TUBB3 E410K syndrome: Case report and review of the clinical spectrum of TUBB3 mutations

The tubulinopathies refer to a wide range of brain malformations caused by mutations in one of the seven genes encoding different tubulin's isotypes. The β‐tubulin isotype III (TUBB3) gene has a primary function in nervous system development and axon generation and maintenance, due to its neuron‐specific expression pattern. A recurrent heterozygous mutation, c.1228G > A; p.E410K, in TUBB3 gene is responsible of a rare disorder clinically characterized by congenital fibrosis of the extraocular muscle type 3 (CFEOM3), intellectual disability and a wide range of neurological and endocrine abnormalities. Other mutations have been described spanning the entire gene and genotype–phenotype correlations have been proposed. We report on a 3‐year‐old boy in whom clinical exome sequencing allowed to identify a de novo TUBB3 E410K mutation as the molecular cause underlying a complex phenotype characterized by a severe bilateral palpebral ptosis refractory to eye surgery, psychomotor delay, absent speech, hypogonadism, celiac disease, and cyclic vomiting. Brain MRI revealed thinning of the corpus callosum with no evidence of malformation cortical dysplasia. We reviewed available records of patients with TUBB3 E410K mutation and compared their phenotype with the clinical outcome of patients with other mutations in TUBB3 gene. The present study confirms that TUBB3 E410K results in a clinically recognizable phenotype, unassociated to the distinct cortical dysplasia caused by other mutations in the same gene. Early molecular characterization of TUBB3 E410K syndrome is critical for targeted genetic counseling and prompt prospective care in term of neurological, ophthalmological, endocrine, and gastrointestinal follow‐up.     

Dissociation of conditioned locomotion and Fos induction in response to stimuli formerly paired with cocaine

A discrete stimulus (flashing light) was paired with cocaine (20 mg/kg) to induce conditioned locomotion. To identify brain regions activated during this response, Fos was measured with immunohistochemistry. Although paired subjects displayed robust conditioned locomotion, Fos was not increased in any limbic brain regions analyzed. In contrast, pairing of cocaine with generalized contextual cues (whole room) produced conditioned locomotion and Fos activation in the prelimbic portion of prefrontal cortex and the nucleus accumbens core. These results suggest that the pattern of neuronal activation during cocaine-conditioned activity differs depending on whether a discrete or contextual stimulus is used as a conditioned stimulus. The possibility that expectancy and frustrative nonreward contribute to Fos expression in rats conditioned to contextual cues is discussed.     

Production of IL-12, IL-23 and IL-27p28 by bone marrow-derived conventional dendritic cells rather than macrophages after LPS/TLR4-dependent induction by Salmonella Enteritidis

Induction of the interleukin-12 (IL-12) cytokine family comprising IL-12, IL-23, IL-27, and IL-12p40 by intracellular pathogens is required for orchestration of cell-mediated immune responses. Macrophages (MΦ) have been shown to be a source of IL-12 following TLR4-dependent activation by Salmonella (S.). In this study another antigen-presenting cell type, the conventional dendritic cell (cDC), was analyzed and its cytokine responses compared with those of MΦ. We generated bone marrow-derived conventional dendritic cells (BMDC) and macrophages (BMMΦ) by incubating murine bone marrow cells with supernatants containing granulocyte/macrophage colony-stimulating factor (GM-CSF) or macrophage colony-stimulating factor (M-CSF), respectively. Stimulation of BMDC and BMMΦ with S. enterica serovar Enteritidis (SE) or LPS resulted in the release of IL-12 and IL-23 by BMDC but not by BMMΦ. Furthermore, BMDC secreted approx. 20-fold more IL-12p40 and IL-27p28 than BMMΦ. However, BMDC and BMMΦ produced similar levels of IL-10. Using BMDC originating from wild-type (wt), TLR2^def and TLR4^def mice, we show that in BMDC the induction of IL-12, IL-23, and IL-27p28 by SE is dependent on TLR4, whereas low-level production of p40 is also mediated by pattern recognition receptors (PRR) other than TLR4. Interestingly, LPS- and SE-provoked responses of BMDC were remarkably similar indicating that LPS is the primary danger molecule of SE. Taken together, our results point to cDC rather than MΦ as the major producers of the IL-12 family members during in vitro infection with SE. The mechanisms of recognition of SE, however, appear to be the same for cDC and MΦ     

