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Osteoarthritis (OA) is one of the most common chronic diseases in the world. However, current treatment modalities mainly relieve pain and inhibit cartilage degradation, but do not promote cartilage regeneration. In this study, we show that G protein-coupled receptor class C group 5 member B (GPRC5B), an orphan G-protein-couple receptor, not only inhibits cartilage degradation, but also increases cartilage regeneration and thereby is protective against OA. We observed that Gprc5b deficient chondrocytes had an upregulation of cartilage catabolic gene expression, along with downregulation of anabolic genes in vitro. Furthermore, mice deficient in Gprc5b displayed a more severe OA phenotype in the destabilization of the medial meniscus (DMM) induced OA mouse model, with upregulation of cartilage catabolic factors and downregulation of anabolic factors, consistent with our in vitro findings. Overexpression of Gprc5b by lentiviral vectors alleviated the cartilage degeneration in DMM-induced OA mouse model by inhibiting cartilage degradation and promoting regeneration. We also assessed the molecular mechanisms downstream of Gprc5b that may mediate these observed effects and identify the role of protein kinase B (AKT)-mammalian target of rapamycin (mTOR)-autophagy signaling pathway. Thus, we demonstrate an integral role of GPRC5B in OA pathogenesis, and activation of GPRC5B has the potential in preventing the progression of OA.
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Background/Aims@#Endoscopic ultrasound-guided liver biopsy (EUS-LB) is an effective and safe method of procuring liver tissue. The aims of this study were to assess and compare the outcomes and tissue adequacy of a single-pass, single-actuation, wet suction technique between 19 G and 22 G needles in patients undergoing EUS-LB. @*Methods@#We performed a prospective case series study of 20 patients undergoing EUS-LB at a single center between September 2017 and April 2020. The primary objective was to evaluate differences in sample adequacy via a single actuation wet suction technique between a 19 G core needle and a 22 G core needle. Adequacy was gauged by cumulative core biopsy length and the number of portal tracts visualized. @*Results@#The 19 G needle provided a longer core length (2.5 cm vs. 1.2 cm, p<0.0001), more complete portal tracts (5.8 vs. 1.7, p<0.0001), more total tracts (8.8 vs. 3, p<0.0001), and a longer, intact, fragment length (0.75 cm vs. 0.32 cm, p<0.0006). The 19 G needle was superior in providing adequate (60% vs. 5%, p<0.001) and diagnostic pathologic samples (85% vs. 10%, p<0.001). @*Conclusions@#A single-pass, single-actuation, wet suction technique using a 19 G needle is superior to that using a 22 G needle for tissue acquisition and sample adequacy in EUS-LB.
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Background/Aims@#Endoscopic ultrasound-guided liver biopsy (EUS-LB) is an effective and safe method of procuring liver tissue. The aims of this study were to assess and compare the outcomes and tissue adequacy of a single-pass, single-actuation, wet suction technique between 19 G and 22 G needles in patients undergoing EUS-LB. @*Methods@#We performed a prospective case series study of 20 patients undergoing EUS-LB at a single center between September 2017 and April 2020. The primary objective was to evaluate differences in sample adequacy via a single actuation wet suction technique between a 19 G core needle and a 22 G core needle. Adequacy was gauged by cumulative core biopsy length and the number of portal tracts visualized. @*Results@#The 19 G needle provided a longer core length (2.5 cm vs. 1.2 cm, p<0.0001), more complete portal tracts (5.8 vs. 1.7, p<0.0001), more total tracts (8.8 vs. 3, p<0.0001), and a longer, intact, fragment length (0.75 cm vs. 0.32 cm, p<0.0006). The 19 G needle was superior in providing adequate (60% vs. 5%, p<0.001) and diagnostic pathologic samples (85% vs. 10%, p<0.001). @*Conclusions@#A single-pass, single-actuation, wet suction technique using a 19 G needle is superior to that using a 22 G needle for tissue acquisition and sample adequacy in EUS-LB.
