Evaluation of scleral incisions and their effects on corneal curvature in manual small-incision cataract surgery

Purpose:Incisions in cataract surgery can be modified in various ways in terms of size, shape, and axis to reduce or tailor astigmatism. This study was conducted to examine the effect of site (superior vs, temporal) and shape (frown vs. V-shaped, chevron) of scleral incisions for cataract surgery on corneal curvature.Methods:The prospective study was carried out on 200 consecutive patients with senile cataract and who were planned for surgery at a tertiary eye hospital in north India. The placement of the incision was decided by the steeper corneal meridian—whether superior or temporal—and then patients of these two groups were randomized for frown and V-shaped incision; in this way, four groups of 50 patients each were formed. Follow-up was done on day 1, at 2 weeks, 4 weeks, 8 weeks, and 12 weeks. At each follow-up, post-operative keratometry with routine postoperative examination was done. The results were statistically analyzed by using student’s t-test, Chi-squared test, and the Pearson correlation coefficient.Results:In all the four groups, the difference of preoperative astigmatism and surgically-induced astigmatism was statistically highly significant. The analysis of uncorrected visual acuity (UCVA) was statistically significant (P < 0.05) on postoperative day 1 and at 2, 4, and 12 postoperative weeks; it was statistically insignificant (P > 0.05) at postoperative week 8.Conclusion:Temporal incisions result in lesser postoperative surgically induced astigmatism (SIA) than superior incisions. Chevron incisions result in minimal change in corneal curvature. This effect can be utilized to tailor the postoperative astigmatism.     

PLGA-modified Syloid®-based microparticles for the ocular delivery of terconazole: in-vitro and in-vivo investigations

The eye is an invulnerable organ with intrinsic anatomical and physiological barriers, hindering the development of a pioneer ocular formulation. The aim of this work was to develop an efficient ocular delivery system that can augment the ocular bioavailability of the antifungal drug, terconazole. Mesoporous silica microparticles, Syloid^® 244 FP were utilized as the carrier system for terconazole. Preliminary studies were carried out using different drug:Syloid^® weight ratios. The optimum weight ratio was mixed with various concentrations (30 and 60%w/w) of poly (lactic-co-glycolic acid) (PLGA), ester or acid-capped and with different monomers-ratio (50:50 and 75:25) using the nano-spray dryer. Results revealed the superiority of drug:Syloid^® weight ratio of 1:2 in terms of yield percentage (Y%), SPAN and drug content percentage (DC%). Furthermore, incorporation of PLGA with lower glycolic acid monomer-ratio significantly increased Y%. In contrast, increasing the glycolic acid monomer-ratio resulted in higher DC% and release efficiency percentage (RE%). Additionally, doubling PLGA concentration significantly reduced Y%, DC%, drug loading percentage (DL%) and RE%. Applying desirability function in terms of increasing DC%, DL% besides RE% and decreasing SPAN, the selected formulation was chosen for DSC, XRD and SEM investigations. Results confirmed the successful loading of amorphized terconazole on PLGA-modified Syloid^® microparticles. Moreover, pharmacokinetic studies for the chosen formulation on male Albino rabbits’ eyes revealed a 2, 6.7 and 25.3-fold increase in mean residence time, C_max and AUC_0–24-values, respectively, compared to the drug suspension. PLGA-modified Syloid^® microparticles represent a potential option to augment the bioavailability of ocular drugs.     

Factors for Effective Identification of Patients at Nutritional Risk in Clinical Practice: Thematic Analysis of Qualitative Research

