SUCCESSFUL PREGNANCY OUTCOME IN PATIENT WITH NIEMANN-PICK DISEASE TYPE B AND REVIEW OF THE LITERATURE.

Niemann-Pick disease (NPD), is a rare autosomal recessive lysosomal storage disorder. Niemann-Pick A and B are caused by homozygous or compound heterozygous mutations in the sphingomyelin phosphodiesterase-1 (SMPD1) gene on chromosome 11p15. Type B is panethnic, although its frequency is increased in Turkish, Arabic and North African populations. Clinical features vary significantly among patients. It is a rare condition and information about its management an outcome during pregnancy and labor is limited. Both maternal mortality and morbidity due to severe postpartum hemorrhage has been reported. We represent a case of successful pregnancy outcome in patient with NPD type B. Type of mutations in SMPD 1 gene and severity of disease before pregnancy can predict the prognosis of pregnancy.

New insights into the history of domesticated and wild apricots and its contribution to Plum pox virus resistance.

Studying domesticated species and their wild relatives allows understanding of the mechanisms of population divergence and adaptation, and identifying valuable genetic resources. Apricot is an important fruit in the Northern hemisphere, where it is threatened by the Plum pox virus (PPV), causing the sharka disease. The histories of apricot domestication and of its resistance to sharka are however still poorly understood. We used 18 microsatellite markers to genotype a collection of 230 wild trees from Central Asia and 142 cultivated apricots as representatives of the worldwide cultivated apricot germplasm; we also performed experimental PPV inoculation tests. The genetic markers revealed highest levels of diversity in Central Asian and Chinese wild and cultivated apricots, confirming an origin in this region. In cultivated apricots, Chinese accessions were differentiated from more Western accessions, while cultivated apricots were differentiated from wild apricots. An approximate Bayesian approach indicated that apricots likely underwent two independent domestication events, with bottlenecks, from the same wild population. Central Asian native apricots exhibited genetic subdivision and high frequency of resistance to sharka. Altogether, our results contribute to the understanding of the domestication history of cultivated apricot and point to valuable genetic diversity in the extant genetic resources of wild apricots.

Novel ITGB6 mutation in autosomal recessive amelogenesis imperfecta.

OBJECTIVE: Hereditary defects in tooth enamel formation, amelogenesis imperfecta (AI), can be non-syndromic or syndromic phenotype. Integrins are signaling proteins that mediate cell-cell and cell-extracellular matrix communication, and their involvement in tooth development is well known. The purposes of this study were to identify genetic cause of an AI family and molecular pathogenesis underlying defective enamel formation. MATERIALS AND METHODS: We recruited a Turkish family with isolated AI and performed mutational analyses to clarify the underlying molecular genetic etiology. RESULTS: Autozygosity mapping and exome sequencing identified a novel homozygous ITGB6 transversion mutation in exon 4 (c.517G>C, p.Gly173Arg). The glycine at this position in the middle of the ßI-domain is conserved among a wide range of vertebrate orthologs and human paralogs. Clinically, the enamel was generally thin and pitted with pigmentation. Thicker enamel was noted at the cervical area of the molars. CONCLUSIONS: In this study, we identified a novel homozygous ITGB6 mutation causing isolated AI, and this advances the understanding of normal and pathologic enamel development.

Differential Corticospinal Excitability and Cortical Functional Connectivity Modulation by Spinal Cord Transcutaneous Stimulation-based Motor Training versus Motor Training alone in Able-bodied and SCI participants: A Multiple Case Study.

Spinal cord transcutaneous stimulation (scTS) has shown its potential for boosting motor, sensory, and autonomic function recovery after a spinal cord injury. Despite the demonstrated benefits, little is known about the exact neuromodulatory mechanisms triggered by scTS and the cortex involvement in the beneficial effects observed. Here, we examine the effects of scTS-based motor training and motor training alone on sensorimotor cortical functional connectivity and corticospinal excitability in able-bodied and SCI participants.Clinical Relevance- The results show preliminary evidence of differential cortical involvement and modulation by scTS-based motor training in uninjured and spinal-cord injured individuals. A better understanding of scTS mechanisms of action could help optimize the intervention design and potentiate its benefits.

Allele mining of eukaryotic translation initiation factor genes in Prunus for the identification of new sources of resistance to sharka.

