Nonviral delivery of synthetic siRNAs in vivo

Sequence-specific gene silencing using small interfering RNA (siRNA) is a Nobel prize-winning technology that is now being evaluated in clinical trials as a potentially novel therapeutic strategy. This article provides an overview of the major pharmaceutical challenges facing siRNA therapeutics, focusing on the delivery strategies for synthetic siRNA duplexes in vivo, as this remains one of the most important issues to be resolved. This article also highlights the importance of understanding the genocompatibility/toxicogenomics of siRNA delivery reagents in terms of their impact on gene-silencing activity and specificity. Collectively, this information is essential for the selection of optimally acting siRNA delivery system combinations for the many proposed applications of RNA interference.     

Recapitulating lipid accumulation and related metabolic dysregulation in human liver-derived organoids

Journal of Molecular Medicine - Fatty liver disease has grown into a major global health burden, attributed to multi-factors including sedentary lifestyle, obesogenic diet and prevalence of...     

Desmoplastic medulloblastoma in a 48-year-old male

Medulloblastoma is a malignant invasive embryonal tumor of the cerebellum with preferential manifestation in children. The peak of occurrence is seven years of age. Seventy percent of medulloblastomas occur in individuals younger than 16. In adulthood, 80% of medulloblastomas arise in the 21-40 years age group. A 48-year-old male patient was admitted to the hospital with complains of headache, ataxia, morning vomiting and difficulty in speech was operated with the diagnosis of presence of mass of 4 x 7 cm size retaining a diffuse homogenous contrast in the posterior fossa. The diagnosis of desmoplastic medulloblastoma was given after histopathological examination. Immunohistochemical examination revealed that neoplastic cells showed staining with neuron-specific enolase and synaptophysin but not with glial fibrillary acidic protein. This lesion showed nodular, reticulin free-zones (pale islands) surrounded by densely packed, highly proliferative cells. The pale regions within the tumor did not contain reticulin fibers. Desmoplastic medulloblastoma is encountered especially in adulthood. This type of tumor rarely occurs beyond the fifth decade of life. We present a case of desmoplastic medulloblastoma in a 48-year-old male.     

Increased spasticity in a chronic spinal cord injury patient after scabies infestation: A case report

Spasticity is a common feature of spinal cord injury (SCI). Spasticity exacerbation is commonly encountered with nociceptive and exteroceptive stimuli including bladder and bowel dysfunction, pressure sores, contracture, tight-fitting leg bags and clothing, and ingrown toenail. This report describes a patient with chronic SCI (T4 level) who complained of increasing spasticity of bilateral lower extremities for 5 weeks. He also had skin lesions on different parts of his body, accompanied by itching above the spinal cord lesion level. A clinical diagnosis of scabies was made and pharmacologic treatment was initiated. Following treatment, spasticity was significantly reduced and the skin rash with itching faded out. This report is the first of scabies skin infestation lesions triggering exacerbation of spasticity in an SCI patient.     

Quantitative Doppler evaluation of the splenoportal venous system in various stages of cirrhosis: differences between right and left portal veins

PURPOSE: The purpose of our study was to evaluate the relationship between the splenoportal hemodynamics in patients with cirrhosis and the stage of the disease. METHODS: Patients with cirrhosis were grouped according to modified Child-Pugh scoring into stages A, B, and C of cirrhosis. A control group of healthy volunteers was included. After gastroenterologic clinical and laboratory examinations, all participants underwent a splenoportal Doppler sonographic evaluation in which the vessels' diameter, area, and blood flow velocity were measured and blood flow rate and the congestion index in the splenoportal venous system were calculated. RESULTS: Seventy-five patients with cirrhosis (25 women and 50 men) were enrolled; the control group consisted of 30 healthy volunteers (15 women and 15 men) with no liver disease. The mean age (+/- standard deviation) of the patients was 54.4 +/- 14.8 years (range, 13-80 years) and of the control subjects was 47.3 +/- 14.5 years (range, 18-72 years). No significant differences in vessel diameter, blood flow velocity, and blood flow rate were found in the main and left portal veins between the study group and the control group. In the right portal vein, we found decreases in the vessel diameter, blood flow velocity, and blood flow rate, and in the splenic vein, we found increases in vessel diameter and blood flow rate. The congestion index was increased in the main portal and splenic veins but was unchanged in the left portal vein. CONCLUSIONS: Although our data indicate that there is no difference in Doppler sonographic parameters of the main portal vein according to Child-Pugh scores, the hemodynamic differences between the left and right branches of the portal vein may be clinically useful in patients with cirrhosis.     

