) with 72% rating it as very good . The prototype pen was perceived to possess the key attributes considered important for a gonadotropin pen by patients and nurses, including correcting the dose, the ability to self-inject safely and correctly, ease of preparation and use, and an injection which appeared to be as painless as possible. CONCLUSION: The prototype pen was found to perform well across all key attributes, especially those considered most important in gonadotropin pens, suggesting that it is a user-friendly option for patients undergoing ART

ROLE OF BENZODIAZEPINES IN THE TREATMENT OF ANXIETY DISORDERS IN 2014

Background: This article aims at determining the place of benzodiazepines in the current treatment of anxiety disorders in opposition to antidepressants, neuroleptics and anticonvulsants. Belgium and France are the only two European countries which prescribe the most benzodiazepines despite the dissuasion of the international guidelines (NICE) issued in the nineties concerning the high risk of dependance of these molecules. What about the respect of these guidelines and the use of benzodiazepines in general practice in 2014? Methods: Review of the literature with the following key words «anxiety disorder, benzodiazepines, anxiolytic, treatment» in the international database of PubMed, Medline, PsycINFO, PsycARTICLES and consulting of various reference books. Results: No class of molecules could measure up to benzodiazepines until now, neither from the point of view of efficiency, nor from the point of view of cost-efficiency. This is why the guidelines (NICE) discourage the few available alternatives in the general practice. International figures from Belgium and France show a continuous increase in the use of benzodiazepines in the treatment of anxiety disorders, even after the nineties. Given the fact that benzodiazepines differ from one another at the level of their action profile (graphical representation in “stars”) and are therefore able to relieve several symptoms simultaneously, these molecules still respond nowadays to many expectations of the clinical practitioners. Conclusions: The divergence between the guidelines and the practice confirm the irreplaceability of benzodiazepines at the present time. Nevertheless, the expectation of new molecules with fewer side effects should be investigated in further research

Strigolactones: Plant Hormones with Promising Features

Almost 80 years after the discovery of the first plant hormone, auxin, a few years ago a new class of plant hormones, the strigolactones, was discovered. These molecules have unprecedented biological activity in a number of highly important biological processes in plants but also outside the plant in the rhizosphere, the layer of soil surrounding the roots of plants and teeming with life. The exploitation of this amazing biological activity is not without challenges: the synthesis of strigolactones is complicated and designing the desired activity a difficult task. This minireview describes the current state of knowledge about the strigolactones and how synthetic analogs can be developed that can potentially contribute to the development of a sustainable agriculture

Photochemically active DNA-intercalating ruthenium and related complexes – insights by combining crystallography and transient spectroscopy

Recent research on the study of the interaction of ruthenium polypyridyl compounds and defined sequence nucleic acids is reviewed. Particular emphasis is paid to complexes [Ru(LL)2(Int)]2+ containing potentially intercalating ligands (Int) such as dipyridophenazine (dppz), which are known to display light-switching or photo-oxidising behaviour, depending on the nature of the ancillary ligands. X-ray crystallography has made a key contribution to our understanding, and the first complete survey of structural results is presented. These include sequence, enantiomeric, substituent and structural specificities. The use of ultrafast transient spectrocopic methods to probe the ultrafast processes for complexes such as [Ru(TAP)2(dppz)]2+ and [Ru(phen)2(dppz)]2+ when bound to mixed sequence oligonucleotides are reviewed with particular attention being paid to the complementary advantages of transient (visible) absorption and time-resolved (mid) infra-red techniques to probe spectral changes in the metal complex and in the nucleic acid. The observed photophysical properties are considered in light of the structural information obtained from X-ray crystallography. In solution, metal complexes can be expected to bind at more than one DNA step, so that a perfect correlation of the photophysical properties and factors such as the orientation or penetration of the ligand into the intercalation pocket should not be expected. This difficulty can be obviated by carrying out TRIR studies in the crystals. Dppz complexes also undergo insertion, especially with mismatched sequences. Future areas for study such as those involving non-canonical forms of DNA, such as G-quadruplexes or i-motifs are also briefly considered