Prevalence of neural tube defect in southern Thailand: a population-based survey during 2009–2012

Background

Neural tube defects (NTDs) are a group of congenital malformation of the central nervous system that leads to permanent physical disability and requires lifelong treatment. In Thailand, there have been three published articles on NTDs, all hospital-based studies, which found prevalence of NTDs of 4.8–6.7 per 10,000 live births.

Objective

It was our purpose with this study to determine the prevalence and type of NTDs in southern Thailand through a population-based survey.

Method

Data were obtained through the population-based surveillance during 2009–2012 in three provinces (Songkhla, Phatthalung, Trang) in southern Thailand. Entries in the birth defects registry included all live births, all stillbirths after 24-week gestational age, and termination of pregnancy following the prenatal diagnosis at any gestational age of all congenital anomalies.

Results

During 2009–2012, 148,759 births were registered in the three provinces. Twenty-eight NTD cases were identified, giving an average of 1.88 per 10,000 births (95 % CI 1.20–2.51): 12 cases with anencephaly (42.8 %), 5 with occipital encephalocele (17.9 %), and 11 with myelomeningocele (39.3 %). The birth prevalence per 10,000 births of anencephaly, encephalocele, and myelomeningocele were 0.81, 0.33, and 0.74, respectively. Sixteen (57 %) were detected in live births, and 12 (43 %) were detected by prenatal diagnosis which later resulted in termination of pregnancy.

Conclusions

The prevalence of NTDs based on the population-based study in southern Thailand was low. About 40 % of NTD cases were detected prenatally and later terminated. Hence, examining only registry live births will result in an inaccurately low NTD prevalence rate.     

Insulin resistance in subjects with a history of thyrotoxic periodic paralysis (TPP)

Background  Hyperinsulinaemia has been suggested as an important factor for developing hypokalaemic paralysis in patients with thyrotoxic periodic paralysis (TPP). Since hyperinsulinaemia is a common feature of insulin resistance, there may be a causal relationship between insulin resistance and TPP.
Objective  To compare insulin sensitivity between subjects with a history of TPP and others with a history of thyrotoxicosis without periodic paralysis.
Methods  Insulin sensitivity measured by euglycaemic hyperinsulinaemic clamp and 75-g oral glucose tolerance test (OGTT) were performed nonselectively in 10 subjects with a history of TPP (TPP group) and 10 age- and sex-matched subjects with a history of simple thyrotoxicosis (control group). All participants had euthyroidism and fasting plasma glucose of < 5·55 mmol/l at the time of the study.
Results  Body mass index and waist circumference of the TPP group were higher than that of the control group. One of 10 (10%) subjects in the TPP group and 6 of 10 (60%) in the control group had BMI of < 23 kg/m². Areas under the curve (AUC) of plasma glucose after OGTT were comparable, while the AUC of serum insulin of the TPP group was higher than in the control group. The TPP group had lower insulin sensitivity than the control group.
Conclusion  The subjects with a history of TPP were more obese and had lower insulin sensitivity than those with a history of simple thyrotoxicosis. Insulin resistance with compensatory hyperinsulinaemia may be a key feature of the pathogenesis of TPP.     

Gastric volvulus caused by percutaneous endoscopic gastrostomy: a case report

Percutaneous endoscopic gastrostomy is commonly performed for enteric feeding in children with neurologic impairment because of its low rates of complication. We report a case of gastric volvulus, an unusual complication, after percutaneous endoscopic gastrostomy procedure in our institution.     

Subclinical subretinal fluid detectable only by optical coherence tomography in choroidal naevi—the SON study

BackgroundSubretinal fluid is a risk factor for growth and malignant transformation of choroidal naevi, however it is unclear if this applies to subclinical fluid that is only detectable by optical coherence tomography (OCT). The objective of this study was to determine the prevalence and associations of subclinical but OCT-detectable subretinal fluid over choroidal naevi.MethodsCross-sectional study of 309 consecutive cases of choroidal naevi imaged by OCT between July 2017 to January 2019. Multicentre international study involving ten retinal specialist centres. All patients presenting to retinal specialists had routine clinical examination and OCT imaging. The prevalence of subclinical OCT-detectable subretinal fluid over choroidal naevi and its associations with other features known to predict growth and malignant transformation were noted and analysed.ResultsOf 309 identified consecutive cases, the mean patient age was 65 years, 89.3% of patients were Caucasian and 3.9% were Asian. The prevalence of subclinical but OCT-detectable subretinal fluid associated with choroidal naevi was 11.7% (36/309). Naevi with fluid were associated with larger basal diameters, greater thickness, presence of a halo, orange pigmentation, hyperautofluorescence, and hypodensity on B-scan ultrasonography.Conclusion and relevanceOf choroidal naevi where subretinal fluid is not visible on clinical examination, 11.7% demonstrate subretinal fluid on OCT scans. These naevi more commonly exhibit features known to be associated with growth and transformation to melanoma. The presence of subclinical OCT-detectable fluid over choroidal naevi may assist in their risk stratification.Subject terms: Risk factors, Uveal diseases, Eye manifestations     