Members of the eukaryotic translation initiation complex are co-opted in viral infection, leading to susceptibility in many crop species, including stone fruit trees (Prunus spp.). Therefore, modification of one of those eukaryotic translation initiation factors or changes in their gene expression may result in resistance. We searched the crop and wild Prunus germplasm from the Armeniaca and Amygdalus taxonomic sections for allelic variants in the eIF4E and eIFiso4E genes, to identify alleles potentially linked to resistance to Plum pox virus (PPV). Over one thousand stone fruit accessions (1397) were screened for variation in eIF4E and eIFiso4E transcript sequences which are in single copy within the diploid Prunus genome. We identified new alleles for both genes differing from haplotypes associated with PPV susceptible accessions. Overall, analyses showed that eIFiso4E is genetically more constrained since it displayed less polymorphism than eIF4E. We also demonstrated more variations at both loci in the related wild species than in crop species. As the eIFiso4E translation initiation factor was identified as indispensable for PPV infection, a selection of ten different eIFiso4E haplotypes along 13 accessions were tested by infection with PPV and eight of them displayed a range of reduced susceptibility to resistance, indicating new potential sources of resistance to sharka.

Loss of genetic diversity as a signature of apricot domestication and diffusion into the Mediterranean Basin.

BACKGROUND: Domestication generally implies a loss of diversity in crop species relative to their wild ancestors because of genetic drift through bottleneck effects. Compared to native Mediterranean fruit species like olive and grape, the loss of genetic diversity is expected to be more substantial for fruit species introduced into Mediterranean areas such as apricot (Prunus armeniaca L.), which was probably primarily domesticated in China. By comparing genetic diversity among regional apricot gene pools in several Mediterranean areas, we investigated the loss of genetic diversity associated with apricot selection and diffusion into the Mediterranean Basin. RESULTS: According to the geographic origin of apricots and using Bayesian clustering of genotypes, Mediterranean apricot (207 genotypes) was structured into three main gene pools: 'Irano-Caucasian', 'North Mediterranean Basin' and 'South Mediterranean Basin'. Among the 25 microsatellite markers used, only one displayed deviations from the frequencies expected under neutrality. Similar genetic diversity parameters were obtained within each of the three main clusters using both all SSR loci and only 24 SSR loci based on the assumption of neutrality. A significant loss of genetic diversity, as assessed by the allelic richness and private allelic richness, was revealed from the 'Irano-Caucasian' gene pool, considered as a secondary centre of diversification, to the northern and southwestern Mediterranean Basin. A substantial proportion of shared alleles was specifically detected when comparing gene pools from the 'North Mediterranean Basin' and 'South Mediterranean Basin' to the secondary centre of diversification. CONCLUSIONS: A marked domestication bottleneck was detected with microsatellite markers in the Mediterranean apricot material, depicting a global image of two diffusion routes from the 'Irano-Caucasian' gene pool: North Mediterranean and Southwest Mediterranean. This study generated genetic insight that will be useful for management of Mediterranean apricot germplasm as well as genetic selection programs related to adaptive traits.

Root canal treatment of a periradicular lesion caused by unintentional root damage after orthodontic miniscrew placement: a case report.

AIM: To present the successful endodontic management of a maxillary lateral incisor tooth with a periradicular lesion caused by unintentional root damage after orthodontic miniscrew placement. SUMMARY: A 22-year-old female was diagnosed with a skeletal Class II, Division 2 malocclusion with Class II molar and canine relationships on both sides. The treatment plan included distalization of the maxillary first molars bilaterally followed by full fixed appliance therapy. For the maxillary molar distalization, an appliance in conjunction with a miniscrew anchorage system was designed. Two months later, the patient came to the clinic with complaints of pain in the maxillary right lateral incisor region. On intraoral examination, intraoral sinus tracts were detected in the maxillary right buccal sulcus and palate. A large radiolucent lesion with a well-defined margin around the root of the maxillary right lateral incisor was seen. Root canal treatment was performed on the maxillary right lateral incisor tooth. The root canal was filled with gutta-percha and AH Plus sealer, using a lateral compaction technique. The final restoration of the tooth was completed using composite, and the tooth was reviewed after 10 months. The tooth was asymptomatic and radiographically showed repair of the lesion. Healing was achieved without any need for further endodontic or surgical intervention. Key learning points • This case illustrates the need to take care with miniscrews when performing orthodontic treatment, especially when the miniscrews are in close proximity to root apices. • The periradicular lesion as a result of miniscrew damage was successfully treated with root canal treatment.

