A missense mutation disrupting a dibasic prohormone processing site in pro-opiomelanocortin (POMC) increases susceptibility to early-onset obesity through a novel molecular mechanism

The functional loss of both alleles of the human pro-opiomelanocortin (POMC) gene leads to a very rare syndrome of hypoadrenalism, red hair and early-onset obesity. In order to examine whether more subtle genetic variants in POMC might contribute to early-onset obesity, the coding region of the gene was sequenced in 262 Caucasian subjects with a history of severe obesity from childhood. Two children were found to be heterozygous for a missense mutation, R236G, which disrupts the dibasic cleavage site between beta melanocyte-stimulating hormone (beta-MSH) and beta-endorphin. Beta-TC3 cells transfected with the mutant POMC cDNA produced a mutant beta-MSH/beta-endorphin fusion protein. This fusion protein bound to the human melanocortin-4 receptor (hMC4R) with an affinity similar to its natural ligands, but had a markedly reduced ability to activate the receptor. This variant co-segregated with early-onset obesity over three generations in one family and was absent in 412 normal weight UK Caucasian controls. Combining the results in UK Caucasians with a new case-control study in French subjects and three previously published reports, mutations disrupting this processing site were present in 0.88% of subjects with early-onset obesity and 0.22% of normal-weight controls. These results suggest that the R236G mutation may confer an inherited susceptibility to obesity through the production of an aberrant fusion protein that has the capacity to interfere with central melanocortin signalling.     

Perceptions of recurrence risk and behavioural changes among first‐ever and recurrent stroke survivors: A qualitative analysis

BackgroundAmong stroke survivors, the risk of stroke recurrence is high, and stroke survivors'' perception of the risk of recurrence is crucial to promote healthy behaviours.ObjectivesThis study aimed to explore the perceptions of stroke survivors about their risk of recurrence and healthy behavioural modifications.DesignA qualitative interview study was carried out.ResultsWe interviewed 19 stroke survivors from 3 hospitals. Thematic analysis showed that the perceptions of recurrence risk and healthy behavioural changes differed between first‐ever and recurrent stroke survivors. Three themes were generated from the data of first‐ever stroke survivors: indifference to and unawareness of the risk of stroke recurrence, the need for professional information support and different awareness of the importance of different healthy behaviours. For first‐relapse stroke patients: worry but feel powerlessness towards recurrent event, accurate information is still warranted, regret of unhealthy behaviour patterns. For the survivors suffered two or more times recurrences: perceived severity of recurrences, increased psychological care need, incorrect perceptions of healthy behaviour.Discussion and ConclusionStroke survivors with or without recurrence hold different perceptions towards the risk of recurrence and behavioural changes. The need for information related to warning signs, recurrence risk and risk factors remained consistently unmet. The benefits of healthy behaviours could be a double‐edged sword for the prevention of stroke recurrence if the survivors fail to understand these accurately. It is strongly recommended that a specific recurrence risk communication tool and related health education plan be explored on the basis of the number of times patients have experienced stroke recurrence to inform secondary prevention of stroke in the future.Patient/Public ContributionThe patients were involved in the formulation of interview questions and conduct of this study. No public was involved in this study.     

The role of Pakistani dentists in tobacco cessation

Objective : To assess Pakistani dentists' ability, willingness and perceived barriers to carry out tobacco cessation activities for their patients in the dental office. The study is limited to the smoking form of tobacco use. Method : Using a structured questionnaire for a cross sectional study, 239 full time or part time practising licensed dentists based in Islamabad and Rawalpindi were recruited by two sampling techniques; convenience and cluster sampling. Participation rate was 66.2%. Result : Based on the characteristics, the study population is assumed representative of the average Pakistani dentist. Prevalence of smoking amongst dentists was 20.3%. Only one‐third rated their knowledge and ability regarding tobacco cessation messages as good/excellent. The majority of the dentists considered tobacco cessation activity as peripheral to their profession. The main barrier to performing tobacco cessation interventions was cited as gender. Conclusion : Dentists exhibit a superficial approach to delivery of smoking cessation care. It is recommended that dentists be trained in delivering effective tobacco dependence intervention, using the WHO/FDI advocacy guide for oral health professionals, modified to incorporate gender oriented culturally sensitive doctor‐patient interaction. Tobacco cessation clinics should also be set up in private and public sectors to augment the dentists' participation.     

A new reassortant clade 2.3.2.1a H5N1 highly pathogenic avian influenza virus causing recent outbreaks in ducks,geese, chickens and turkeys in Bangladesh

A total of 15 dead or sick birds from 13 clinical outbreaks of avian influenza in ducks, geese, chickens and turkeys in 2017 in Bangladesh were examined. The presence of H5N1 influenza A virus in the affected birds was detected by RT‐PCR. Phylogenetic analysis based on full‐length gene sequences of all eight gene segments revealed that these recent outbreaks were caused by a new reassortant of clade 2.3.2.1a H5N1 virus, which had been detected earlier in 2015 during surveillance in live bird markets (LBMs) and wet lands. This reassortant virus acquired PB2, PB1, PA, NP and NS genes from low pathogenic avian influenza viruses mostly of non‐H9N2 subtypes but retained HA, NA and M genes of the old clade 2.3.2.1a viruses. Nevertheless, the HA gene of these new viruses was 2.7% divergent from that of the old clade 2.3.2.1a viruses circulated in Bangladesh. Interestingly, similar reassortment events could be traced back in four 2.3.2.1a virus isolates of 2013 from backyard ducks. It suggests that this reassortant virus emerged in 2013, which took two years to be detected at a broader scale (i.e. in LBMs), another two years until it became widely spread in poultry and fully replaced the old viruses. Several mutations were detected in the recent Bangladeshi isolates, which are likely to influence possible phenotypic alterations such as increased mammalian adaptation, reduced susceptibility to antiviral agents and reduced host antiviral response.     