IntroductionDespite the high prevalence of malnutrition in patients at all levels of healthcare, early prevention and treatment of malnourished patients are often neglected and overlooked in clinical practice. The aim of this systematic literature review was to identify the factors considered most important by healthcare professionals in the identification and treatment of malnourished patients or those at risk of malnutrition.MethodsA systematic literature review of qualitative research was conducted. Documents published in scientific journals in English from 2011 to 2021 were searched in the PubMed (MEDLINE), CINAHL and ProQuest databases. The results were analysed with a thematic analysis of qualitative research findings.ResultsFrom the search set of 1010 results, 7 sources were included in the final analysis. Factors identified by health professionals as important in the identification and treatment of malnourished patients in clinical practice were grouped into five themes: unclear organizational structure; indefinite structure of nutritional care; poor continuity of nutritional care; lack of knowledge and skills of health professionals; lack of time and human resources.ConclusionsHealth policy must provide resources for nutritional care for patients at all levels of health care on the initiative of the highest professional bodies at the state level. To improve the nutritional care of patients in clinical practice, the management of health care institutions must promote and enable the professional and organizational establishment of clinical nutrition as a regular medical activity of the institution, develop clinical nutritional pathways, and promote evidence-based clinical practice and interprofessional collaboration.     

Clinical significance of IL-18, IL-15, IL-12 and TNF-α measurement in rheumatoid arthritis

The aim of the study was to evaluate the clinical significance of serum (S) and synovial fluid (SF) interleukin (IL)-18, IL-15, IL-12 and the tumor necrosis factor alpha (TNF-α) measurements in relation to laboratory and clinical measures of disease activity of patients with active rheumatoid arthritis (RA). Sixty-four patients with RA and 25 patients with osteoarthritis (OA) were included in this study. RA activity was determined using the Disease Activity Score (DAS) 28 index. Concentrations of IL-18, IL-15, IL-12 and TNF-α were measured by ELISA. Serum C-reactive protein (CRP) levels were also determined. Cross-sectional correlations between S and SF levels of cytokines and values of DAS 28 index were calculated. The results have shown that IL-18, IL-15, IL-12 and TNF-α levels in S and SF of patients with RA were significantly higher than the levels obtain from patients with OA (p<0.01). Significantly higher levels of IL-18, IL-15 and TNF-α were found in the SF compared to the S of patients with RA (p<0.01). Significantly higher S and SF levels of all four cytokines and serum CRP values were found in RA patients with high disease activity (DAS 28>5.1) compared to those with mild (DAS 28>3.2) and low disease activity (DAS 28>2.6) (p<0.01). Serum and SF concentrations of all four cytokines positively correlated with DAS 28 index values, i.e., disease activity. A poor correlation was found for S and SF IL-12 whereas the highest coefficient of correlation was found for SF IL-18 (r=0.879, p<0.01), and SF TNF-α (r=0.827, p<0.01) and disease activity in this study. Strong correlation was found between SF TNF-α and SF IL-18 levels (r=0.732, p<0.01). In conclusion, SF IL-18 and TNF-α levels in RA patients are good indicators of disease activity. The results obtained support the use of the DAS in clinical practice as a reliable method in assessing disease activity in RA patients.     

Unusual eosinophilic variant of chromophobe cell renal carcinoma--an ultrastructural diagnosis

A case of eosinophilic variant of chromophobe cell renal carcinoma (EVCCRC), an uncommon variety of renal cell carcinoma, occurred in a 72 year old male. The most problematic differential diagnosis was renal oncocytoma, as the two entities share overlapping features on histology, yet differ completely in biological behavior. EVCCRC is a potentially malignant neoplasm whereas renal oncocytoma is totally benign. Staining with Hale's Colloidal Iron using modified Mowry's technique showed granular cytoplasmic positivity. The diagnosis was confirmed by ultrastructural examination of the tumor which revealed unique features of EVCCRC like presence of numerous cytoplasmic microvesicles along with mitochondria displaying tubulo-vesicular cristae. This case delineates the role of electron microscopic examination as the sole means to differentiate EVCCRC from renal oncocytomas.     

Diagnostic approach to neurotransmitter monoamine disorders: experience from clinical,biochemical, and genetic profiles

Background and aim

To improve the diagnostic work-up of patients with diverse neurological diseases, we have elaborated specific clinical and CSF neurotransmitter patterns.

Methods

Neurotransmitter determinations in CSF from 1200 patients revealed abnormal values in 228 (19%) cases. In 54/228 (24%) patients, a final diagnosis was identified.

