Neurovascular protection by targeting early blood–brain barrier disruption with neurotrophic factors after ischemia–reperfusion in rats

The ‘new penumbra'' concept imbues the transition between injury and repair at the neurovascular unit with profound implications for selecting the appropriate type and timing of neuroprotective interventions. In this conceptual study, we investigated the protective effects of pigment epithelium-derived factor (PEDF) and compared them with the properties of epidermal growth factor (EGF) in a rat model of ischemia–reperfusion injury. We initiated a delayed intervention 3 hours after reperfusion using equimolar amounts of PEDF and EGF. These agents were then administered intravenously for 4 hours following reperfusion after 1 hour of focal ischemia. Magnetic resonance imaging indices were characterized, and imaging was performed at multiple time points post reperfusion. PEDF and EGF reduced lesion volumes at all time points as observed on T₂-weighted images (T₂-LVs). In addition PEDF selectively attenuated lesion volume expansion at 48 hours after reperfusion and persistently modulated blood–brain barrier (BBB) permeability at all time points. Intervention with peptides is suspected to cause edema formation at distant regions. The observed T₂-LV reduction and BBB modulation by these trophic factors is probably mediated through a number of diverse mechanisms. A thorough evaluation of neurotrophins is still necessary to determine their time-dependent contributions against injury and their modulatory effects on repair after stroke.     

Reduced contribution of executive functions in impaired working memory performance in mild traumatic brain injury patients

Aim

Mild traumatic brain injury (MTBI) is associated with often selective impairment of both working memory (WM) and the executive functions (EFs). Research indicates that one of the commonest deficits present in MTBI patients falls in the domain of WM. We aimed to investigate the role of EFs in WM impairment following MTBI.

Methods

Performance on the tests of EFs and the verbal and visuo-spatial WM of 30 consecutive MTBI patients were compared with age/education/IQ matched 30 normal healthy control participants. Correlation between EFs and WM was studied separately for the MTBI and the control group.

Results

The MTBI and control group were tested on a range of EF tests and WM. The MTBI group was demonstrated impairment on verbal and visuo-spatial WM and category fluency tests only. Furthermore, the MTBI group had fewer significant correlations between the WM and EFs (5 out of 54 possible correlations) than in the control group (13 out of 54 possible correlations).

Conclusions

We suggest that MTBI may lead to WM deficits as the contribution of executive processes to support the WM is diminished following MTBI. Such an understanding of the poor WM performance in MTBI patients will be helpful when planning appropriate strategies for cognitive rehabilitation.     

Using Artificial Intelligence to Improve the Quality and Safety of Radiation Therapy

Within artificial intelligence, machine learning (ML) efforts in radiation oncology have augmented the transition from generalized to personalized treatment delivery. Although their impact on quality and safety of radiation therapy has been limited, they are increasingly being used throughout radiation therapy workflows. Various data-driven approaches have been used for outcome prediction, CT simulation, clinical decision support, knowledge-based planning, adaptive radiation therapy, plan validation, machine quality assurance, and process quality assurance; however, there are many challenges that need to be addressed with the creation and usage of ML algorithms as well as the interpretation and dissemination of findings. In this review, the authors present current applications of ML in radiation oncology quality and safety initiatives, discuss challenges faced by the radiation oncology community, and suggest future directions.     

A case of rhabdomyosarcoma masquerading as acute leukemia at presentation: a case report

Non-hematopoietic malignancies infiltrating bone marrow have always been a source of erroneous diagnosis. Among these, the small round cell tumors like neuroblastomas and rhabdomyosarcomas mimick the hematopoietic blasts. Several case reports of rhabdomyosarcoma mimicking acute leukemia, clinically and morphologically at presentation have been reported in the literature. To the best of our knowledge such an entity has not been reported in Indian literature. We report here one such case of alveolar rhabdomyosarcoma masquerading as acute leukemia. A thorough clinical examination with high degree of suspicion on bone marrow morphology and judicious use of appropriate immunohistochemistry markers will solve many of these cases.     