Analysis of the involvement of the thyroid gland using computed tomography in patients with suspected SARS-CoV-2 infection: a retrospective study.

OBJECTIVE: SARS-CoV-2 primarily infects the respiratory tract and leads to severe pneumonia by binding to the ACE-2 receptor. The virus can also interact with ACE-2 receptors expressed in other tissues as in thyroid. This study predicted the complications involving the thyroid in patients with suspected SARS-CoV-2. PATIENTS AND METHODS: Patients with suspected SARS-CoV-2 infection between March 11, 2020-May 31, 2020 were retrospectively evaluated. Sixty-nine patients who were radiologically diagnosed as COVID-19 according to thoracic CT and had previously performed thoracic CT before November 2019 were included in the study according to the exclusion and inclusion criteria. Age and gender-matched controls (No. 69) were selected with normal thoracic CT whose PCR tests were also negative. Thyroid densities of participants were calculated and compared from the previous and current thoracic CTs. Results were also compared with the control group. RESULTS: Participants were composed of 69 patients (39 male, mean age 64.35 years). Thyroid densities were significantly decreased from 89HU to 76HU for whole gland, from 88HU to 76HU for right lobes and from 87.5HU to 75.5HU for left lobes at current thoracic CTs performed during COVID-19 (p<0.001, p<0.001, p<0.001 respectively). The decrease in densities of the whole thyroid gland, both left and right lobes, was correlated with mortality (p<0.001). The changes in thyroid densities were not correlated with age nor gender. The decreases in HU values of thyroid densities for whole gland, left and right lobes, were correlated with mortality (p<0.001, p<0.001, and p<0.001 respectively). CONCLUSIONS: COVID-19 is a multi-systemic disease that threatens vital organs, including the thyroid. Future studies are needed to investigate the association between SARS-CoV-2 and other complications.

Alteration of Exon Definition Causes Amelogenesis Imperfecta.

Amelogenesis imperfecta (AI) is a collection of genetic disorders affecting the quality and/or quantity of tooth enamel. More than 20 genes are, so far, known to be responsible for this condition. In this study, we recruited 3 Turkish families with hypomaturation AI. Whole-exome sequence analyses identified disease-causing mutations in each proband, and these mutations cosegregated with the AI phenotype in all recruited members of each family. The AI-causing mutations in family 1 were a novel AMELX mutation [NM_182680.1:c.143T>C, p.(Leu48Ser)] in the proband and a novel homozygous MMP20 mutation [NM_004771.3:c.616G>A, p.(Asp206Asn)] in the mother of the proband. Previously reported compound heterozygous MMP20 mutations [NM_004771.3:c.103A>C, p.(Arg35=) and c.389C>T, p.(Thr130Ile)] caused the AI in family 2 and family 3. Minigene splicing analyses revealed that the AMELX missense mutation increased exonic definition of exon 4 and the MMP20 synonymous mutation decreased exonic definition of exon 1. These mutations would trigger an alteration of exon usage during RNA splicing, causing the enamel malformations. These results broaden our understanding of molecular genetic pathology of tooth enamel formation.

The effects of raloxifene and tibolone on homocysteine and vascular histopathological changes.

The aim of the present study was to examine the effects of raloxifene (RLX) and tibolone (TBN) on plasma homocysteine (Hcy) levels and their relationship with atherosclerotic changes in the walls of the carotid artery in ovariectomised rats. Thirty surgically ovariectomised Wistar albino rats after a menopausal period of 6 cycles were randomly assigned to receive RLX 0.01 mg/kg/day (n=10), TBN 0.04 mg/kg/day (n=10) and the same dose of placebo (n=10) for 6 cycles. Serum levels of vitamin B12, folate and Hcy were measured and carotid arteries were examined histopathologically following the termination of treatment. Hcy levels were 3.27+/-0.97, 2.57+/-0.32 and 2.28+/-0.12 micromol/l, Vitamin B12 levels were 901.90+/-239.76, 694.70+/-112.20 and 631+/-309.44 pg/ml and folate levels were 73.80+/-12.71, 72.51+/-7.05 and 84.79+/-20.82 ng/ml in receiving RLX, TBN and placebo respectively. Hcy levels were increased by RLX vs. placebo (P=0.006) but not by TBN vs. placebo (P=0.070). Vitamin B12 levels were found to be elevated by TBN vs. the control group (P=0.041) but not by RLX vs. placebo (P=0.059). Histopathological examination of carotid arteries from rats receiving both RLX and TBN revealed no difference vs. placebo. Data obtained from the study support the view that neither RLX nor TBN appears to have a primary protective effect on vascular disease by effecting the metabolism of Hcy at menopause.