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Purpose@#Carotid artery stenting (CAS) has evolved as a first-line therapeutic option for carotid revascularization in indicated patients for stroke prevention, but there is still a lack of data on its effect on cognitive function (CF), especially among Indian patients. To determine the effect of CAS on CF and to study the immediate and delayed complications of CAS in Indian patients. @*Materials and Methods@#This was a prospective, observational, single-center study. CF was assessed using Addenbrooke’s cognitive examination version III (ACE) before and 3 months after stenting. The demographic and clinical parameters were also assessed. A follow-up evaluation after 3 months was done to compare CF and to observe the occurrence of any complications. @*Results@#Out of 31 patients, 3 were lost to follow up. There were no immediate or delayed procedure-related complications. There was a statistically significant improvement in overall ACE score and memory before and after stenting. On subgroup analysis of those with and without strokes, there was a significant improvement in visuospatial function and mean ACE score. Those with left CAS had significant improvement in memory, visuospatial, language, and ACE scores than right CAS. @*Conclusion@#CAS was associated with significant improvement in CF in patients.
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Background: In Pakistan, literacy means 'the ability to read and write'. Mother's education is a stronger determinant of child survivorship. This study was carried out in order to determine the impact of mother's literacy on child health in terms of personal hygiene of child, nutritional status and vaccination status, and to compare the child health status of literate and non-literate mothers
Methods: It was a cross-sectional study carried out in Paediatric Unit, Ayub Teaching Hospital, Abbottabad, from Dec 2015 to Aug 2016. Data was collected using non probability sampling and analysed on SPSS-21. Frequencies and percentages were calculated for categorical variables like gender, residence, education, immunization and hygiene status, and Mean+/-SD were calculated for quantitative variables like age
Results: Among total 160 children, mothers of 48 [30%] children were completely uneducated. Nutrition status showed that 89 [55.6%] were of normal height for age while rest of them were having stunting of mild to severe categories. Immunization of 135 [84.4%] of the children was done as per their age. Regarding hygiene, clothing of 129 [80.6%] was clean, nails of 95 [59.4%] children were properly clean and trimmed, while hair hygiene of 119 [74.4%] children and dental hygiene of 109 [68.12%] children was well maintained. Majority of those whose immunization, nutrition, and hygiene status was maintained had educated mothers
Conclusion: Maternal literacy has a direct effect on the overall child health with respect to personal hygiene, nutritional and vaccination status
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The hepatic lobule is divided into three zones along the portal-central vein axis. Hepatocytes within each zone exhibit a distinctive gene expression profile that coordinates their metabolic compartmentalization. The zone-dependent heterogeneity of hepatocytes has been hypothesized to result from the differential degree of exposure to oxygen, nutrition and gut-derived toxins. In addition, the gradient of Wnt signaling that increases towards the central vein seen in rodent models is believed to play a critical role in shaping zonation. Furthermore, hepatic zonation is coupled to the site of the homeostatic renewal of hepatocytes. Despite its critical role, the regulatory mechanisms that determine the distinctive features of zonation and its relevance to humans are not well understood. The present study first conducted a comprehensive zone-dependent transcriptome analysis of normal human liver using laser capture microdissection. Upstream pathway analysis revealed the signatures of host responses to gut-derived toxins in the periportal zone, while both the canonical Wnt pathway and the xenobiotic response pathway govern the perivenular zone. Furthermore, we found that the hypoxic environment of the perivenular zone promotes Wnt11 expression in hepatocytes, which then regulates unique gene expression via activation of the non-canonical Wnt pathway. In summary, our study reports the comprehensive zonation-dependent transcriptome of the normal human liver. Our analysis revealed that the LPS response pathway shapes the characteristics of periportal hepatocytes. By contrast, the perivenular zone is regulated by a combination of three distinct pathways: the xenobiotic response pathway, canonical Wnt signaling, and hypoxia-induced noncanonical Wnt signaling.