Highly Pathogenic Avian Influenza A(H5N8) Virus Spread by Short- and Long-Range Transmission,France, 2016–17

We detected 3 genotypes of highly pathogenic avian influenza A(H5N8) virus in France during winter 2016–17. Genotype A viruses caused dramatic economic losses in the domestic duck farm industry in southwestern France. Our phylogenetic analysis suggests that genotype A viruses formed 5 distinct geographic clusters in southwestern France. In some clusters, local secondary transmission might have been started by a single introduction. The intensity of the viral spread seems to correspond to the density of duck holdings in each production area. To avoid the introduction of disease into an unaffected area, it is crucial that authorities limit the movements of potentially infected birds.     

Association of photobiomodulation therapy (PBMT) and exercises programs in pain and functional capacity of patients with knee osteoarthritis (KOA): a systematic review of randomized trials

Lasers in Medical Science - Knee osteoarthritis (KOA) is a common degenerative disease in which several treatments and treatment associations have been investigated. This review analyzed the...     

Quality of life outcomes after minimally invasive repair of pectus excavatum utilizing a new set of metallic bars and stabilizers

Background/PurposeThe aim of the study was to evaluate the postoperative quality of life (QoL) of patients who underwent minimally invasive repair of pectus excavatum (MIRPE) with a newly designed bar and bar stabilizers.MethodsWe conducted a prospective randomized study in which patients were operated either with standard perpendicular stabilizers (control group) or with the newly designed oblique stabilizers (intervention group). All patients were evaluated 6 months after the operation with the Pectus Excavatum Evaluation Questionnaire (PEEQ).ResultsThere were 16 patients in the control group and 14 in the intervention group. Mean age was 17 (SD: 3.3, range 14–27) years. There were no demographic differences between groups. Two patients in the control group and one in the intervention group were repaired with two bars instead of one. There was one reoperation in each group. There was a significant difference between the pre- and postoperative scores, in both groups, in the patient body image domain (control group: 9.5 to 3; p < 0.01; intervention group 10 to 3; p < 0.01), as well as in the psychosocial domain (control group: 13.5 to 24, p < 0.01; intervention group: 15 to 24, p < 0.01). With regards to the patients' perception of physical difficulties before and after MIRPE, the difference between pre- and postoperative scores was greater in the intervention group (8 to 12, p < 0.01) than in the control group (10 to 11, p = 0.04). The mean length of stay was 4.5 and 5 days in the intervention group and the control group, respectively.ConclusionOur study showed that patients who underwent MIRPE with the newly designed bars and stabilizers had non-inferior outcomes than patients reported in the literature who underwent MIRPE with standard bars and stabilizers. We found slightly better outcomes in patients in the intervention group compared to the control group, but larger studies will be needed to confirm if those differences are statistically significant.Level of evidenceII     

Gel tópico de amitriptilina al 2% y ketamina al 0,5% para el tratamiento de la eritromelalgia: reporte de un caso con respuesta positiva al dolor

Erythromelalgia (EM) is a rare autosomal dominant neuropathy characterized by the combination of severe burning pain and erythematous warm extremities. Chronic pain control is most often unsuccessful and a completely effective therapy is yet to be identified. Recent studies have reported significant improvements in pain management using a combination of amitriptyline and ketamine in a topical formulation. We describe a 1-year follow-up pain control success case of a male patient with EM, proposed for topical use of a 2% Amitriptyline and 0.5% Ketamine gel.     