Enhanced selective cellular uptake and cytotoxicity of epidermal growth factor-conjugated liposomes containing curcumin on EGFR-overexpressed pancreatic cancer cells

Pancreatic cancer is one of the most malignant cancers with a high mortality rate. Some types of pancreatic cancer cells overexpress epidermal growth factor receptor (EGFR), which is a potential target for anticancer agents. In this study, we examined the effect of epidermal growth factor (EGF)-conjugated liposomes containing curcumin (EGF-LP-Cur) on three different EGFR-expressed human pancreatic cancer cell lines, BxPC-3, Panc-1 and Mia Paca-2. We have demonstrated that it is feasible to prepare liposomal vesicles of EGF-LP-Cur and that it is stable in the liquid vehicle at ambient conditions for three weeks. In addition, the formulation of curcumin had higher cytotoxicity on BxPC-3 than on any other cells. It is also shown that the cellular uptake of curcumin on BxPC-3, which is essential for the cytotoxicity, is associated with EGFR-mediated mechanism of action. In summary, our results have showed that targeting EGFR with EGF-conjugated curcumin liposomes enhanced the antitumor activity of curcumin against human pancreatic cancer cells.     

Daptomycin nonsusceptibility in Staphylococcus aureus with reduced vancomycin susceptibility is independent of alterations in MprF

A previous study documented the presence of mutations in mprF that accompanied the loss of daptomycin susceptibility among Staphylococcus aureus isolates following exposure to the drug. An association between the development of glycopeptide-intermediate S. aureus and daptomycin nonsusceptibility has also been recently described. We report that among three clinical S. aureus isolates which developed vancomycin heteroresistance, as well as daptomycin nonsusceptibility despite a lack of exposure to this drug, there were no mutations resulting in amino acid substitutions in MprF.     

Noonan syndrome: a case report

Noonan syndrome is a developmental disorder characterized by facial dysmorphia, short stature, cardiac defects and skeletal malformations. It may be sporadic or inherited as an autosomal dominant or recessive trait and occurs, one in 1,000-2,500 children. This is a case report of a 13 year-old girl who was referred by a general dental practitioner to a pediatric dentist for management. Full mouth dental rehabilitation was done and the child was brought to a dental institution for correction of orofacial and occlusal defects. Multidisciplinary treatment is the key to success in managing children with Noonan syndrome and the pediatric dentists play an important position to lead the health team.     

Spontaneous closure of midline diastema following frenectomy

Maxillary midline diastema is a common aesthetic problem in mixed and early permanent dentitions. The space can occur either as a transient malocclusion or created by developmental, pathological or iatrogenical factors. Many innovative therapies varying from restorative procedures such as composite build-up to surgery (frenectomies) and orthodontics are available. Although literature says every frenectomy procedure should be preceded by orthodontic treatment, we opted for frenectomy technique without any orthodontic intervention. Presented herewith is a case report of a 9-year-old girl with a high frenal attachment that had caused spacing of the maxillary central incisors. A spontaneous closure of the midline diastema was noted within 2 months following frenectomy. The patient was followed up for 4 months after which the space remained closed and there was no necessity for an orthodontic treatment at a later stage.     

Integrating binocular vision assessment in refractive surgery work-up: Proposition and protocol

Refractive surgeries are one of most commonly performed surgeries for correcting visual impairment due to refractive errors. With the increase in demand for refractive surgeries, there is an enormous strain on the operating surgeon for delivering ideal outcomes i.e 20/20 visual acuity. Regression, under-correction and ectasia are the most dreaded complications post-refractive correction, for the surgeon as well as the patient. They have significant effects on the quantity of the vision and most importantly on the quality of life of the patient. With the advent of digital era and jobs requiring the eyes being glued to the screen for hours there has been a surge in the patients presenting with complaints of asthenopia, glare, halos, and difficulty in focusing; pointing towards diagnosis of non-strabismic binocular vision anomalies (NSBVA). NSBVA in a postrefractive surgery patient may masquerade as regression or under-correction. However, timely diagnosis of NSBVA in such patients would prevent the greater harm caused by wrongful re-correction. Home- and office-based vision therapy results in improvement in visual acuity in a large majority of these patients. This preferred practice pattern intends to guide the refractive surgeons to diagnose and treat the postrefractive surgery NSBVA following a case-based and algorithmic approach. It also emphasizes the inclusion of the binocular vision assessment as a part of the pre-operative workup for patients undergoing refractive procedures.