Results

We have reported primary (30/54, 56%) and secondary (24/54, 44%) monoamine neurotransmitter disorders. For primary deficiencies, the most frequently mutated gene was DDC (n = 9), and the others included PAH with neuropsychiatric features (n = 4), PTS (n = 5), QDPR (n = 3), SR (n = 1), and TH (n = 1). We have also identified mutations in SLC6A3, FOXG1 (n = 1 of each), MTHFR (n = 3), FOLR1, and MTHFD (n = 1 of each), for dopamine transporter, neuronal development, and folate metabolism disorders, respectively. For secondary deficiencies, we have identified POLG (n = 3), ACSF3 (n = 1), NFU1, and SDHD (n = 1 of each), playing a role in mitochondrial function. Other mutated genes included: ADAR, RNASEH2B, RNASET2, SLC7A2-IT1 A/B lncRNA, and EXOSC3 involved in nuclear and cytoplasmic metabolism; RanBP2 and CASK implicated in post-traductional and scaffolding modifications; SLC6A19 regulating amino acid transport; MTM1, KCNQ2 (n = 2), and ATP1A3 playing a role in nerve cell electrophysiological state. Chromosome abnormalities, del(8)(p23)/dup(12) (p23) (n = 1), del(6)(q21) (n = 1), dup(17)(p13.3) (n = 1), and non-genetic etiologies (n = 3) were also identified.

Conclusion

We have classified the final 54 diagnoses in 11 distinctive biochemical profiles and described them through 20 clinical features. To identify the specific molecular cause of abnormal NT profiles, (targeted) genomics might be used, to improve diagnosis and allow early treatment of complex and rare neurological genetic diseases.

     

Apoptotic signaling pathway activated by Helicobacter pylori infection and increase of apoptosis-inducing activity under serum-starved conditions

The enhanced gastric epithelial cell apoptosis observed during infection with Helicobacter pylori has been suggested to be of significance in the etiology of gastritis, peptic ulcers, and neoplasia. To investigate the cell death signaling induced by H. pylori infection, human gastric epithelial cells were incubated with H. pylori for up to 72 h. H. pylori infection induced the activation of caspase -8, -9, and -3 and the expression of the proapoptotic Bcl-2 family proteins Bad and Bid. The peak of the activity of the caspases occurred at 24 h. At this time, the inhibition of caspase-8 or -9 almost completely suppressed H. pylori-induced apoptosis. Inhibition of caspase-8 suppressed the expression of Bad and Bid and the subsequent activation of caspase-9 and -3. These observations indicate that H. pylori induces apoptosis through a pathway involving the sequential induction of apical caspase-8 activity, the proapoptotic proteins Bad and Bid, caspase-9 activity, and effector caspase-3 activity. Activation of the pathway was independent of CagA or vacuolating toxin. A membrane fraction of H. pylori was sufficient to activate this pathway, and treatment with proteinase K eliminated the activity. Apoptotic activity of the membrane fraction was significantly increased by incubating the bacteria under serum-starved conditions for 24 h. These observations suggest that environmental conditions in the human stomach could induce H. pylori-mediated pathogenesis, leading to a variety of clinical outcomes.     

Mixed medullary and follicular cell carcinoma of the thyroid with lymph node metastasis in a 7-year-old child

A 7-year-old boy presented with midline swelling in the neck. On fine-needle aspiration cytology it was diagnosed as papillary carcinoma of the thyroid. The patient underwent total thyroidectomy. Histopathological examination, immunohistochemistry and electron microscopy revealed the presence of two intermingled components: medullary carcinoma and papillary carcinoma. One of the submandibular lymph nodes had metastasis of both the components. The case was diagnosed as 'mixed medullary and follicular cell carcinoma' with papillary carcinoma pattern and lymph node metastasis. Mixed medullary and follicular cell carcinoma with intermingling of medullary and papillary carcinoma components is a rare tumor. In adults, only eight such cases with lymph node metastasis have been published. To the best of the authors' knowledge no pediatric case has previously been reported in the English-language literature.