Titania Nanotube Architectures Synthesized on 3D-Printed Ti-6Al-4V Implant and Assessing Vancomycin Release Protocols

The aim of this study is to synthesize Titania nanotubes (TNTs) on the 3D-printed Ti-6Al-4V surface and investigate the loading of antibacterial vancomycin drug dose of 200 ppm for local drug treatment application for 24 h. The antibacterial drug release from synthesized nanotubes evaluated via the chemical surface measurement and the linear fitting of Korsmeyer–Peppas model was also assessed. The TNTs were synthesized on the Ti-6Al-4V surface through the anodization process at different anodization time. The TNTs morphology was characterized using field emission scanning electron microscope (FESEM). The wettability and the chemical composition of the Ti-6Al-4V surface and the TNTs were assessed using the contact angle meter, Fourier transform infrared spectrophotometer (FTIR) and the X-ray photoelectron spectroscopy (XPS). The vancomycin of 200 ppm release behavior under controlled atmosphere was measured by the high-performance liquid chromatography (HPLC) and hence, the position for retention time at 2.5 min was ascertained. The FESEM analysis confirmed the formation of nanostructured TNTs with vertically oriented, closely packed, smooth and unperforated walls. The maximum cumulative vancomycin release of 34.7% (69.5 ppm) was recorded at 24 h. The wetting angle of both Ti-6Al-4V implant and the TNTs were found below 90 degrees. This confirmed their excellent wettability.     

Capacity building in screening and treatment of diabetic retinopathy in Asia-Pacific region

The focus of capacity building for screening and treatment of diabetic retinopathy (DR) is on health professionals who are nonophthalmologists. Both physicians and nonphysicians are recruited for screening DR. Although there is no standardization of the course syllabus for the capacity building, it is generally accepted to keep their sensitivity >80%, specificity >95%, and clinical failure rate <5% for the nonophthalmologists, if possible. A systematic literature search was performed using the PubMed database and the following search terms: diabetic retinopathy, diabetic retinopathy screening, Asia, diabetic retinopathy treatment, age-related macular degeneration, capacity building, deep learning, artificial intelligence (AI), nurse-led clinic, and intravitreal injection (IVI). AI may be a tool for improving their capacity. Capacity building on IVIs of antivascular endothelial growth factors for DR is focused on nurses. There is evidence that, after a supervision of an average of 100 initial injections, the trained nurses can do the injections effectively and safely, the rate of endophthalmitis ranges from 0.03 to 0.07%, comparable to ophthalmologists. However, laws and regulations, which are different among countries, are challenges and barriers for nonophthalmologists, particularly for nonphysicians, for both screening and treatment of DR. Even if nonphysicians or physicians who are nonophthalmologists are legally approved for these tasks, sustainability of the capacity is another important challenge, this may be achieved if the capacity building can be part of their career development. Patient acceptability is another important barrier for initiating care provided by nonophthalmologists, particularly in Asia. There are also collaborations between national eye institutes of high-income countries, nongovernment organizations, and local eye institutes to improve both the quality and quantity of ophthalmologists and retinal specialists in low-income countries in Asia. This approach may require more labor, cost, and time consuming than training nonophthalmologists.     

Cost-minimization analysis of sequential genetic testing versus targeted next-generation sequencing gene panels in patients with pheochromocytoma and paraganglioma

IntroductionPheochromocytomas and paragangliomas (PPGLs) are highly heritable tumours, with up to 40% of cases carrying germline variants. Current guidelines recommend genetic testing for all patients with PPGLs. Next-generation sequencing (NGS) enables accurate, fast, and inexpensive genetic testing. This study aimed to compare the costs related to PPGL genetic testing between the sequential testing using the decisional algorithm proposed in the 2014 Endocrine Society guidelines and targeted NGS gene panels.MethodsPatients with proven PPGLs were enrolled. A gene list covering 17 susceptibility genes related to hereditary PPGLs was developed for targeted sequencing. Validation was carried out by Sanger sequencing. We simulated the diagnostic workflow to examine the anticipated costs based on each strategy for genetic testing.ResultsTwenty-nine patients were included, among whom a germline variant was identified in 34.5%. A total of 22.7% with apparently sporadic PPGL carried a variant. Five genes were involved (RET, n = 3; SDHB, n = 3; SDHD, n = 2; EGLN1, n = 1; and NF1, n = 1). According to the diagnostic workflow, the average cost of the targeted NGS (534.7 US dollars per patient) is lower than that of the sequential testing (734.5 US dollars per patient). The targeted NGS can also reduce the number of hospital visits from 4.1 to 1 per person. The cost can be further reduced to 496.24 US dollars per person (32% reduction) if we apply a new syndromic-driven diagnostic algorithm to establish priorities for specific genetic testing for syndromic and selected cases, and targeted NGS for non-syndromic patients.ConclusionsTargeted NGS can reduce both the cost of PPGL genetic testing and the number of hospital visits, compared with the conventional approach. Our proposed algorithm is the preferred approach due to its significant reduction of the cost of genetic testing.