Managing aesthetic referrals in NHS Scotland: Outcomes from 1122 patients in the East of Scotland

The Adult Exceptional Aesthetic Referral Protocol (AEARP) encompasses a series of aesthetic procedures which, as they do not treat an underlying disease process, are not routinely available within the National Health Service. Provision of these services can only be provided on an exceptional basis.In this prospective study, we evaluated the referral process and outcomes of 1122 patients referred under the AEARP over a 3.5-year period. Referrals were screened by a vetting panel comprising of a plastic surgeon, clinical nurse specialist, and clinical psychologist. Following initial vetting, supported patients underwent psychological assessment. Patients supported by psychology were assessed in clinic, and if deemed clinically suitable, were offered surgery.Overall, 20% (225/1122) of referrals were supported for surgery. Following primary vetting, 57% (640/1,122) of referrals were supported, 40% (197/492) of referrals to clinical psychology were supported, and 65% (225/345) of the remaining cases referred for consultation were supported for surgery. Unsupported referrals included those not fulfilling the referral guidelines or those with contraindications.The AEARP is simple and effective to implement, and has been instrumental in streamlining the referral-to-outcome process in a centralised, transparent, and fair manner. It reduces a potential high number of clinic appointments where patients do not meet the aesthetic criteria and/or fail to attend – thereby helping to streamline other surgical pathways by improving clinic efficiency. Moreover, it aids referring clinicians and patient education around aesthetic issues including a holistic approach. Wide adoption of such standards may reduce waiting times, facilitate cost savings, and ultimately enhance patient outcomes.     

Neuroschistosomiasis mimicking lower back pain: case report of a rare differential diagnosis in a pediatric patient

Background

Spinal myelitis is an infrequent manifestation of spinal cord infection. It is caused by the Schistosoma species, which are endemic in South America, part of the Middle East, and Africa.

Case presentation

We report the case of a 13-year-old male adolescent complaining of progressive lower back pain and weakness of the lower extremities for 3 days. Initial magnetic resonance imaging revealed typical transverse myelitis. Subsequently, parasite serology showed a markedly elevated level of Schistosoma antibody titers, and cerebrospinal fluid analysis yielded normal results. Because of our presumptive diagnosis of neuroschistosomiasis, the patient was prescribed an empirical regimen of an anti-parasitic agent, after which his neurological deficit promptly subsided. The patient was followed for 1 year and showed a complete long-term resolution of symptoms.

Conclusions

This case highlights the increasing prevalence of neuroschistosomiasis in recent years, particularly in patients with a history of travel to endemic regions. Moreover, the study reports the clinicoradiological features of this enigmatic disorder. This rare occurrence potentiates further studies to address unanswered questions about neuroschistosomiasis.

     

Gingival health status in renal transplant recipients: relationship between systemic inflammation and atherosclerosis

Cardiovascular disease (CVD) is the leading cause of mortality in renal transplant recipients (RTR). Systemic and periodontal inflammation has been suggested to have a possible role in the development of atherosclerosis. In the present study, we aimed to investigate the relationship between gingival health status, inflammation and atherosclerosis in RTRs. Eighty‐three RTR (50 male, 33 female) were enrolled in the study. Routine biochemical analyses, serum lipoproteins, C‐reactive protein, fibrinogen, homocystein, parathyroid hormone (PTH) and cyclosporin A (CsA) trough levels were studied. All patients had 24‐h ambulatory blood pressure monitoring and B‐mode ultrasound of the common carotid arteries. Gingival status was evaluated by the Löe and Silness gingival index (GI). Mean GI value was 2.3 ± 0.5. Fifty patients (60.3%) had GI value ≥ 2.1 (severe gingivitis; group A). Thirty‐three patients (39.7%) had GI value < 2.1 (no or moderate gingivitis; group B). Age, carotid intima‐media thickness (CIMT) and mean time on dialysis before transplantation were significantly higher in group A than in B. Systemic inflammation markers were not different between group A and group B. Mean CIMT was positively correlated with GI (r = 0.425; p = 0.001) and negatively correlated with high‐density lipoprotein cholesterol (r = ?0.256; p = 0.023). After the correction for confounding variables, mean CIMT was still significantly correlated with GI (r = 0.376, p = 0.02). In RTR, gingival inflammation seems to be associated with CIMT in the absence of systemic inflammation. Thus, gingivitis may, in part, play a role in the development of systemic atherosclerosis without causing any aggravation in systemic inflammatory response.