Correction to: Incidental diagnosis of tuberous sclerosis complex by exome sequencing in three families with subclinical findings.

The published online version contain mistake in the author list. Instead of "A.M.Ilyas" it should have been "M.Ilyas ".

Incidental diagnosis of tuberous sclerosis complex by exome sequencing in three families with subclinical findings.

Tuberous sclerosis complex (TSC) is an autosomal-dominant neurocutaneous disorder characterized by lesions and benign tumors in multiple organ systems including the brain, skin, heart, eyes, kidneys, and lungs. The phenotype is highly variable, although penetrance is reportedly complete. We report the molecular diagnosis of TSC in individuals exhibiting extreme intra-familial variability, including the incidental diagnosis of asymptomatic family members. Exome sequencing was performed in three families, with probands referred for epilepsy, autism, and absent speech (Family 1); epileptic spasms (Family 2); and connective tissue disorders (Family 3.) Pathogenic variants in TSC1 or TSC2 were identified in nine individuals, including relatives with limited or no medical concerns at the time of testing. Of the nine individuals reported here, six had post-diagnosis examinations and three met clinical diagnostic criteria for TSC. One did not meet clinical criteria for a possible or definite diagnosis of TSC, and two had only a possible clinical diagnosis following post-diagnosis workup. These individuals as well as their mothers demonstrated limited features that would not raise concern for TSC in the absence of molecular results. In addition, three individuals exhibited epilepsy with normal brain MRIs, and two without seizures or intellectual disability had MRI findings fulfilling major criteria for TSC highlighting the difficulty providers face when relying on clinical criteria to guide genetic testing. Given the importance of a timely TSC diagnosis for clinical management, such cases demonstrate a potential benefit for clinical criteria to include seizures and an unbiased molecular approach to genetic testing.

Keeping our heads above water: A systematic review of fatal drowning in South Africa

Background. Drowning is defined as the process of experiencing respiratory impairment from submersion/immersion in liquid, and can have one of three outcomes ­ no morbidity, morbidity or mortality. The World Health Organization African region accounts for approximately 20% of global drowning, with a drowning mortality rate of 13.1 per 100 000 population. The strategic implementation of intervention programmes driven by evidence-based decisions is of prime importance in resource-limited settings such as South Africa (SA).Objective. To review the available epidemiological data on fatal drowning in SA in order to identify gaps in the current knowledge base and priority intervention areas. Methods. A systematic review of published literature was conducted to review the available epidemiological data describing fatal drowning in SA. In addition, an internet search for grey literature, including technical reports, describing SA fatal drowning epidemiology was conducted.Results. A total of 13 published research articles and 27 reports obtained through a grey literature search met the inclusion and exclusion criteria. These 40 articles and reports covered data collection periods between 1995 and 2016, and were largely focused on urban settings. The fatal drowning burden in SA is stable at approximately 3.0 per 100 000 population, but is increasing as a proportion of all non-natural deaths. Drowning mortality rates are high in children aged <15 years, particularly in those aged <5. Conclusions. This review suggests that SA drowning prevention initiatives are currently confined to the early stages of an effective injury prevention strategy. The distribution of mortality across age groups and drowning location differs substantially between urban centres and provinces. There is therefore a need for detailed drowning surveillance to monitor national trends and identify risk factors in all SA communities

Keeping our heads above water: A systematic review of fatal drowning in South Africa.

BACKGROUND: Drowning is defined as the process of experiencing respiratory impairment from submersion/immersion in liquid, and can have one of three outcomes - no morbidity, morbidity or mortality. The World Health Organization African region accounts for approximately 20% of global drowning, with a drowning mortality rate of 13.1 per 100 000 population. The strategic implementation of intervention programmes driven by evidence-based decisions is of prime importance in resource-limited settings such as South Africa (SA). OBJECTIVE: To review the available epidemiological data on fatal drowning in SA in order to identify gaps in the current knowledge base and priority intervention areas. METHODS: A systematic review of published literature was conducted to review the available epidemiological data describing fatal drowning in SA. In addition, an internet search for grey literature, including technical reports, describing SA fatal drowning epidemiology was conducted. RESULTS: A total of 13 published research articles and 27 reports obtained through a grey literature search met the inclusion and exclusion criteria. These 40 articles and reports covered data collection periods between 1995 and 2016, and were largely focused on urban settings. The fatal drowning burden in SA is stable at approximately 3.0 per 100 000 population, but is increasing as a proportion of all non-natural deaths. Drowning mortality rates are high in children aged <15 years, particularly in those aged <5. CONCLUSIONS: This review suggests that SA drowning prevention initiatives are currently confined to the early stages of an effective injury prevention strategy. The distribution of mortality across age groups and drowning location differs substantially between urban centres and provinces. There is therefore a need for detailed drowning surveillance to monitor national trends and identify risk factors in all SA communities.