Mandibular symphyseal distraction osteogenesis: review of three techniques.

Mandibular symphyseal distraction osteogenesis (MSDO) is an alternative strategy to correct mandibular transverse deficiencies and dental crowding. Only a limited number of practitioners have reported their clinical experience and potential complications of this procedure to widen the mandible in a large case series. This study involved retrospective analysis of 40 patients who underwent mandibular symphyseal distraction osteogenesis. Three different types of distractor were used to widen the mandible: tooth-borne in 21 patients, bone-borne in 5 patients and hybrid (both bone and tooth-borne) in 14 patients. The distraction amount ranged from 7 to 11 mm (mean 7.31 mm). While 39 patients underwent successful mandibular symphyseal distraction, there was one failure. Most of the complications were experienced in bone-borne distractors, such as breakage of the distractor rod, gingival recession, secondary infection and ptosis of the chin. In the light of these findings, it is suggested that a lingually placed tooth-borne hyrax appliance is more suitable and reliable than the other distraction devices. Further larger studies are needed in order to better evaluate the effectiveness of bone-borne or hybrid devices.

The effects of hormone replacement therapy on homocysteine and vascular histopathological changes.

The aim of the present study was to examine the effects of hormone replacement therapy on homocysteine and its relationship with atherosclerotic changes. Twenty Wistar albino rats were deployed in the study. An artificial menopause was created. Rats were randomly assigned to 2 groups. The first group received 6 cycles of 0.01 mg/kg/day conjugated equine oestrogen and the second group received the same dose of placebo. After the treatment, vitamin B12, folate and homocysteine levels were measured. Carotid arteries were removed for histopathological examination of vascular effects. Homocysteine levels were 3.35+/-0.22 and 2.28+/-0.12 micromol/l, vitamin B12 levels were 699+/-87.51 and 631+/-97.85 pg/ml and folate levels were 71.83+/-4.03 and 84.79+/-6.58 ng/ml in Groups 1 and 2, respectively. Statistical analyses revealed no significant differences between Group 1 and Group 2 with regard to vitamin B12 and folate levels. Homocysteine was found to be significantly elevated in Group 1 (P = 0.001). Histopathological examination did not reveal any pathological finding in vascular sections in either group. Even though postmenopausal HRT is not used as a means of cardiovascular protection, it is the only treatment available for vasomotor symptoms and prevention of urogenital atrophy during menopause. Until the relationships between menopause, HRT, homocysteine, folate and vitamin B12 are clearly elucidated with more comprehensive studies, including all the details leading to plasma homocysteine increment in homocysteine metabolism, we recommend that menopausal women should be provided with accurate information and risk/benefit analysis on HRT treatment and the decision should be made by the patient.

Clinical and oral findings of a patient with Simpson-Golabi-Behmel syndrome.

BACKGROUND: The Simpson-Golabi-Behmel syndrome (SGBS) is an overgrowth condition characterised by macrosomia, mental deficiency, large head, prominent skull sutures, midface deficiency, hypertelorism, broad nose, wide mouth, macroglossia, malocclusion, highly arched palate, and musculoskeletal and limb abnormalities. The aim of this case report is to present clinical and oral findings of an 8-year-old boy who had been diagnosed with SGBS. CASE REPORT: This patient had supernumerary nipples on the right side, cubitus valgus webbed fingers, scoliosis, umbilical hernia, a coarse face, macrocephaly, hypertelorism, a short broad nose, a wide mouth, a straight facial profile and hearing loss. The patient also had macroglossia, diastemas, over-retained primary tooth, absent mandibular permanent central incisors, and highly arched palate. Lateral cephalometric analysis revealed a large anterior cranial base, a large maxilla and mandible, a large inferior face height, and skeletal Class III jaw relationship. FOLLOW-UP: After extraction of the over-retained primary central tooth, a partial prosthesis was fabricated in order to maintain function. The patient has been recalled regularly at 6-month intervals for 2 years. Over the following years the prosthesis was replaced due to facial growth. CONCLUSION: Long term follow-up is essential for the patient with SGBS. Preventive dental care, including oral hygiene instructions, diet counselling and the use of fluoride has been implemented.