Key message

• Pheochromocytomas and paragangliomas are highly heritable neoplasms.
• The targeted next-generation sequencing (NGS) gene panels have proven to be fast, accurate, and inexpensive for the genetic analysis.
• According to this cost analysis, it is economically reasonable to use targeted NGS gene panels for genetic screening.

     

Salivary gland proteome of the human malaria vector, Anopheles campestris-like (Diptera: Culicidae)

Anopheles campestris-like is proven to be a high-potential vector of Plasmodium vivax in Thailand. In this study, A. campestris-like salivary gland proteins were determined and analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), two-dimensional gel electrophoresis, and nano-liquid chromatography-mass spectrometry. The total amount of salivary gland proteins in the mosquitoes aged 3–5 days was approximately 0.1?±?0.05 μg/male and 1.38?±?0.01 μg/female. SDS-PAGE analysis revealed at least 12 major proteins found in the female salivary glands and each morphological region of the female glands contained different major proteins. Two-dimensional gel electrophoresis showed approximately 20 major and several minor protein spots displaying relative molecular masses from 10 to 72 kDa with electric points ranging from 3.9 to 10. At least 15 glycoproteins were detected in the female glands. Similar electrophoretic protein profiles were detected comparing the male and proximal-lateral lobes of the female glands, suggesting that these lobes are responsible for sugar feeding. Blood-feeding proteins, i.e., putative 5′-nucleotidase/apyrase, anti-platelet protein, long-form D7 salivary protein, D7-related 1 protein, and gSG6, were detected in the distal-lateral lobes (DL) and/or medial lobes (ML) of the female glands. The major spots related to housekeeping proteins from other arthropod species including Culex quinquefasciatus serine/threonine-protein kinase rio3 expressed in both male and female glands, Ixodes scapularis putative sil1 expressed in DL and ML, and I. scapularis putative cyclophilin A expressed in DL. These results provide information for further study on the salivary gland proteins of A. campestris-like that are involved in hematophagy and disease transmission.     

Novel insulin sensitivity index derived from oral glucose tolerance test

The euglycemic hyperglycemic clamp is generally regarded as a reference method for assessing insulin sensitivity. However, this method is laborious and expensive. The oral glucose tolerance test (OGTT), the most commonly used method for evaluating whole body glucose tolerance, has often been used to assess insulin sensitivity. In the previous studies the correlation between the insulin sensitivity index (ISI) obtained from the OGTT (ISI(OGTT)) and those obtained from the glucose clamp (ISI(Clamp)) may not be satisfactory. This is because the glucose clamp study is designed for measuring peripheral glucose utilization, whereas plasma glucose responses during the OGTT are the results of peripheral glucose utilization and hepatic glucose production. Based on this problem, we developed a new equation, ISI(OGTT), [1.9/6 x body weight (kg) x fasting plasma glucose (mmol/liter) + 520 - 1.9/18 x body weight x area under the glucose curve (mmol/h.liter) - urinary glucose (mmol)/1.8] / [area under the insulin curve (pmol/h.liter) x body weight], which would represent peripheral glucose utilization only. We tested our equation with ISI(Clamp) and also compared with others. Thirty-three healthy volunteers (16 males) with normal glucose tolerance underwent a 75-g, 3-h OGTT on the morning of d 1 and a glucose clamp on the morning of d 2. Their mean (+/-SD) age and body mass index were 30.8 +/- 8.3 yr and 22.0 +/- 3.9 kg/m(2), respectively. The mean (+/-SD) glucose disposal rate and ISI determined by glucose clamp were 27.46 +/- 16.55 micro mol/kg.min and 7.39 +/- 2.72 micro mol/kg.min/pmol.liter, respectively. Pearson's correlation coefficient between our ISI(OGTT) and ISI(Clamp) was 0.869 (P < 0.0001) which was stronger than those corresponding values calculated from HOMA, QUICKI, Belfiore, Cederholm, Gutt, Matsuda, and Stumvoll, the respective values of which were 0.404, 0.434, 0.643, 0.533, 0.584, 0.734, and 0.508. In conclusion, the ISI(OGTT) derived from our equation is more suitable than others in assessing insulin sensitivity in subjects with normal glucose tolerance. Further studies in subjects with impaired glucose tolerance and diabetes mellitus should be performed to confirm the validity of this equation.