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Background: Triple-negative breast cancer [TNBC] is a poor prognostic subset of breast cancer that lacks the benefit of specific targeted therapy
Materials and Methods: A prospective study of the clinical profile of triple negative breast cancer cases at a tertiary referral centre. The duration of the study period was 26 months and the median follow up period was ten months. A total of 111 invasive breast cancer patients were evaluated from 1st August 2009 to 31st October 2011. We examined TNBC patients with respect to clinicopathological parameters, adjuvant chemotherapy regimens and relapse free survival
Results: In our study, patients were young [median age at presentation, 47 yrs], premenopausal [54%], tumour size was discordant with lymph node positivity, the histology was predominantly intraductal carcinoma [90%], histological grade higher than two [90%]. Relapses were early and preferential visceral [32%] and CNS metastasises [11.7%]. 91% of patients were eligible for adjuvant therapy but only 80% of the patients could complete full course of adjuvant chemotherapy. Anthracycline-based regimens [43%], sequential anthracycline and taxane-based regimen [24%] and other regimes like CMF [13%] were used as adjuvant chemotherapy in eligible TNBC patients. Median relapse free survival in patients following adjuvant chemotherapy was around 10 months at last follow-up
Conclusions: Patients with TNBC have aggressive clinicopathological characteristics with early and higher rate of disease relapse and therefore derive inadequate benefit from current adjuvant chemotherapy. So, new treatment strategies in adjuvant chemotherapy for TNBC are needed
Subject(s)
Humans , Female , Adult , Middle Aged , Prognosis , Prospective Studies , Anthracyclines , Drug Therapy , Lymph Nodes , Carcinoma, Intraductal, NoninfiltratingABSTRACT
Experimental data suggest that triple-negative breast cancer [TNBC] may have increased sensitivity to platinum-based chemotherapy but there is lack of relevant clinical data. Clinical outcomes in patients with metastatic TNBC treated with Platinum-based chemotherapy were evaluated in this prospective study. 21 selected patients with metastatic TNBC presenting at GCRI during the study period from 1[st] August 2009 to 31[st] October 2011 formed the study group with median follow up period of 10 months. They were given palliative chemotherapy based upon prior adjuvant chemotherapy along with an additional platinum compound. Response rates, response duration and toxicities of platinum-based chemotherapy were recorded and analyzed. In evaluable TNBC patients, overall response rate and complete clinical response were 72% and 38% with median response duration of four months. Response could not be assessed in three patients due to patient refusal for evaluation, lost to follow up and toxicities. In three TNBC patients after completion of platinum based chemotherapy have early isolated CNS relapse with systemic disease in remission. Haematological adverse effects were febrile neutropenia in 19% of patients, and grade 3-4 neutropenia [9%] thrombocytopenia and anaemia [7%]. The main non-hematological adverse effects reported in the present study were peripheral neuropathy [14%] and severe emesis [9%]. The most common Platinum-based chemotherapy combination was carboplatin and paclitaxel in 11 patients [52%] of evaluable patients. Patients who received this regime have complete response rate, overall response rate and toxicity was 45%, 65% and 10%. TNBC patients with platinum-based chemotherapy have better overall response rates, higher complete clinical response rates, prolonged response duration and acceptable safety profile. The results of the present study need to be confirmed with a larger randomized study with a longer follow up
Subject(s)
Humans , Female , Platinum , Antineoplastic Agents , Neoplasm Metastasis , Tertiary Care Centers , Prospective Studies , CisplatinABSTRACT
We describe an extramedullary plasmacytoma of both breasts in a 35-year-old woman. No other Ivement was detected in the bone marrow or in any other site. Extramedullary plasmacytoma of breast are extremely rare, especially those that are not associated with multiple myeloma
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Continuously growing incisors are common to all rodents, which include the Microtus genus of voles. However, unlike many rodents, voles also possess continuously growing molars. Here, we report spontaneous molar defects in a population of Prairie voles (Microtus ochrogaster). We identified bilateral protuberances on the ventral surface of the mandible in several voles in our colony. In some cases, the protuberances broke through the cortical bone. The mandibular molars became exposed and infected, and the maxillary molars entered the cranial vault. Visualisation upon soft tissue removal and microcomputed tomography (microCT) analyses confirmed that the protuberances were caused by the overgrowth of the apical ends of the molar teeth. We speculate that the unrestricted growth of the molars was due to the misregulation of the molar dental stem cell niche. Further study of this molar phenotype may yield additional insight into stem cell regulation and the evolution and development of continuously growing teeth.
