Cardiovascular risk factors and carotid intima-media thickness with neurocognitive dysfunction in people living with HIV on stable combination anti-retroviral therapy.

The goal of this clinical research was to determine the relationship between carotid intima-media thickness (cIMT), cardiovascular risk factors, and neuro-cognitive function in people living with HIV (PLHIV) and were on stable combination anti-retroviral therapy (cART). This is a cross-sectional study performed at a single center, including 149 patients who visited the anti-retroviral therapy center of our tertiary care hospital. Among the PLHIV of our research, 62.4% had at least one associated cardiovascular risk factor, and 61.1% of them had abnormally high cIMT (≥ 0.9 mm on any one side, p = 0.035). These factors and being the male gender (p = 0.028) were associated with a greater Framingham 10-year risk percentage. Hypercholesterolemia was observed in 30.9% of the PLHIV and a higher body mass index (≥ 25 kg/m2) was found in 26.8% of them. The cognitive impairment was milder in 71.8% of cases and moderate in 9.4% of PLHIV. The Chi-square test revealed that a higher proportion of participants who had lower HDL-C levels (p = 0.045), smokers (p = 0.029), systolic blood pressure ≥ 140 mmHg (p = 0.012), and lower educational status (p = 0.017) had a poorer cognitive performance. In our sample population, a higher prevalence of elevated cIMT, cardiovascular risk factors, and mild and moderate cognitive deficiency was observed in PLHIV, who were on stable cART. However, routine assessment of the neuropsychological functions and management of modifiable risk factors are not performed in our patients. Further exploration of the relationship between cardiovascular risks, cIMT, and cognitive impairment in PLHIV is essential to formulate the guidelines and delay the onset of neurocognitive disorders in these patients.

Tumor-associated macrophage derived IL-6 enriches cancer stem cell population and promotes breast tumor progression via Stat-3 pathway.

BACKGROUND: Cancer stem cells (CSCs) play crucial role in tumor progression, drug resistance and relapse in various cancers. CSC niche is comprised of various stromal cell types including Tumor-associated macrophages (TAMs). Extrinsic ques derived from these cells help in maintenance of CSC phenotype. TAMs have versatile roles in tumor progression however their function in enrichment of CSC is poorly explored. METHODS: Mouse macrophages (RAW264.7) cells were activated by interaction with conditioned media (CM) of murine breast cancer cells (4T1) into TAMs and the effect of activated macrophage (TAM) derived factors was examined on enrichment of cancer stem cells (CSCs) and tumor growth using in vitro and in vivo models. RESULTS: In this study, we report that macrophages upon interaction with breast cancer cells activate tumor promoting function and exhibit differential expression of various proteins as shown by secretome analysis using proteomics studies. Based on secretome data, we found that Interleukin-6 (IL-6) is one of the up-regulated genes expressed in activated macrophages. Further, we confirm that TAMs produce high levels of IL-6 and breast cancer cell derived factors induce IL-6 production in activated macrophages via p38-MAPK pathway. Furthermore, we demonstrate that tumor activated macrophages induce enrichment of CSCs and expression of CSC specific transcription factors such as Sox-2, Oct-3/4 and Nanog in breast cancer cells. We further prove that TAM derived IL-6 plays a key role in TAM mediated CSC enrichment through activation of Signal transducer and activator of transcription 3 (STAT-3) signaling. TAM derived IL-6 influences breast cancer cell migration and angiogenesis. Moreover, our in vivo findings indicated that TAM derived IL-6 induces CSC population and resulting tumor growth in breast cancer. CONCLUSION: These finding provide evidence that TAM derived IL-6 plays a major role in CSC enrichment and tumor progression in breast cancer and IL-6 and its regulated signalling network may act as potential therapeutic target for management of breast cancer.

Primary adrenal plasmablastic lymphoma presenting as lymphomatous meningitis - A diagnostic perplexity.

A rare presentation of primary plasmablastic lymphoma (PBL) of the adrenal gland, as lymphomatous meningitis in a patient living with HIV.

Split cord malformation type 1 with two hemicord lesions.

