A novel mutation in lysophosphatidic acid receptor 6 gene in autosomal recessive hypotrichosis and evidence for a founder effect

Mutations in the lysophosphatidic acid receptor 6 (LPAR6) gene cause localized autosomal recessive hypotrichosis. We report six consanguineous families from Pakistan with segregating hypotrichosis localized to the scalp. Genetic investigation using polymorphic microsatellite markers revealed homozygosity spanning the LAH3 locus on chromosome?13 in affected individuals of all six families. Sequence analysis of the LPAR6 gene showed a novel insertion resulting in a frameshift and a premature termination (p.I194FfsX11) in affected members of one family. In the remaining five families we identified a previously described missense mutation (p.G146R) in a homozygous state in affected members. The closest flanking polymorphic marker showed an identical allele size in the five families segregating with the p.G146R mutation, supporting a single origin of this variation. These findings extend the spectrum of known LPAR6 mutations and suggest a founder effect of the p.G146R mutation in the Pakistani population.     

Patterns of ambulatory activity in subjects with and without intermittent claudication

PURPOSE: This study compared the patterns of ambulatory activity in subjects with and without intermittent claudication. METHODS: The study participants were 98 subjects limited by intermittent claudication and 129 controls who were matched for age, gender, and race. Subjects were assessed on their ambulatory activity patterns for 1 week with a small, lightweight step activity monitor attached to the ankle using elastic Velcro (Velcro Industries BV, Manchester, NH) straps above the lateral malleolus of the right leg. The step activity monitor recorded the number of strides taken on a minute-to-minute basis, the time spent ambulating, and the time and number of strides measured at low (<15 strides/min), medium (15 to 30 strides/min), and high (>30 strides/min) cadences. RESULTS: Subjects with intermittent claudication took fewer total strides each day than the controls (3149 +/- 1557 strides/d vs 4230 +/- 1708 strides/d; P < .001) and fewer strides at medium (1228 +/- 660 strides/day vs 1638 +/- 724 strides/day; P = .001) and high (766 +/- 753 strides/day vs 1285 +/- 1029 strides/day; P < .001) cadences. Subjects with intermittent claudication also had a lower daily average cadence than the controls (11.8 +/- 2.9 strides/min vs 13.5 +/- 3.1 strides/min; P < .001) and spent less total time ambulating each day (264 +/- 109 min/day vs 312 +/- 96 min/day; P = .034), primarily at medium (58 +/- 30 min/day vs 75 +/- 32 min/day; P < .001) and at high (19 +/- 17 min/day vs 30 +/- 22 min/day; P = .001) cadences. CONCLUSION: Intermittent claudication is associated with lower total daily ambulatory activity owing both to less time ambulating and to fewer strides taken while ambulating, particularly at moderate and high cadences.     

Multidisciplinary management of ductal carcinoma in situ: a 10-year experience

BACKGROUND: Two ductal carcinoma in situ (DCIS) treatment controversies are (1) what is the preferred margin for patients undergoing lumpectomy plus radiation, and (2) is there a subgroup that can be safely treated with lumpectomy alone? A multidisciplinary team was established to evaluate these issues. METHODS: Patients with DCIS who were candidates for breast-conservation were divided into 2 groups. Group 1 had a minimum 5-mm margin and received radiation, and group 2 had a minimum 10-mm margin and received no radiation. RESULTS: One hundred fifty-two patients (153 cancers) met the inclusion criteria. The median follow-up was 8.2 years. Overall, there were 6 recurrences (3.92%); 1 of 71 recurred in group 1 (1.40%), and 5 of 82 recurred in group 2 (6.01%). CONCLUSION: Five-millimeter margins plus radiation results in low rates of recurrence. A subgroup of DCIS patients can be identified in which radiation can be safely avoided. The multidisciplinary team approach to managing DCIS enhances the potential for improved outcomes.     