Subject(s)
Animals , Female , Humans , Male , Arvicolinae , Genetics , Molar , Diagnostic Imaging , Pedigree , X-Ray MicrotomographyABSTRACT
STUDY DESIGN: Prospective cohort study. PURPOSE: To assess whether additional implantation of Coflex following spinal decompression provided better clinical outcomes compared to decompression alone for symptomatic lumbar spinal stenosis (LSS) and to determine whether improvement in clinical outcomes correlated with changes in the radiological indices studied. OVERVIEW OF LITERATURE: Literature on benefits of additional Coflex implantation compared to decompression alone for symptomatic LSS is limited. METHODS: Patients with symptomatic LSS who met the study criteria were offered spinal decompression with Coflex implantation. Those patients who accepted Coflex implantation were placed in the Coflex group (n=22); while those opting for decompression alone, were placed in the comparison group (n=24). Clinical outcomes were assessed preoperatively, six-months, one-year and two-years postoperatively, using the Oswestry disability index, 100 mm visual analogue scale (VAS)-back pain and VAS-leg pain, and short form-36 (SF-36). Radiological indices (disc height, foraminal height and sagittal angle) were assessed preoperatively, six months, one year, and two years postoperatively. RESULTS: Both groups showed statistically significant (p<0.001) improvement in all the clinical outcome indicators at all points in time as compared to the preoperative status. However, improvement in the Coflex group was significantly greater (p<0.001) than the comparison group. Changes in the radiological indices did not correlate significantly with the improvement in clinical outcome indicators. CONCLUSIONS: Additional Coflex implantation after spinal decompression in symptomatic LSS offers better clinical outcomes than decompression alone in the short-term. Changes in radiological indices do not correlate with the improvements in clinical outcomes after surgery for symptomatic LSS.
Subject(s)
Humans , Cohort Studies , Decompression , Prospective Studies , Spinal StenosisABSTRACT
STUDY DESIGN: A prospective observational study. PURPOSE: To evaluate the role of nucleoplasty in the management of discogenic axial back pain; to determine the influence of concordant pain during provocative discography, annular tear and loss of disc height on the outcome of nucleoplasty. OVERVIEW OF LITERATURE: The role of nucleoplasty in the management of radicular leg pain due to disc herniation is known. However, the data regarding its role in the management of discogenic axial back pain is scarce. METHODS: A prospective evaluation of 30 patients with discogenic axial back pain undergoing nucleoplasty was performed. Pain, functional disability and quality of life were assessed using the 100 mm visual analogue scale (VAS), Oswestry Disability Index (ODI) and Short Form-36 (SF-36), respectively. RESULTS: The mean reduction in VAS was 31.03 and 29.03; mean reduction in ODI was 24.53 and 20.60; and mean increment in SF-36 was 13.58 and 12.30, at 6 months and at 12 months, respectively. The differences were statistically significant (p <0.05). Concordant pain during provocative discography, annular tear and loss of disc height did not affect a clinically significant improvement in any of the three outcomes (p =0.882, 0.213, and 0.170; respectively). CONCLUSIONS: Nucleoplasty produced statistically significant improvements in pain, functional disability and quality of life in patients with discogenic low back pain at 6 months and at 12 months. Concordant pain during provocative discography, annular tear and loss of disc height did not influence any of the outcomes after nucleoplasty in patients with discogenic axial back pain.