All-terrain vehicle injuries in children: injury patterns and prognostic implications

Background All-terrain vehicle (ATV) accidents are common in children. Our purpose was to identify imaging patterns associated with ATV injuries in children.Patients and methods The study group comprised 141 consecutive children admitted to a tertiary pediatric hospital following ATV accidents. Medical records were evaluated for demographics and patient outcome. All imaging studies were reviewed and abnormalities cataloged.Results Extremity fractures were the most common injuries in our study, occurring in 38% of patients. Lower extremity fractures were more common than upper extremity fractures. Partial foot amputation, an unusual injury, was present in three children. Torso injuries were present in 22% of the children. Pulmonary contusions, but not abdominal injuries, were significantly associated with long-term disability or death (p=0.01). Brain injuries occurred in 19% of the children and were significantly associated with death or long-term disability (p=<0.001). No association of brain injury and skull fracture was present.Conclusions A wide variety of injuries were identified in children with ATV accidents. Partial foot amputation, an unusual injury, was identified in three children. Brain injuries and lung contusions detected by computed tomography were associated with long-term disability and death. Radiologists need to be aware of injuries associated with ATV accidents.     

Healing potential of cream containing extract of Sphaeranthus indicus on dermal wounds in Guinea pigs

A cream containing ethanolic extract of aerial parts of Sphaeranthus indicus, Linn. (Asteraceae) was evaluated for wound healing activity in guinea pigs. The cream was applied in vivo on the paravertebral area of six excised wounded models once a day for 15 days. The cream significantly enhanced the rate of wound contraction and the period of epithelialization comparable to neomycin.     

Primary repair of an esophageal rupture using pleural flap

Esophageal perforation remains an important thoracic emergency. Aggressive operative therapy remains the mainstay for treatment. A case of esophageal perforation, consequent upon impacted food bolus, is presented. An 80 years old female, with multiple comorbidities, presented with dysphagia and right sided chest pain, who had a distal esophageal tear, secondary to accidental meat ball ingestion. Rigid esophagoscopy showed complete occlusion of the distal esophagus with a meat ball. Right thoracotomy was performed, which showed perforated esophagus with large meat ball protruding from it. Endoscopic removal of the food particles was done, and the rupture was repaired using a pleural flap. The entire postoperative stay was uneventful and the patient was discharged on the ninth post-operative day.     

Diagnosis and management of neoplastic lesions of the submandibular triangle

Review of submandibular triangle neoplasms (benign and malignant) treated at a tertiary referral centre in the United Kingdom (1986-2004). One hundred and seven cases identified via computerised search of histopathology records over the 18 year review period. Retrospective review clinical notes and collation with data maintained prospectively by the senior author. Forty nine benign and 58 malignant neoplasms of the submandibular triangle were reviewed. Definitive diagnosis was by excision and pathological examination. Pleomorphic adenoma (n=37) were the most common benign neoplasms. For malignant lesions (n=58), 48 were primary malignancies and 10 metastatic lesions. The most frequent primary lesions were malignant non-Hodgkin lymphoma (n=22), adenoid cystic carcinoma (n=9) and mucoepidermoid carcinoma (n=9). The mainstay treatment for both benign and malignant lesions was surgical either by extracapsular excision of the gland/lesion or selective levels I, IIa and III neck dissection. The main post-operative complication was temporary weakness of the marginal mandibular nerve (13%). Submandibular triangle neoplasms are rare and pose many diagnostic and therapeutic challenges. There is a relatively high incidence of malignant neoplasms in this region (54%). Benign tumours manifest a mild course of disease and have an excellent prognosis following adequate excision. Malignant tumours have a poor symptomatology that can result in late (often post-operative) diagnosis. The adequacy of primary surgery is crucial and would support the approach of a more radical excision primarily with a selective levels I, IIa and III neck dissection; ensuring a definitive operation for benign lesions, avoiding the risks of tumour spillage associated with a more limited excision; and removing the primary echelon of lymph nodes at risk of metastasis if the pathology in fact turns out to be malignant; without a significantly higher morbidity in comparison with an extracapsular gland/lesion excision.     

The diagnostic value of single photon-emission computed tomography bone scans combined with CT (SPECT-CT) in diseases of the foot and ankle

BackgroundA radionuclide bone scan with single photon-emission computed tomography and CT (SPECT-CT) is a new imaging modality which combines highly detailed CT with the functional information from a triple phase radionuclide bone scan. Little has been published about its diagnostic accuracy and usefulness in foot and ankle pathology. The aim of this study is to evaluate whether bone scans with SPECT-CT provide a useful contribution to the management of patients with foot and ankle pain, and whether it results in changes to clinical management.MethodsA retrospective study involving 50 patients was conducted between March 2010 and April 2011. SPECT-CT was requested in cases where definitive clinical diagnosis could not be achieved after clinical examination and plain radiography. Pathology as highlighted on SPECT-CT was taken as the definitive diagnosis in these patients and was treated accordingly. Patients were subsequently seen in the follow up clinic to evaluate the outcome of their treatment.ResultsIn 11 patients (22%), the provisional clinical diagnosis matched with the findings of the SPECT-CT and no change in treatment was necessary. In 39 patients (78%) the findings of the SPECT-CT did not correlate exactly with the initial clinical diagnosis and led to a modified treatment plan. The accuracy, sensitivity, specificity, positive predictive and negative predictive value of SPECT-CT in this series was 94%, 95.45%, 83.3%, 97.6% and 71.43% respectively.ConclusionsSPECT-CT is a useful investigation tool in foot and ankle pathologies. The present study shows a high diagnostic accuracy and we recommend its use in cases with diagnostic uncertainty.