Novel MMP20 and KLK4 Mutations in Amelogenesis Imperfecta.

In order to achieve highly mineralized tooth enamel, enamel proteinases serve the important function of removing the remaining organic matrix in the mineralization and maturation of the enamel matrix. Mutations in the kallikrein 4 (KLK4), enamelysin (MMP20), and WDR72 genes have been identified as causing hypomaturation enamel defects in an autosomal-recessive hereditary pattern. In this report, 2 consanguineous families with a hypomaturation-type enamel defect were recruited, and mutational analysis was performed to determine the molecular genetic etiology of the disease. Whole exome sequencing and autozygosity mapping identified novel homozygous mutations in the KLK4 (c.620_621delCT, p.Ser207Trpfs*38) and MMP20 (c.1054G>A, p.Glu352Lys) genes. Further analysis on the effect of the mutations on the translation, secretion, and function of KLK4 and MMP20 revealed that mutant KLK4 was degraded intracellularly and became inactive while mutant MMP20 was expressed at a normal level but secreted only minimally with proteolytic function.

Hydatic cyst located intermuscular area of the forearm: MR imaging findings.

Hydatid cyst of the skeletal muscle is rare and can pose various diagnostic problems. The authors report the case of a patient with primary hydatid cysts localized to intermuscular area of the forearm, emphasizing the diagnostic value of MRI. To the best of our knowledge, this localization of the hydatic cyst has not been reported to date.

The Chiari III malformation: an unusual and asymptomatic variant in an 11-year old child.

Chiari III malformation is an extremely rare condition, and is characterized by the hindbrain herniation into a low occipital or high cervical encephalocele together with the pathologic and imaging features of the Chiari II malformation. In this report, an unusual variant of the Chiari III malformation was diagnosed in an 11-year-old girl. She had an encephalocele operation when she was a newborn, and has been asymptomatic since then. The clinical and imaging findings of this case were presented.

Twin reversed arterial perfusion sequence in conjoined, acardiac, acephalic twins associated with a normal triplet. A case report.

BACKGROUND: Twin reversed arterial perfusion (TRAP) sequence and development of an acardiac monster is a rare event. Even more rare are conjoined acardiac, acephalic twins complicating a triplet pregnancy with TRAP sequence. The mortality for the acardius is 100%, and morbidity for the normal, pump fetus is 50%. The morbidity of the pump twin or triplet is attributed mostly to in utero congestive heart failure. CASE: A 24-year-old woman, gravida 1, para 0, at 35 weeks' intrauterine pregnancy, gave birth via low transverse cesarean section to a normal female and a pair of conjoined, acardiac, acephalic, pelvipagus twins. CONCLUSION: The diagnosis of acardius in multiple gestation pregnancy, with no fetal heart tone on ultrasound, must be ruled out in every case so that proper counseling, management and avoidance of complications in these patients can be achieved.

Conservative management of intrahepatic perforation of the gallbladder secondary to acalculous cholecystitis.

Gallbladder (GB) perforation is a rare complication of acute acalculous cholecystitis. This complication mostly manifests as acute free perforation into the peritoneal cavity, subacute pericholecystic abscess, or chronic perforation with cholecystoenteric fistula. Perforation of the GB into the liver is extremely rare, and was reported only in adults, of whom all were treated surgically. The authors present an intrahepatic GB perforation secondary to acute acalculous cholecystitis, and its successful conservative management in a 13-year-old boy.

Automatic analysis of the control of metabolic networks.

In this paper we apply computer algebra techniques to analyze the control of metabolic networks. For this purpose, a computer program based on metabolic control theory was developed. When a stoichiometry matrix of the metabolic networks is given, the program calculates all the control coefficients (flux and metabolic control coefficients, summation and connectivity relationships) using elasticity coefficients. The program can be applied to any metabolic network which includes unlimited steps and intermediate metabolites.

Unusual malformations in occult spinal dysraphism.

Two cases of occult spinal dysraphism with different clinical symptoms, signs and congenital pathologies are presented. One had malformations including scoliosis, dermoid tumor, hydromyelia, diastematomyelia, dermal sinus, low conus, vertebrae anomalies and dextrocardia. The occurrence of dextrocardia in association with occult spinal dysraphism was found to be extremely unusual. The second case is presented in relation to the rarity of teratoma with dermal sinus and tethered cord in the lumbar area. Myelography, computed tomography, (CT), Myelo CT and magnetic resonance were used in making a diagnosis.