Subject(s)
Humans , Back Pain , Leg , Low Back Pain , Quality of LifeABSTRACT
Neonatal upper limb ischemia due to accidental arterial damage remains a major concern, which can lead to devastating complications if untreated. The primary objective of this case report is to emphasize the role of continuous infraclavicular brachial plexus block, the issues related with block performance in an ischemic hand, and the importance of ultrasound guidance in this particular case scenario. A 1.1 kg infant suffered from distal forearm ischemia due to accidental arterial damage, which was treated with brachial plexus block. An ultrasound-guided single shot block with 0.5 mL/kg of 0.25% bupivacaine was followed by ultrasound-guided catheter placement in the target area. A continuous infusion of 0.03% of bupivacaine at the rate of 0.5 mL/kg/hr [approx. 0.15 mg/kg/h of bupivacaine] was administered for 36 h. This treatment resulted in reversal of ischemia. Permanent ischemic damage was eventually confined to the tips of 4 fingers. We conclude that ultrasound-guided continuous infraclavicular block has a therapeutic role to play in the treatment of hand ischemia due to arterial damage and subsequent arterial spasm in neonates with added benefits
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New epidemics of infectious diseases often involve health care workers. In this short communication we present a case report of a health care professional who became the first case of influenza H1N1 virus to be notified in the United Arab Emirates. There are several issues related to workplace considerations and general public health, including preventive measures, the need for isolation of the patient, dealing with contacts, return to work, and communication with the workforce.
Subject(s)
Humans , Communicable Diseases , Delivery of Health Care , Disease Notification , Influenza A Virus, H1N1 Subtype , Influenza, Human , Occupational Health , Public Health , Return to Work , United Arab EmiratesABSTRACT
To provide community-based information on the prevalence of diabetes, hypertension and heart disease and to highlight their significant correlates. Data were collected in a cross-sectional household survey of 2,487 Kuwaiti nationals aged 50 and over in 2005/2006. A Proportionately representative sample of 1,451 respondents from a relatively more urban area [Capital] and 1,036 respondents from a relatively less urban area [Ahmadi] were interviewed. A proxy respondent was used in 5.4% of cases. Among the 2,605 potentially eligible persons approached, 2,487 [95.5%] participated. Doctor-diagnosed prevalences of hypertension, diabetes and heart disease in the two governorates were reported to be 53.4, 50.6 and 17.5%, respectively. If the prevalence in the two governorates is reflective of the nation, a remarkable increase seems to have occurred since 1996, The prevalence of each of the three diseases increased linearly by age among both sexes. Comorbidity of the three diseases increased from 3.6 to 9.4 and to 20.9% among those aged 50-59, 60-69 and >/= 70 years, respectively. Logistic regression showed the prevalence of chronic illnesses to be significantly higher among persons who were older, retired, non-Bedouin, less educated, had higher income, were less socially active, were obese and had poorer exercise behavior. The prevalence of diabetes and heart disease was significantly lower among women than men. Judging from data on two gavernorates, the prevalence of diabetes, hypertension and heart disease is likely to have increased to alarmingly high levels among older Kuwaitis, highlighting the need for focused intervention programs in order to reduce morbidity and increase healthy life years
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Diabetes Mellitus/epidemiology , Heart Diseases/epidemiology , Hypertension/epidemiology , Cross-Sectional Studies , Sex Distribution , Risk Assessment , PrevalenceABSTRACT
The authors present a rare case of anti-Vel antibodies in a patient who underwent a shoulder replacement with a custom designed procedure which involved combination of autologous blood pre-deposit, pre-operative haemodilution and resurfacing arthroplasty
Subject(s)
Humans , Shoulder , Blood Transfusion, Autologous , Hemodilution , Antibodies , ArthritisABSTRACT
