The Ser/Thr protein kinase AfsK regulates polar growth and hyphal branching in the filamentous bacteria Streptomyces

In cells that exhibit apical growth, mechanisms that regulate cell polarity are crucial for determination of cellular shape and for the adaptation of growth to intrinsic and extrinsic cues. Broadly conserved pathways control cell polarity in eukaryotes, but less is known about polarly growing prokaryotes. An evolutionarily ancient form of apical growth is found in the filamentous bacteria Streptomyces, and is directed by a polarisome-like complex involving the essential protein DivIVA. We report here that this bacterial polarization machinery is regulated by a eukaryotic-type Ser/Thr protein kinase, AfsK, which localizes to hyphal tips and phosphorylates DivIVA. During normal growth, AfsK regulates hyphal branching by modulating branch-site selection and some aspect of the underlying polarisome-splitting mechanism that controls branching of Streptomyces hyphae. Further, AfsK is activated by signals generated by the arrest of cell wall synthesis and directly communicates this to the polarisome by hyperphosphorylating DivIVA. Induction of high levels of DivIVA phosphorylation by using a constitutively active mutant AfsK causes disassembly of apical polarisomes, followed by establishment of multiple hyphal branches elsewhere in the cell, revealing a profound impact of this kinase on growth polarity. The function of AfsK is reminiscent of the phoshorylation of polarity proteins and polarisome components by Ser/Thr protein kinases in eukaryotes.     

Homozygous dystroglycan mutation associated with a novel muscle–eye–brain disease-like phenotype with multicystic leucodystrophy

Defects in dystroglycan post-translational modification result in congenital muscular dystrophy with or without additional eye and brain involvement, are referred to as secondary dystroglycanopathies and have been associated with mutations in 11 different genes encoding glycosyltransferases or associated proteins. However, only one patient with a mutation in the dystroglycan encoding gene DAG1 itself has been described before. We here report a homozygous novel DAG1 missense mutation c.2006G>T predicted to result in the amino acid substitution p.Cys669Phe in the β-subunit of dystroglycan in two Libyan siblings. The affected girls presented with a severe muscle–eye–brain disease-like phenotype with distinct additional findings of macrocephaly and extended bilateral multicystic white matter disease, overlapping with the cerebral findings in patients with megalencephalic leucoencephalopathy with subcortical cysts. This novel clinical phenotype observed in our patients further expands the clinical spectrum of dystroglycanopathies and suggests a role of DAG1 not only for dystroglycanopathies but also for some forms of more extensive and multicystic leucodystrophy.     

What do patients know about anesthesiologists? Results of a comparative survey in an U.S., Australian,and German university hospital

Study ObjectivesTo determine patients' knowledge of the role of the anesthesiologist in the hospital.DesignProspective survey instrument.SettingThree university hospitals (University of Virginia, Charlottesville, VA, USA; St. George Hospital University of New South Wales, Sydney, Australia; and University Hospital, Ruhr-University Bochum, Bochum, Germany).Patients900 patients (300 pts per center) undergoing elective surgery.MeasurementsPatients completed a standardized questionnaire before surgery and before speaking to an anesthesiologist.Main ResultsMost patients knew that anesthesiologists were medical doctors (Charlottesville, 58%; Bochum, 83%; Sydney, 71%). The majority (> 75%) underestimated the amount of training required to become anesthesiologist. While patients recognized the role of anesthesiologists in keeping patients asleep and awakening them, many patients did not understand the anesthesiologists' role in treating intraoperative medical problems. Patients had diverse concerns including infection, awakening during surgery, and failure to awaken, although patients were unclear about who was responsible for treating these issues. Outside the operating room (OR), 71% of patients rated Intensive Care Unit treatment as a duty of the anesthesiologist in Bochum, but fewer (P < 0.05) did so from Charlottesville (42%) and Sydney (49%). Understanding of duties outside the OR (resuscitation, teaching medical students, or chronic pain treatment) was very low (< 50%) in all centers.ConclusionPatients underestimated the training and role of the anesthesiologist in the OR and hospital.     

Orthographic cueing in anomic aphasia: How does it work?

Background: Both orthographic and phonological information from the target word can be appropriate cues in anomia treatment. Furthermore, both types of cues are used very frequently in clinical practice, although their underlying mechanisms of effectiveness and stability are still a matter of debate (e.g., Basso, Marangolo, Piras, & Galluzzi, 2001 Basso, A., Marangolo, P., Piras, F. and Galluzi, C. 2001. Acquisition of new “words” in normal participants: A suggestion for the treatment of anomia.. Brain and Language, 77: 45–59. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar]; Best, Herbert, Hickin, Osborne, & Howard, 2002 Best, W., Herbert, R., Hickin, J., Osborne, F. and Howard, D. 2002. Phonological and orthographic facilitation of word‐retrieval in aphasia: Immediate and delayed effects.. Aphasiology, 16: 151–168. [Taylor & Francis Online], [Web of Science ®] , [Google Scholar]; Howard & Harding, 1998 Howard, D. and Harding, D. 1998. Self‐cueing of word retrieval by a woman with aphasia: Why a letter board works.. Aphasiology, 12: 399–420. [Taylor & Francis Online], [Web of Science ®] , [Google Scholar]).

Aims: The aim of the study was to examine the mechanisms by which orthographic cues are effective in detail. The study addresses two questions. First, what is the relationship between sublexical transcoding ability and the effectiveness of orthographic cues? And second, what is the relationship between effectiveness of orthographic cues and effectiveness of phonological cues?