Split cord malformations are rare entities which may present in an occult manner or in association with other lesions or congenital anomalies. Rarely, these cases may have associated hemicord lesions. We report an unusual case, the first of its kind, a type 1 split cord malformation with two pathologically different lesions (lipoma and dermoid) on one hemicord.

Minimizing complications associated with coronal approach by application of various modifications in surgical technique for treating facial trauma: A prospective study.

BACKGROUND: Coronal incision is a popular and versatile surgical approach to the anterior cranial vault and upper and middle third facial skeleton. The flap itself permits widespread exposure of the fractures in this region. The bicoronal flap was first described by Hartley and Kenyon (neurosurgeons) to gain access to the anterior cranium in 1907. It extension as an access flap to the upper and lateral aspect of the face was pioneered by Tessier (1971). Esthetically, it is pleasing as the surgical scar is hidden within the hair. AIMS: To evaluate the versatility of coronal incision using various modifications advocated in incision, exposure to fractured site, and closure of flap in treating the upper and middle third facial fractures. MATERIALS AND METHODS: A total of ten patients diagnosed with upper and middle third facial fractures requiring open reduction and internal fixation/correction of contour defect were selected after preoperative clinical and radiographic (computed tomography scan) evaluation. All the cases were operated by coronal approach to gain the access to the fracture/defect site for reduction/correction of the defect. Advantages and complication are evaluated. RESULTS: Excellent access and anatomical reduction by this approach with least number of complications; if it is performed with healthy knowledge of anatomy of the scalp and temporal region. Certain minimal complications have also been noted using various modifications used in the procedure. CONCLUSION: Despite of prolonged surgical time for the exposure, it is very advantages in treating upper and middle third facial fractures due to wide access and discreet scar (minimal).

A blast from the past!: The value of adding single slice magnetic resonance myelography sequence to magnetic resonance imaging of the spine; a flashback to the conventional myelography of the past.

BACKGROUND: The study was undertaken to determine whether a single slice magnetic resonance (MR) myelogram sequence improves the interpretation and diagnostic yield for magnetic resonance imaging (MRI) of the spine. METHODS: A total of 100 cases with positive findings were retrospectively reviewed. All patients had initial imaging with sagittal T1-weighted (T1-W) and T2-weighted (T2-W) scans, followed by axial T2-W images. Subsequently, a heavily T2-W single slice MR myelogram sequence was acquired in coronal and sagittal planes. The MR myelogram images were evaluated initially by a radiologist, and, further independently reviewed, by a neurologist, neurosurgeon, and spine surgeon. The utility of the MR myelogram in establishing the diagnosis was graded on a 4-point scale. RESULTS: Out of 100 cases, 53% showed degenerative spine or disc disease, 14% space occupying lesions, 13%, congenital lesions, 7% infection, and 7% other conditions. The MR myelogram contributed additional information in 50-74% cases. The intraclass correlation coefficient showed overall good agreement between observers in grading the utility of MR myelogram. CONCLUSION: Single slice MR myelography is noninvasive avoiding the complications associated with lumbar punctures/intrathecal contrast injections, while image acquisition takes only an added 6-8 s. Although MR myelogram has no value as a stand-alone sequence, its inherent advantage is that it completes the overview of the spinal pathology in entirety, and adds vital three-dimensional information in 50-74% of cases.

Synthesis of aryl-substituted naphthalene-linked pyrrolobenzodiazepine conjugates as potential anticancer agents with apoptosis-inducing ability.

A library of new aryl-substituted naphthalene C8-linked pyrrolo[2,1-c][1,4]benzodiazepine (PBD) conjugates with various linker architectures were designed, synthesized, and evaluated for their anticancer activity against a panel of 11 human cancer cell lines. All 32 conjugates show anticancer potential, with some of them exhibiting particularly high activity (0.01-0.19 µM). Thermal denaturation studies showed effective DNA binding capacity relative to DC-81. In assays for biological activity relating to cell-cycle distribution, these PBD conjugates induce G0/G1-phase arrest and also cause an increase in the levels of p53 and caspase-9 proteins, followed by apoptotic cell death. One conjugate in particular is the most promising candidate of the series, with the potential to be selected for further studies, either alone or in combination with existing anticancer therapies.