The Non-phosphorylating Glyceraldehyde-3-Phosphate Dehydrogenase GapN Is a Potential New Drug Target in Streptococcus pyogenes.

The strict human pathogen Streptococcus pyogenes causes infections of varying severity, ranging from self-limiting suppurative infections to life-threatening diseases like necrotizing fasciitis or streptococcal toxic shock syndrome. Here, we show that the non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase GapN is an essential enzyme for S. pyogenes. GapN converts glyceraldehyde 3-phosphate into 3-phosphoglycerate coupled to the reduction of NADP to NADPH. The knock-down of gapN by antisense peptide nucleic acids (asPNA) significantly reduces viable bacterial counts of S. pyogenes laboratory and macrolide-resistant clinical strains in vitro. As S. pyogenes lacks the oxidative part of the pentose phosphate pathway, GapN appears to be the major NADPH source for the bacterium. Accordingly, other streptococci that carry a complete pentose phosphate pathway are not prone to asPNA-based gapN knock-down. Determination of the crystal structure of the S. pyogenes GapN apo-enzyme revealed an unusual cis-peptide in proximity to the catalytic binding site. Furthermore, using a structural modeling approach, we correctly predicted competitive inhibition of S. pyogenes GapN by erythrose 4-phosphate, indicating that our structural model can be used for in silico screening of specific GapN inhibitors. In conclusion, the data provided here reveal that GapN is a potential target for antimicrobial substances that selectively kill S. pyogenes and other streptococci that lack the oxidative part of the pentose phosphate pathway.

Accumulating Comorbidities May Promote Increasing Severity of Obstructive Sleep Apnea with Aging in Males but Not in Females.

Evidence suggests an increasing apnea−hypopnea index (AHI) with aging. However, the effect of aging on sleep-related metrics, especially AHI, has been less frequently investigated within different gender-specific subpopulations by taking prominent confounding factors, e.g., obstructive sleep apnea (OSA)-related comorbidities and body mass index (BMI) into account. Therefore, we retrospectively analyzed 186 first-time polysomnographic (PSG) recordings and medical files of all patients presented to a tertiary university sleep center during a 1-year period. Six groups were formed based on age (over vs. under 55 years) and gender: PSG-related parameters (AHI, apnea-index, and hypopnea-index) were significantly higher in the older mixed-gender cohort (p = 0.0001, p = 0.0011, and p = 0.0015, respectively), and the older female cohort (p = 0.0005, p = 0.0027, and p = 0.001, respectively). Within the older male cohort, the AHI and apnea-index were significantly higher (p = 0.0067, and p = 0.0135, respectively). Inter-group comparison of the BMI showed no significant difference in any subpopulation. Within the older male cohort there were significantly more patients with arterial hypertension, diabetes mellitus, cardiovascular diseases, and chronic mental health disorders (p < 0.0001, p = 0.001, p = 0.0181, and p = 0.0454, respectively). Contrarily, within the female subpopulation there were no significant differences for the aforementioned comorbidities. In conclusion, all investigated sleep PSG-parameters increased among the older subpopulations. We suggest that Osa severity may increase with age due to the increasing accumulation of comorbidities in males, but not in females.

[Impact of the COVID-19 pandemic on speech therapy for children with Speech and Language Disorders]. / Auswirkungen der COVID-19-Pandemie auf die logopädische Therapie von Kindern mit einer Sprachentwicklungsstörung.

OBJECTIVE: In December 2019, the COVID-19 pandemic began to spread around the world and caused massive restrictions in our daily life. Many educational facilities and practices delivering speech therapy were temporally closed (so-called lockdown). Children with a speech and language disorder were forced to pause their therapy. The aim of this study was to describe if and how speech therapy was delivered during lockdown and what psychological burden was associated to affected parents. MATERIAL AND METHODS: Parents of children with a speech and language disorder were asked about their child´s therapy during lockdown and about their fears and worries associated with it. RESULTS: For 17 patients speech therapy was paused during lockdown while 20 patients could continue their therapy. Children speaking a language other than German had a higher risk for having their therapy paused during lockdown (Odds ratio = 5.11, with 95 % confidence interval = 1.09-32.54). Parents whose children did not receive speech therapy during lockdown were more worried about their child's development. CONCLUSIONS: There is no common concept on how speech therapy can be delivered safely during lockdown. Possible barriers to healthcare might be more pronounced during the pandemic and parents experience a high psychosocial burden.

[Obstructive sleep apnea syndrome in children]. / Kindliches obstruktives Schlafapnoesyndrom.

Pediatric obstructive sleep apnea syndrome (OSAS) has a high prevalence in the general population. Risk factors are adenotonsillar hyperplasia, preterm birth, obesity, and craniofacial dysmorphia. A special feature of pediatric OSAS is that it can manifest in behavioral problems. These patients also have an increased risk of perioperative anesthesiologic complications. Diagnostic and therapeutic options should be defined individually using the "Snoring in childhood" algorithm of the German Sleep Research and Sleep Medicine Society (DGSM). Diagnosis based on polysomnography (PSG) is reserved for specialized pediatric sleep centers. The most common surgical treatment for pediatric OSAS is adenoidectomy with tonsillotomy. Positive airway pressure (PAP) therapy in children is only indicated in individual cases. Monitoring of treatment success is important after OSAS therapy.