This study was conducted in Khartoum Skin Teaching Hospital to determine the profile of the disease and the most common variant in the Sudan. The study included 50 patients [38 females and 12 males]. Pemphigus vulgaris was found to be the predominant variant in the Sudan [88%] as compared to pemphigus vegetans [12%]
Subject(s)
Humans , Male , Female , Hospitals, Teaching , SkinABSTRACT
Objective: To determine the etiological factors, complication[s] and prognosis of patients suffering from liver cirrhosis in our setup. Design: Cross-sectional study. Setting: Medical and surgical departments of Liaquat University Hospital Hyderabad/ Jamshoro, Sindh - Pakistan, from April 2005 to April 2007
Methods: Patients having an evidence of cirrhosis of liver on ultrasound examination of abdomen were enrolled. All those patients who were not confirmed to be cirrhotic, excluded from this study. All cases were studied to determine the etiological factors, complications and prognosis of disease. All data were recorded on a proforma. Patients with acute variceal hemorrhage were referred to surgical department for endoscopic sclerotherapy or variceal band ligation
Results: Total 100 patients were studied, 67[67%] males and 33[33%] females. Their mean age was 53.09 with SD= 8.85814 years. Majority of patients, 52[52%] had HCV infection, 16[16%] had HBV infection, 16[16%] had HBV and HCV co-infection, 08[08%] had alcohol abuse, 01[01%] had primary biliary cirrhosis, 02[02%] had Wilson's disease and no etiological factors were recorded in 05[05%] patients. Ascites was present in 59[59%] cases, portal hypertension in 42[42%], esophageal varices in 29[29%], spontaneous bacterial peritonitis in 29[29%], acute variceal hemorrhage in 27[27%], hepatic encephalopathy in different grades in 24[[24%], hepatorenal syndrome in 09[09%] and hepatocellular carcinoma in 07[07%] patients. All patients with acute variceal episode[s] were adequately and timely treated in surgical department. When cirrhotic patients were grouped into child-Pugh's classification, 37[37%] were in class 'A' category, 37[37%] in class 'B' category, and 26[26%] in class 'C' category
Conclusion: HCV infection is the major risk factor for cirrhosis in our setup. Ascites was the commonest complication. Patients with child-Pugh's class 'A' cirrhosis had significantly longer survival than patients with child-Pugh's class 'B' and 'C'. A multidisciplinary approach for prevention and control of ever increasing HCV infection must be adopted and to make the public awareness through the mass media about its drastic complications, and possible modes of its transmission
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Objective: To determine the frequency of night blindness among cirrhotic patients and evaluate the restoration of vision with vitamin A therapy. Design: - Case-control observational study. Setting: Medical ward of Liaquat University Hospital Hyderabad / Jamshoro, Sindh - Pakistan; from January 2006 to December 2007
Methods: Two hundred cirrhotic patients admitted at medical unit IV were enrolled in the study. The non-cirrhotic patients were excluded. Fifty healthy volunteers took part as the control subjects
Results: Out of 200 patient, 116[58%] were males and 84[42%] females. The mean age of the cirrhotic patients was 48.46 + 11.97 years. The cause of cirrhosis was hepatitis C virus in 146 [73%] cases, hepatitis B virus in 19[9.5%] cases, hepatitis C and B virus in 7[3.5%] cases, non B and C virus in 24[12%] cases and alcohol in 4[2%] cases. When cirrhotic patients were grouped into Child-Pugh's score, 44[22%] were in class A, 106 [53%] in class B and 50[25%] in class C. Among 200 patients, 122 [61%] had history of night blindness and 25[12.5%] had the colour blindness. Restoration of vision was observed in 105[86%] patients with vitamin A therapy [tablet Vitamin A 50,000 IU, Wilson Pharma], twice daily, for 6 weeks time
Conclusion: The history of night blindness and its restoration of vision with vitamin A therapy is a rough indicator of vitamin A deficiency in cirrhotic patients. The larger studies are required especially RBP [plasma retinol binding protein] and serum vitamin A concentration before recommendation of vitamin A replacement. The Ophthalmic changes in cirrhotic patients are preventable and treatable