Step-function luminopsins for bimodal prolonged neuromodulation

Although molecular tools for controlling neuronal activity by light have vastly expanded, there are still unmet needs which require development and refinement. For example, light delivery into the brain is still a major practical challenge that hinders potential translation of optogenetics in human patients. In addition, it would be advantageous to manipulate neuronal activity acutely and precisely as well as chronically and non-invasively, using the same genetic construct in animal models. We have previously addressed these challenges by employing bioluminescence and have created a new line of opto-chemogenetic probes termed luminopsins by fusing light-sensing opsins with light-emitting luciferases. In this report, we incorporated Chlamydomonas channelrhodopsin 2 with step-function mutations as the opsin moiety in the new luminopsin fusion protein termed step-function luminopsin (SFLMO). Bioluminescence-induced photocurrent lasted longer than the bioluminescence signal due to very slow deactivation of the mutated channel. In addition, bioluminescence was able to activate most of the channels on the cell surface due to the extremely high light sensitivity of the channel. This efficient channel activation was partly mediated by radiationless bioluminescence resonance energy transfer due to the proximity of luciferase and opsin. To test the utility of SFLMOs in vivo, we transduced the substantia nigra unilaterally via a viral vector in male rats. Injection of the luciferase substrate as well as conventional photostimulation via fiber optics elicited circling behaviors. Thus, SFLMOs expand the current approaches for manipulation of neuronal activity in the brain and add more versatility and practicality to optogenetics in freely behaving animals.     

An educational intervention to update health workers about HIV and infant feeding

Clinical guidelines are used to translate research findings into evidence‐based clinical practice but are frequently not comprehensively adopted by health workers (HWs). HIV and infant feeding guidelines were revised by the World Health Organization to align feeding advice for HIV‐exposed and unexposed infants, and these were adopted in South Africa in 2017. We describe an innovative, team‐based, mentoring programme developed to update HWs on these guidelines. The intervention was underpinned by strong theoretical frameworks and aimed to improve HWs' attitudes, knowledge, confidence, and skills about breastfeeding in the context of HIV. On‐site workshops and clinical mentoring used interactive participatory methods and a simple low‐tech approach, guided by participants' self‐reported knowledge gaps. Workshops were conducted at 24 participating clinics over three sessions, each lasting 1–2 hr. Evaluation data were collected using a self‐administered questionnaire. Of 303 participating HWs, 249/303 (82.2%) attended all workshops. Achieving high workshop attendance was challenging and “catch‐up” sessions were required to achieve good coverage. Common knowledge gaps identified included antiretroviral therapy adherence monitoring during breastfeeding and management of viral load results (173 participants), management of breast conditions (79), and advice about expressing and storing breastmilk (64). Most participants reported all their knowledge gaps were addressed and anticipated that their practice would change. We describe a feasible, sustainable approach to updating HWs on HIV and infant feeding guidelines and improving skills in breastfeeding counselling in resource‐constrained settings. This approach could be adapted to other topics and, with further evaluation, implemented at scale using existing resources.     

Tabakprävention in Deutschland und international

In Germany, several tobacco control policies have been implemented since 2002. These include tobacco tax increases, restrictions on sale and advertising, smoke-free legislation, and health warnings on tobacco products. All of those contributed to the emerging trend towards nonsmoking – especially among youth and young adults – as well as to the impressive decline of cigarette sales from 145.1 billion cigarettes in 2002 to 75.8 billion in 2017. Despite this, still 13% of all deaths are attributable to smoking in Germany.Other countries are acting in a more committed manner and are implementing much stronger tobacco control policies than Germany. Germany is the only EU country that doesn’t yet have a billboard ban on tobacco advertising, the smoke-free legislation is weak due to exceptions, and for more than ten years the tobacco tax has not been markedly increased. Globally, more than 30 countries have implemented at the highest possible level four of the six most important tobacco control policies as defined by the World Health Organization – Germany has implemented only two policies. Therefore, on an international scale, Germany is clearly lagging behind in tobacco control and on the European Tobacco Control Scale it is ranked second last. A more committed and compelling approach towards tobacco control is required in Germany to reach a position in terms of protecting the population from the devastating health hazards of smoking, which would be appropriate for a leading industrial nation.     

Arzneimitteltherapiesicherheit im Krankenhaus

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Arzneimittelbezogene Probleme (ABP) sind eine signifikante und häufig vermeidbare Ursache für Morbidität und...     

Experimentelle Untersuchungen zum Einfluß der Ovarialhormone auf die Entwicklung der Rattenmandibula

Zusammenfassung Weiblichen Ratten des Wistar-Stammes wurden am 1. oder 2. Lebenstag die Ovarien entfernt. Intakte Wurfgeschwister dienten als Kontrolltiere. An den mazerierten Unterkiefern erfolgten Flächen- sowie Längen- und Streckenmessungen von der Geburt an bis zur Pubertät. Es zeigte sich, daß insgesamt die Wachstumsraten bei den neonatal ovarektomierten Tieren im Vergleich zur Kontrollgruppe geringer waren. Deutliche Unterschiede wurden vor allem an den Mandibularflächen und im Vertikaldurchmesser des Kondylarbereiches gefunden. Der Flächeninhalt der Mandibulae stieg im Untersuchungszeitraum auf das 6fache, die Fläche im Bereich der Kondylen vergrößerte sich im gleichen Zeitraum auf das 14fache. Aus den Ergebnissen kann gefolgert werden, daß das Wachstum der Mandibula durch die niedrige präpubertale Sekretion der Ovarialhormone stimuliert wird. Den stärkeren Einfluß üben aber wahrscheinlich andere Wuchsfaktoren, z. B. Wachstumshormon, Schilddrüsenhormone, Androgene und wahrscheinlich das Insulin aus.

