Incorporating Anti-racist Principles Throughout the Research Lifecycle: A Position Statement from the Society of General Internal Medicine (SGIM).

Biomedical research has advanced medicine but also contributed to widening racial and ethnic health inequities. Despite a growing acknowledgment of the need to incorporate anti-racist objectives into research, there remains a need for practical guidance for recognizing and addressing the influence of ingrained practices perpetuating racial harms, particularly for general internists. Through a review of the literature, and informed by the Research Lifecycle Framework, this position statement from the Society of General Internal Medicine presents a conceptual framework suggesting multi-level systemic changes and strategies for researchers to incorporate an anti-racist perspective throughout the research lifecycle. It begins with a clear assertion that race and ethnicity are socio-political constructs that have important consequences on health and health disparities through various forms of racism. Recommendations include leveraging a comprehensive approach to integrate anti-racist principles and acknowledging that racism, not race, drives health inequities. Individual researchers must acknowledge systemic racism's impact on health, engage in self-education to mitigate biases, hire diverse teams, and include historically excluded communities in research. Institutions must provide clear guidelines on the use of race and ethnicity in research, reject stigmatizing language, and invest in systemic commitments to diversity, equity, and anti-racism. National organizations must call for race-conscious research standards and training, and create measures to ensure accountability, establishing standards for race-conscious research for research funding. This position statement emphasizes our collective responsibility to combat systemic racism in research, and urges a transformative shift toward anti-racist practices throughout the research cycle.

Towards a Machine Learning Driven Trust Management Heuristic for the Internet of Vehicles.

The rapid proliferation of the emerging yet promising notion of the Internet-of-Vehicles (IoV) has led to the development of a variety of conventional trust assessment schemes to tackle insider attackers. The primary reliance of these frameworks is on the accumulation of individual trust attributes. While aggregating these influential parameters, weights are often associated with each individual attribute to reflect its impact on the final trust score. It is of paramount importance that such weights be precise to lead to an accurate trust assessment. Moreover, the value of the minimum acceptable trust threshold employed for the identification of dishonest vehicles needs to be carefully defined to avoid delayed or erroneous detection. This paper employs an IoT data set from CRAWDAD by suitably transforming it into an IoV format. This data set encompasses information regarding 18,226 interactions among 76 nodes, both honest and dishonest. First, the influencing parameters (i.e., packet delivery ratio, familiarity, timeliness and interaction frequency) were computed, and two feature matrices were formed. The first matrix (FM1) takes into account all the pairwise individual parameters as individual features, whereas the second matrix (FM2) considers the average of all pairwise computations performed for each individual parameter as one feature. Subsequently, unsupervised learning is employed to achieve the ground truth prior to applying supervised machine learning algorithms for classification purposes. It is worth noting that Subspace KNN yielded a perfect precision, recall, and the F1-score equal to 1 for individual parametric scores, whereas Subspace Discriminant returned an ideal precision, recall, and the F1-score equal to 1 for mean parametric scores. It is also evident from extensive simulations that FM2 yielded more accurate classification results compared to FM1. Furthermore, decision boundaries among honest and dishonest vehicles have also been computed for respective feature matrices.

MHC Ib molecule Qa-1 presents Mycobacterium tuberculosis peptide antigens to CD8+ T cells and contributes to protection against infection.

A number of nonclassical MHC Ib molecules recognizing distinct microbial antigens have been implicated in the immune response to Mycobacterium tuberculosis (Mtb). HLA-E has been identified to present numerous Mtb peptides to CD8+ T cells, with multiple HLA-E-restricted cytotoxic T lymphocyte (CTL) and regulatory T cell lines isolated from patients with active and latent tuberculosis (TB). In other disease models, HLA-E and its mouse homolog Qa-1 can act as antigen presenting molecules as well as regulators of the immune response. However, it is unclear what precise role(s) HLA-E/Qa-1 play in the immune response to Mtb. In this study, we found that murine Qa-1 can bind and present Mtb peptide antigens to CD8+ T effector cells during aerosol Mtb infection. Further, mice lacking Qa-1 (Qa-1-/-) were more susceptible to high-dose Mtb infection compared to wild-type controls, with higher bacterial burdens and increased mortality. The increased susceptibility of Qa-1-/- mice was associated with dysregulated T cells that were more activated and produced higher levels of pro-inflammatory cytokines. T cells from Qa-1-/- mice also had increased expression of inhibitory and apoptosis-associated cell surface markers such as CD94/NKG2A, KLRG1, PD-1, Fas-L, and CTLA-4. As such, they were more prone to cell death and had decreased capacity in promoting the killing of Mtb in infected macrophages. Lastly, comparing the immune responses of Qa-1 mutant knock-in mice deficient in either Qa-1-restricted CD8+ Tregs (Qa-1 D227K) or the inhibitory Qa-1-CD94/NKG2A interaction (Qa-1 R72A) with Qa-1-/- and wild-type controls indicated that both of these Qa-1-mediated mechanisms were involved in suppression of the immune response in Mtb infection. Our findings reveal that Qa-1 participates in the immune response to Mtb infection by presenting peptide antigens as well as regulating immune responses, resulting in more effective anti-Mtb immunity.

Nonclassical MHC Ib-restricted CD8+ T Cells Recognize Mycobacterium tuberculosis-Derived Protein Antigens and Contribute to Protection Against Infection.