Vascular anatomy of the first metatarsal bone and surgical implications according to the severity of hallux valgus deformity: A cadaveric study

BackgroundVascular injury after hallux valgus surgery is a rare condition but serious complications can ensue.MethodsWe performed an anatomical study using 26 cadaveric lower extremities. We enhanced first metatarsal bone’s (FMB) vascularization by injecting latex. Each specimen was classified according to the severity of hallux valgus deformity (HVD). Then we measured two distances: one between the first tarsometatarsal joint (FTMJ) to the first dorsal branch’s origin, the other between the first metatarsophalangeal joint (MTP) to the dorsal plexus’s origin.ResultsThe distance between the FTMJ and the first dorsal branch to the FMB ranges from 10 mm in normal feet to 15 mm in severe deformed feet. The distance between the MTP and the dorsal plexus’ origin ranges from 20 mm in normal feet to 25 mm in severe deformed feet.ConclusionsUnderstanding the foot’s vascular anatomy has allowed us to adapt surgical landmarks to the severity of the HVD and to avoid post-operative complications.     

Narrative review of prostate cancer grading systems: will the Gleason scores be replaced by the Grade Groups?

The Gleason grading system, proposed by Dr. Donald F. Gleason in 1966, is one of the most important prognostic factors in men with prostate cancer (PCa). At consensus conferences held in 2005 and 2014, organized by the International Society of Urological Pathology (ISUP), the system was modified to reflect the current diagnostic and therapeutic approaches. In particular, in the 2014 Conference, it was recognized that there were weaknesses with the original and the 2005 ISUP modified Gleason systems. Based on the results of a research conducted by Prof. JI Epstein and his group, a new grading system was proposed by the ISUP in order to address some of such deficiencies: i.e., the five distinct Grade Groups (GGs). Since 2014, results of studies have been published by different groups and societies, including the Genitourinary Pathology Society (GUPS), giving additional support to the prognostic role of the architectural Gleason patterns and, in particular, of the GGs. A revised GG system, taking into account the percentage of Gleason pattern (GP) 4, cribriform and intraductal carcinoma, tertiary GP 5, and reactive stroma grade, has shown to have some advantages, however not ready for adoption in the current practice. The aim of this contribution was to review the major updates and recommendations regarding the GPs and GSs, as well as the GGs, trying to give an answer to the following questions: “How has the grade group system been used in the routine?” and “will the Gleason scoring system be replace by the grade groups?” We also discussed the potential implementation in the future of molecular pathology and artificial intelligence in grading to further define risk groups in patients with PCa.     

Validation of a screening test for alcohol use,the Russian Federation

ObjectiveTo validate a Russian-language version of the World Health Organization’s Alcohol Use Disorders Identification Test (AUDIT).MethodsWe invited 2173 patients from 21 rural and urban primary health-care centres in nine Russian regions to participate in the study (143 declined and eight were excluded). In a standardized interview, patients who had consumed alcohol in the past 12 months provided information on their sociodemographic characteristics and completed the Russian AUDIT, the Kessler Psychological Distress Scale and the Composite International Diagnostic Interview to identify problem drinking and alcohol use disorders. We assessed the feasibility of administering the test, its internal consistency and its ability to predict hazardous drinking and alcohol use disorders in primary health care in the Russian Federation.FindingsOf the 2022 patients included in the study, 1497 were current drinkers with Russian AUDIT scores. The test was internally consistent with good psychometric properties (Cronbach’s α : 0.842) and accurately predicted alcohol use disorders and other outcomes (area under the curve > 75%). A three-item short form of the test correlated well with the full instrument and had similar predictive power (area under the curve > 80%). We determined sex-specific thresholds for all outcomes, as non-specific thresholds resulted in few women being identified.ConclusionWith the validated Russian AUDIT, there is no longer a barrier to introducing screening and brief interventions into primary health care in the Russian Federation to supplement successful alcohol control policies.