---

Summary Female rats of a Wistar strain were ovariectomized on the first day of life. Intact littermates served as controls. The growth of the mandibles was evaluated from birth till puberty by measuring the total area as well as the length and the distance between different points. The results demonstrated a generally lower mandibular growth in the neonatally castrated females as compared to the intact controls. Significant differences were mainly found in the total area of the mandible as well as in the vertical diameter of the condyles. Throughout the period of investigation, the total area of the mandibles increased 6fold and that of the condyles 14fold. The findings suggest that the relatively low oestrogen secretion during the prepubertal development stimulates mandibular growth, but that the predominant influence may be exerted by other growth factors, e. g. growth hormone, thyroid hormones, androgens and probably insulin.

---

Résumé Des rates de la colonie Wistar furent ovariectomisées un ou deux jours après la naissance. Des soeurs intactes servirent de contrôle. Depuis la naissance jusqu'à la puberté, on mesura la croissance des mandibules, tant sur leur surface totale que sur leur longueur et on nota la distance séparant différents points donnés. Les résultats ont montré une croissance mandibulaire généralement inférieure chez les femelles châtrées, dans la période néonatale, par rapport aux femelles intactes du groupe de contrôle. On observa des différences significatives dans la surface mandibulaire, ainsi que dans le diamètre vertical de la région condylienne. La surface totale des mandibules augmenta de 6 fois et celle des condyles de 14 fois pendant la période d'observation. On pourrait conclure, au vu des résultats obtenus, que la croissance mandibulaire est stimulée par la sécrétion prépubérale relativement basse d'oestrogènes, mais que l'influence prédominante appartient probablement à d'autres facteurs de croissance, tels que l'hormone de croissance, les hormones thyroidiennes, les androgènes et probablement l'insuline.

---

---

Herrn OMR Prof. Dr. med. habil.R. Fränkel zum 75. Geburtstag, vorgetragen beim Geburtstagssymposium in Reinhardsbrunn.     

Free flap transfer for closure and interposition-arthroplasty in noma defects of the lateral face associated with bony ankylosis

Noma defects of the anterolateral face are often associated with fibrous or bony ankylosis fusing the mandibula to the skull base. According to the extent of the ankylosis, the temporomandibular joint mobility can be restricted or even completely frozen. In third world conditions the surgical approach to severe forms of bony ankylosis consists of a single linear opening osteotomy (trismus release) and the closure of the noma defect with locoregional flaps. Relapse of jaw immobility is common and may be caused by minor bone resection, the lack of adequate postoperative physiotherapy, or even the scarring of the defect coverage.In 4 years the authors have gained increasing experience with folded free flaps for simultaneous closure of outer and inner lining of large noma defects and the maintenance and training of re-established jaw function by the use of a dynamic external distractor fixed between the zygoma and the mandibular body. The authors report the bony reankylosis can be reduced by extended wedge osteotomies of the bony bridge and tip-like shaping of the ascending mandibular ramus. To preclude the reossification of the osteotomy site and fibrous scar formation, a dermofatty or muscular tail of the free flap is interposed into the bone gap. Two cases were treated according to this concept with a free parascapular and a latissimus dorsi flap in combination with simultaneous arthroplasty. During a 6-month follow-up period, no signs of a recurrent reduction of mandibular movement were noted in either case.     

Plaque and gingivitis in the elderly: a randomized, single-blind clinical trial on the outcome of intensified mechanical or antibacterial oral hygiene measures

OBJECTIVES: To study the outcome of intensified mechanical oral hygiene compared with the effect of an adjunctive antibacterial mouth rinse on plaque and gingivitis in elderly people. MATERIAL AND METHODS: In a randomized, single-blind, 6-month controlled clinical study, 106 subjects, 55 years or older, were divided into four groups: (I) Participants were instructed on improved mechanical oral hygiene, including interdental hygiene; (II) subjects used an antibacterial mouth rinse containing amine and stannous fluoride in addition to their usual oral hygiene practices; (III) both intensive mechanical and antibacterial measures were combined; and (IV) a control group with no specific regimen. Gingivitis and plaque were examined. RESULTS: After 6 months, both plaque and gingivitis scores were significantly lower than at baseline in all groups. Reductions in gingivitis differed significantly between the control group and all other groups but not between the three intervention groups. Only groups with improved mechanical oral hygiene showed significant improvements in plaque scores compared with control. CONCLUSIONS: Intensive mechanical oral hygiene resulted in greater plaque reduction than the combination of an antibacterial rinse and usual oral hygiene procedures. Gingivitis was reduced by both intensive oral hygiene and use of the amine/stannous fluoride rinse. Combining intensive mechanical oral hygiene with the antibacterial rinse did not result in further gingivitis reduction.