Dissecting the role of TRPV1 in detecting multiple trigeminal irritants in three behavioral assays for sensory irritation.

Polymodal neurons of the trigeminal nerve innervate the nasal cavity, nasopharynx, oral cavity and cornea. Trigeminal nociceptive fibers express a diverse collection of receptors and are stimulated by a wide variety of chemicals. However, the mechanism of stimulation is known only for relatively few of these compounds. Capsaicin, for example, activates transient receptor potential vanilloid 1 (TRPV1) channels. In the present study, wildtype (C57Bl/6J) and TRPV1 knockout mice were tested in three behavioral assays for irritation to determine if TRPV1 is necessary to detect trigeminal irritants in addition to capsaicin. In one assay mice were presented with a chemical via a cotton swab and their response scored on a 5 level scale. In another assay, a modified two bottle preference test, which avoids the confound of mixing irritants with the animal's drinking water, was used to assess aversion. In the final assay, an air dilution olfactometer was used to administer volatile compounds to mice restrained in a double-chambered plethysmograph where respiratory reflexes were monitored. TRPV1 knockouts showed deficiencies in the detection of benzaldehyde, cyclohexanone and eugenol in at least one assay. However, cyclohexanone was the only substance tested that appears to act solely through TRPV1.

Flammable gas cloud build up in a ventilated enclosure.

Ventilation is frequently used as a means for preventing the build up of flammable or toxic gases in enclosed spaces. The effectiveness of the ventilation often has to be considered as part of a safety case or risk assessment. In this paper methods for assessing ventilation effectiveness for hazardous area classification are examined. The analysis uses data produced from Computational Fluid Dynamics (CFD) simulations of low-pressure jet releases of flammable gas in a ventilated enclosure. The CFD model is validated against experimental measurements of gas releases in a ventilation-controlled test chamber. Good agreement is found between the model predictions and the experimental data. Analysis of the CFD results shows that the flammable gas cloud volume resulting from a leak is largely dependent on the mass release rate of flammable gas and the ventilation rate of the enclosure. The effectiveness of the ventilation for preventing the build up of flammable gas can therefore be assessed by considering the average gas concentration at the enclosure outlet(s). It is found that the ventilation rate of the enclosure provides a more useful measure of ventilation effectiveness than considering the enclosure air change rate.

No association of the ACTN3 gene R577X polymorphism with endurance performance in Ironman Triathlons.

Alpha-actinins are major structural components of the Z-discs in skeletal muscle. Alpha-actinin 3 is encoded by the ACTN3 gene and is expressed only in type II muscle fibres. Homozygosity for the nonsense mutation, 577X, within ACTN3 results in deficiency of alpha-actinin-3 but does not result in an abnormal muscular phenotype. Previous research has found an association of the 577R allele with sprinting and/or power performance. It has also been suggested that the 577X allele may confer an advantage during endurance events. Four hundred and fifty seven Caucasian male triathletes who completed either the 2000 and/or 2001 226 km South African Ironman Triathlons, and 143 Caucasian controls, were genotyped for the R577X mutation within the ACTN3 gene. There were no significant differences in either the genotype (P = 0.486) or allele (P = 0.375) frequencies within the fastest, middle of the field or slowest Caucasian male finishers and the control population. In conclusion, the R577X polymorphism within the ACTN3 gene was not associated with ultra-endurance performance in the 2000 and 2001 South African Ironman Triathlons.

Characteristics of pesticide pyrotechnic smoke devices.

Pesticide smoke generating products are widely used by amateurs and professionals but there is little published information available about their burn and deposition characteristics to enable the risks associated with using these devices to be assessed. This paper investigates their burn characteristics, deposition patterns, pesticide air concentrations and potential exposure to operators. Thirteen firings were carried out in different spaces with different ventilation conditions. Three types of devices were investigated: dicloran, permethrin and red dye. Pesticide air concentrations increased after firing, reaching a maximum determined by the room volume in approximately 10 min and decreasing exponentially as a result of ventilation and deposition. Ejected pesticide was present in the aerosol phase but there were only occasional traces of vapour. Settlement of pesticide was affected by surface orientation, height, sampling material and the pesticide-to-space volume ratio. The manufacturer's recommended treatment period for dicloran of 4 h followed by half an hour of ventilation may be insufficient to reduce pesticide to safe levels for re-entry under very calm conditions.

Functional analysis of the human galactose-1-phosphate uridyltransferase promoter in Duarte and LA variant galactosemia.