Increased GABA<Subscript>B</Subscript> Receptor Subtype Expression in the Nucleus of the Solitary Tract of the Spontaneously Hypertensive Rat

Expression of GABA(B) receptor messenger RNA (mRNA) in the central nervous system was compared between the spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rat. Polymerase chain reaction (PCR) revealed all the isoforms except B1e in cortex, hypothalamus, and medulla oblongata. In the nucleus of the solitary tract (NTS) and ventrolateral medulla (VLM), the B1a-c and 1 g isoforms were present as well as B2. Real-time PCR detected significantly higher levels of B1a (p < 0.01) and B2 (p < 0.05) mRNA in the NTS of SHR compared to WKY. A significant increase in B1a expression (p < 0.05) was detected in VLM. Immunolabeling suggested presynaptic and postsynaptic expression of B1a, B1b, and B2 subtypes throughout the NTS, with significant differences in distribution patterns and labeling between subtypes and between SHR and WKY. These findings suggest that GABA(B) receptors expressed by neurones in NTS may be involved in cardiovascular regulation and that changes in GABA(B) mRNA expression levels may contribute to the hypertensive state in SHR.     

Investigating socio-economic-demographic determinants of tobacco use in Rawalpindi,Pakistan

Background  

To investigate the socio-economic and demographic determinants of tobacco use in Rawalpindi, Pakistan.     

Selective or Routine Histology of Cholecystectomy Specimens for Diagnosing Incidental Carcinoma of Gallbladder and Correlation with Careful Intraoperative Macroscopic Examination? A Systematic Review

Background: Selective or Routine histology of cholecystectomy specimens for benign gallbladder disease has always been a matter of debate because of the low prevalence and bad prognosis associated with gall bladder carcinoma. The objective of this study is to ascertain whether selective histology can be preferred over Routine histology without any harm. Methods: This systematic review is conducted according to PRISMA’s checklist; relevant articles were searched in the database until September 1 2020 in PubMed, Scopus, Science Direct, and Web of Science databases, manually, with search queries and without date restrictions. Studies included in this systematic review involved patients who underwent cholecystectomy for benign gallbladder disease and were diagnosed with gallbladder carcinoma incidentally either after selective or routine histology of the gallbladder. Results: A total of 24 routine or selective histology recommending studies were selected for the systematic review after following the inclusion and exclusion criteria. These studies comprised 77,213 numbers of patients and 486 numbers of Malignancies. These studies correlate the number of IGBC diagnosed histologically with the number of IGBC’s that were suspected by the surgeons intraoperative by macroscopy. Routine recommending studies show a significant number of IGBC diagnosed histologically as missed by surgeons whereas the selective recommending studies show most of the histologically diagnosed IGBC already suspected by the surgeons intraoperative. When comparing the macroscopic details of the IGBC’s between routine and selective studies, we found that there was significant overlap. Most of the findings missed by the surgeons as suspicious in routine studies were suspected by the surgeons involved in selective histology recommending studies. Thereby, favouring selective histology and emphasizing the need for careful intraoperative macroscopy for suspecting IGBC. Conclusion: Selective Histological examination of cholecystectomy specimens can be preferred if a careful intraoperative macroscopic examination is done and patient risk factors are taken into consideration.     

Optimizing deep bone ablation by means of a microsecond Er:YAG laser and a novel water microjet irrigation system

The microsecond Er:YAG pulsed laser with a wavelength of λ = 2.94 μm has been widely used in the medical field, particularly for ablating dental tissues. Since bone and dental tissues have similar compositions, consisting of mineralized and rigid structures, the Er:YAG laser represents a promising tool for laserosteotomy applications. In this study, we explored the use of the Er:YAG laser for deep bone ablation, in an attempt to optimize its performance and identify its limitations. Tissue irrigation and the laser settings were optimized independently. We propose an automated irrigation feedback system capable of recognizing the temperature of the tissue and delivering water accordingly. The irrigation system used consists of a thin 50 μm diameter water jet. The water jet was able to penetrate deep into the crater during ablation, with a laminar flow length of 15 cm, ensuring the irrigation of deeper layers unreachable by conventional spray systems. Once the irrigation was optimized, ablation was considered independently of the irrigation water. In this way, we could better understand and adjust the laser parameters to suit our needs. We obtained line cuts as deep as 21 mm without causing any visible thermal damage to the surrounding tissue. The automated experimental setup proposed here has the potential to support deeper and faster ablation in laserosteotomy applications.