Methods & Procedures: Three people with chronic aphasia and moderate to severe anomia participated in facilitation of spoken naming, using either the initial phoneme or initial letter of the target word. Both immediate and delayed effects were assessed over six facilitation sessions. Orthographic and phonological cue effects were investigated with regard to regularity of orthographic‐phonological conversion (OPC) of the target's initial letter, and with regard to sub‐lexical and lexical reading and repetition in the participants using a multiple single‐case design (cf. Howard, 2003 Howard, D. 2003. “Single cases, group studies and case series in aphasia therapy.”. In The sciences of aphasia: From therapy to theory, Edited by: Papathanasiou, I and De Bleser, R. 245–258. Oxford, , UK: Elsevier Science Ltd. [Crossref] , [Google Scholar]).

Outcomes & Results: In one participant both phonological and orthographic cues produced similar effects. In the other two participants, orthographic cueing effects were present in the absence of phonological cueing effects. With regard to regularity of the initial letter‐phoneme conversion in the orthographic condition, a similar pattern overall was present for regular, ambiguous, and irregular target words, e.g., initial letter cues seemed to be similarly effective in words such as KNIFE (irregular OPC of initial letter) as in words such as KING or DOLL.

Conclusions: Initial letter cues are appropriate cues for the effective treatment of anomia as they may produce strong and long‐lasting effects. In contrast to earlier predictions (e.g., Bruce & Howard, 1988 Bruce, C. and Howard, D. 1988. Why don't Broca's aphasics cue themselves? An investigation of phonemic cueing and tip of the tongue information.. Neuropsychologia, 26: 253–264. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar]), initial letter cues may be effective even in participants where the initial phoneme cue remains totally ineffective. There are likely to be various mechanisms of effectiveness underpinning orthographic cue effects: a sub‐lexical mechanism and a lexical mechanism of effectiveness.     

Nasal Staphylococcus aureus carriage is not a risk factor for lower-airway infection in young cystic fibrosis patients

Staphylococcus aureus is one of the first pathogens which often persistently infect the airways of cystic fibrosis (CF) patients. Nasal S. aureus carriage is a risk factor for S. aureus infections in non-CF patients. Topical treatment strategies successfully eradicate nasal S. aureus carriage, thereby decreasing S. aureus infection. A prospective longitudinal multicenter study was conducted to assess whether nasal carriage represents a risk factor for S. aureus colonization of the oropharynx in young CF patients. Cross-sectional analysis revealed a significantly higher prevalence of S. aureus-positive nasal (28/80 [35%] versus 20/109 [18%]; P < 0.01) and oropharyngeal (35/80 [44%] versus 20/109 [18%]; P < 0.001) cultures in children with CF compared to a control group. The first site of S. aureus detection was the nose in 6 patients and the oropharynx in 14 patients, respectively. Longitudinal analysis demonstrated a significantly higher S. aureus prevalence (61/62 [98%] versus 47/62 [76%]; P < 0.001) and persistence (46/62 [74%] versus 31/62 [50%]; P < 0.01) in the oropharynx than in the nose. In CF patients, the oropharynx, and not the nose, was the predominant site of S. aureus infection and persistence. Hence, it is unlikely that CF patients will benefit from topical treatment strategies to eradicate nasal carriage.     

Rehabilitation bei Kindern und Jugendlichen mit Diabetes mellitus

Background

Medical rehabilitation plays a special role in the treatment of children and adolescents with diabetes mellitus: services which are difficult to implement in an out-patient or an acute in-patient setting can be provided. The study analyzed changes over a period of 12 years.

Methods

In a monocentric, retrospective cross-sectional analysis, all (n = 2001) children and adolescents with diabetes (52% girls, age 12.6 ± 4.9 years) who were admitted to a specialist clinic for rehabilitation during the period 01/2004–12/2016 were examined.

Results

The duration of medical rehabilitation was 27.3 ± 6.1 days. In all, 1980 of 2001 (98.9%) children and adolescents had type 1 diabetes, while 21 of 2001 (1.1%) had type 2 diabetes. Mean HbA1c was 7.87 ± 1.47%. Overall, 1897 of 2001 (95%) patients had an intensified insulin therapy, of which 633 (32%) used insulin pumps (CSII). They injected 0.86 ± 0.47?I.?U. insulin/kg body weight/day and performed 37.6 ± 11.4 blood glucose self-tests/week. The number of patients who participated in medical rehabilitation decreased: In 2016 it was 68% lower than in 2007, the year of the highest number of patients (p < 0.05). Parameters of metabolic control hardly changed. The proportion of patients with CSII increased (p < 0.05). In particular, young children used CSII more frequently (59% in <4 year olds vs 24% in 16–17 year olds, p < 0.05). Changes also occurred in cultural status: The percentage of patients from German families decreased (p < 0.05); the proportion of patients from mixed-cultural families increased (p < 0.05). The number of patients living together with both parents also decreased (p < 0.05 for the tendency); the number of patients living with single parents increased (p < 0.05 for the tendency). In young children, HbA1c values were the lowest. From the beginning of puberty (about 10 years), HbA1c increased (8.5 ± 1.9% in 16–17 year olds). There were no correlations/associations between metabolic control and the incidences of hypoglycemia/ketoacidoses.

Conclusions

There has been a change in medical rehabilitation: The number of patients has decreased, the proportion of patients using CSII has increased, the number of patients living with single parents and the percentage of patients from a culturally mixed families has also increased. Thus, there are new challenges in medical rehabilitation.