Human galactose-1-phosphate uridyltransferase (hGALT) is an evolutionarily conserved enzyme central to D-galactose metabolism. The impairment of hGALT causes galactosemia. One missense mutation, an aspartate to asparagine substitution at amino acid 314 (N314D), impairs 50% activity in the homozygous state in some patients but gives near normal activity in others. The former condition is called Duarte (D) and the latter, Los Angeles (LA). The D allele is linked to hGALT polymorphisms including a deletion 5'to the translation start site (-119 to -116delGTCA), g1391G --> A and g1105G --> C. The LA allele is linked to a g1721C --> T transition. To investigate possible mechanisms for differences in hGALT activity between the D and LA alleles, we sequenced 3951 nucleotides of genomic DNA 5' to the hGALT translation start site. Using a dual-luciferase reporter system to express deletion constructs of the hGALT promoter, we noted both positive and negative regulatory regions. Two putative positive regulatory domains overlap with the naturally occurring -119 to -116delGTCA linked to Duarte. One is an E-box motif (CACGTG) at -117 to -112 bp. The second is an AP-1 motif (TCAGTCAG) at -124 to -119 bp. The delGTCA mutation confers reduced luciferase activity to transfected cell lines derived from human ovarian and liver neoplasms. Additionally, human lymphoblasts derived from patients with the Duarte allele have reduced GALT mRNA. We conclude that the human GALT gene is regulated in the first -165 bp of its promoter region by positive regulators of GALT gene expression. The -119 to -116delGTCA reduces hGALT transcription resulting in reduced GALT activity in the Duarte allele.

Endoscopically assisted facial suspension for treatment of facial palsy.

Static suspension remains an option for certain patients with facial paralysis. Endoscopically assisted facial suspension obviates the need for a counter-incision at the oral commissure to distally inset the fascia lata graft as described in the standard technique. The endoscopic technique is simple, allows secure placement of perioral fascial strips, and can be performed as an outpatient.

Arterial vascular anatomy of the umbilicus.

The rare occurrence of umbilical necrosis after performance of a transverse rectus abdominis muscle (TRAM) flap prompted this investigation into the specific arterial anatomy of the umbilicus using multiple anatomic techniques. Sixteen fresh cadavers were studied by using dissection of blue latex-injected specimens, radiography of barium latex-injected specimens, and selective ink injection of individual perforators. It was discovered that the umbilicus receives arterial inflow by means of three distinct deep sources in addition to the subdermal plexus. These deep sources are (1) the right and left deep inferior epigastric arteries that each give off several small branches, and a large ascending branch, which courses between the muscle and the posterior rectus sheath passing directly to the umbilicus; (2) the ligamentum teres hepaticum; and (3) the median umbilical ligament. The clinical implications of this study are that the umbilicus should have robust arterial inflow if only one rectus muscle is removed, such as during a unilateral TRAM flap, because the contralateral side should still provide large direct vessels from the deep inferior epigastric arteries to the umbilicus. During bilateral TRAM elevation, all of the large arterial sources are removed from the umbilical inflow and circulation must depend on small vessels from the ligamentum teres and median umbilical ligament. Care should be taken in this latter clinical situation to preserve these sources of blood flow during umbilical flap creation.

Percutaneous diagnostic peritoneal lavage using a Veress needle versus an open technique: a prospective randomized trial.

OBJECTIVE: To prospectively compare the speed, sensitivity, complications, and technical failures of percutaneous diagnostic peritoneal lavage (DPL) using a Veress needle versus open DPL. METHODS: One hundred seventy-six blunt trauma patients requiring DPL were prospectively randomized to undergo either open DPL using a standard technique or percutaneous DPL using an 18-gauge Veress needle to penetrate the peritoneal cavity, with the lavage catheter then being inserted over a guide wire. RESULTS: Mean time to successful placement of the lavage catheter for the percutaneous Veress needle technique was 2.73 minutes versus 7.28 minutes for the open DPL technique (p < 0.001). Sixteen percent of open lavage procedures took more than 11 minutes; the majority (60%) of Veress needle lavage procedures took less than 2 minutes. There were no false-negative findings in either group, and there was one false-positive result in each group. A wound infection after an open DPL was the only complication. Poor return of lavage fluid (<200 mL) accounted for most technical failures; this was more prevalent with the percutaneous method (11.2%) than with the open technique (3.8%) (p < 0.05). CONCLUSION: The percutaneous DPL method using a Veress needle is significantly faster than the open DPL method. The Veress needle lavage was as safe and as sensitive as the open lavage; however, technical failure occurred more frequently with the Veress needle lavage than with the open DPL.

Transantral endoscopic orbital floor exploration: a cadaver and clinical study.

A cadaver and clinical study was performed to determine the value of transantral endoscopy in diagnosis and treatment of orbital floor fractures. Six fresh cadaver heads were dissected using a 30 degree, 4-mm endoscope through a 1 cm2 antrotomy. In the cadaver, the orbital floor and the course of the infraorbital nerve were easily identified. The infraorbital nerve serves as a reference point for evaluation of fracture size; three zones of the floor are described that are oriented relative to the infraorbital nerve. In the clinical study, nine patients with orbital floor fracture initially underwent endoscopy at the time of fracture repair: three patients had comminuted zygomatico-orbital fractures, five had monofragmented tetrapod fractures, and one had an isolated orbital blowout fracture. Endoscopic dissection of the orbital fractures revealed seven fractures with an area > 2 cm2 and two fractures with an area of < 2 cm2. The isolated orbital floor blowout fracture had entrapped periorbital tissue, which was completely reduced endoscopically. A separate patient with a < 2 cm2 displaced fracture also had stable endoscopic reduction. In the remaining seven patients, the endoscopic technique assisted with the floor reconstruction by identifying the precise fracture configuration as well as identifying the stable posterior ledge of the orbital floor fracture. There have been no complications in any of our patients to date. We conclude: (1) Transantral orbital floor exploration allows precise determination of orbital floor fracture size, location, and the presence of entrapped periorbita. The information obtained through endoscopic techniques may be used to select patients who would not benefit from lid approaches to the orbital floor and may possibly eliminate nontherapeutic exploration. (2) Transantral endoscopic orbital floor exploration assists the reduction of complex orbital floor fractures and allows precise identification of the posterior shelf for implant placement. (3) Transantral endoscopic techniques can completely reduce entrapped periorbital tissue caught in a trapdoor type of fracture.

Arterial anatomy of the oral cavity: an analysis of vascular territories.

Knowledge of the specific cutaneous or surface regions supplied by constant named arterial sources has allowed for increasing clinical application of flap transfers of tissue. Despite the routine use of intraoral flaps for reconstruction of congenital or acquired defects of the oral cavity and pharynx, no previous investigation has centered on understanding the surface or mucosal arterial territories of the oral cavity. In a cadaver study, six mucosal territories of the intraoral cavity were defined using selective ink and lead oxide injections through named arteries. The anatomical boundaries of these territories are predictable and constant in location for different cadavers. The six contiguous territories are based on the buccal, labial, inferior alveolar, ascending palatine, ascending pharyngeal, and lingual arteries. This study supports the safe vascular basis of existing clinical procedures of the intraoral cavity and may have implications for the design of new intraoral reconstructive procedures.

Reconstruction of the toddler diaphragm in severe anterolateral congenital diaphragmatic hernia with the reverse latissimus dorsi flap.

The management of infants with severe congenital diaphragmatic hernia (CDH) continues to evolve. When a prosthetic patch is placed in the neonatal period for pleuroperitoneal separation, it ultimately will require a subsequent reconstruction for progressive pulmonary or abdominal symptomatology. The reverse latissimus dorsi (RLD) flap has been used for reconstruction in only several reports in the last 12 years. In this paper, a patient with severe anterolateral CDH is reconstructed with the RLD flap on an elective basis at 2 years of age. Elective repair was performed for the particular indication of chest wall restriction imposed by the nonpliable Gore-Tex patch. In this case, use of the RLD flap alone without the use of synthetic mesh has resulted in satisfactory results with 17 months of follow up.

Bregmatic masses in children.

Bregmatic masses often present a challenging diagnostic dilemma. We present two illustrative cases to demonstrate this clinical problem and present our recommendations for evaluation and treatment.

Bregmatic epidermoid inclusion cyst eroding both calvarial tables.

Dermoid and epidermoid cysts are uncommon masses in the head and neck region of children. Although the most common location of inclusion cysts in the head and neck is the bregma, masses in this region must be differentiated from midline hemangiomas, lipomas, hematomas, or encephaloceles. Inclusion cysts should be considered in the differential diagnosis of all midline cystic lesions in infants, because, if left untreated, it may lead to devastating complications. We present the case of a slowly enlarging midline mass in a female infant to illustrate the potential for serious sequelae from inclusion cysts.

Air movement around a worker in a low-speed flow field.

A knowledge of the air movement around a worker in a low-speed airflow is important in a number of areas: containment testing of fume cupboards; testing of personal dust samplers; testing of LEV effectiveness; and measurement of worker exposure. Measurements of velocity vectors around the upper torsos of manikins and a human in low-speed airflows have been made using a laser Doppler anemometer. Both heated and unheated manikins, as well as a 'breathing' manikin were used. The results show that quite distinctive flow patterns develop with heated and unheated bodies. Comparison of the flows around two- and three-dimensional manikins with that around a human shows that only a three-dimensional heated manikin gives good results. The unheated breathing manikin gave results which were unrepresentative of the real situation. A suitable manikin for use in sampling or testing in low-speed airflows would have a heated, rounded, three-dimensional body of reasonably human dimensions and would be non-breathing and clothed.