MHC Ib-restricted CD8+ T cells have been implicated in host defense against Mycobacterium tuberculosis (Mtb) infection. However, the relative contribution of various MHC Ib-restricted T cell populations to anti-mycobacterial immunity remains elusive. In this study, we used mice that lack MHC Ia (Kb-/-Db-/-), MHC Ia/H2-M3 (Kb-/-Db-/-M3-/-), or ß2m (ß2m-/-) to study the role of M3-restricted and other MHC Ib-restricted T cells in immunity against Mtb. Unlike their dominant role in Listeria infection, we found that M3-restricted CD8+ T cells only represented a small proportion of the CD8+ T cells responding to Mtb infection. Non-M3, MHC Ib-restricted CD8+ T cells expanded preferentially in the lungs of Mtb-infected Kb-/-Db-/-M3-/- mice, exhibited polyfunctional capacities and conferred protection against Mtb. These MHC Ib-restricted CD8+ T cells recognized several Mtb-derived protein antigens at a higher frequency than MHC Ia-restricted CD8+ T cells. The presentation of Mtb antigens to MHC Ib-restricted CD8+ T cells was mostly ß2m-dependent but TAP-independent. Interestingly, a large proportion of Mtb-specific MHC Ib-restricted CD8+ T cells in Kb-/-Db-/-M3-/- mice were Qa-2-restricted while no considerable numbers of MR1 or CD1-restricted Mtb-specific CD8+ T cells were detected. Our findings indicate that nonclassical CD8+ T cells other than the known M3, CD1, and MR1-restricted CD8+ T cells contribute to host immune responses against Mtb infection. Targeting these MHC Ib-restricted CD8+ T cells would facilitate the design of better Mtb vaccines with broader coverage across MHC haplotypes due to the limited polymorphism of MHC class Ib molecules.

Lymphocytic choriomeningitis virus infection of dendritic cells interferes with TLR-induced IL-12/IL-23 cytokine production in an IL-10 independent manner.

Dendritic cells produce IL-12 and IL-23 in response to viral and bacterial infection and these cytokines are responsible for successful pathogen clearance. How sequential viral and bacterial infections affect the production of IL-12 and IL-23 is currently not known. Our study demonstrates that in dendritic cells infected with Lymphocytic choriomeningitis virus (LCMV), TLR activation with bacterial PAMPs resulted in reduced IL-12 and IL-23 expression compared to non-infected cells. Furthermore, expression of other proinflammatory cytokines, TNF-α and IL-6, were not inhibited under these conditions. We discovered that TLR-induced phosphorylation of p38 was significantly inhibited in LCMV-infected cells. We detected enhanced expression of suppressor of cytokine signalling (SOCS)-3 and IL-10. Yet, neutralizing IL-10 did not restore IL-12/IL-23 expression. Taken together, these results show that virus infection interferes with the magnitude of TLR-mediated inflammatory responses by repressing specific cytokine expression.

A Pulse Rate Estimation Algorithm Using PPG and Smartphone Camera.

The ubiquitous use and advancement in built-in smartphone sensors and the development in big data processing have been beneficial in several fields including healthcare. Among the basic vitals monitoring, pulse rate monitoring is the most important healthcare necessity. A multimedia video stream data acquired by built-in smartphone camera can be used to estimate it. In this paper, an algorithm that uses only smartphone camera as a sensor to estimate pulse rate using PhotoPlethysmograph (PPG) signals is proposed. The results obtained by the proposed algorithm are compared with the actual pulse rate and the maximum error found is 3 beats per minute. The standard deviation in percentage error and percentage accuracy is found to be 0.68 % whereas the average percentage error and percentage accuracy is found to be 1.98 % and 98.02 % respectively.

Mutation and protein expression analysis of CYP1A1 gene-a study on female breast cancer cases from India.

Increased risk may be associated with exposure to genotoxic agents during breast development because the undifferentiated ductal elements of breast are more susceptible to the action of genotoxic early in life and thus an impairment in Cytochrome P 4501A1 (CYP1A1) may contribute to the development of breast cancer. Therefore, we carried out the population-based study in a total of 105 Indian female breast cancer cases with equal normal adjacent controls. A total of 20 samples (20/105, 19.04 %) showed final mutations in the exon 7 of the CYP1A1 gene where 5 cases harbored frame shift mutation (deletion of G nucleotide), and the remaining were missense mutation observed in 15 cases of breast cancer with significant association to histological grade (chi square -7.20, p = 0.02), tumor stage (chi square -6.36, p = 0.01), menopausal stage (chi square -9.76, p = 0.001), and ER status (chi square -4.22, p = 0.03). We further did protein expression analysis of CYP1A1 through immunohistochemistry where 66 cases showed down or no expression (+) (66/105, 62.85 %), 28 cases with moderate expression (++) (28/105, 26.66 %), and 11 cases with high expression (+++) (11/105, 10.47 %). Highly significant associations were observed between protein expression and clinico-pathological variables like Her 2 category (chi square = 31.73, p < 0.0001) and tumor stage (chi square = 10.27, p = 0.005). Importantly, mutation(s) of the type like deletion of A nucleotide and missense mutation (Gly > Val) exclusively showed low (+) or no expression for the CYP1A1 protein when studied in relation to each other. In summary, CYP1A1 may be associated with breast cancer and its down regulation may serve as an important tool in the field of biomarker study.

Genetic polymorphisms of ESR1, ESR2, CYP17A1, and CYP19A1 and the risk of breast cancer: a case control study from North India.

Estrogen is a key driver of breast cancer and genes involved in its signaling and biosynthesis are crucial in breast cancer progression. In this study, we investigated the role of estrogen signaling and synthesis related genes polymorphism in susceptibility to breast cancer risk in North India population in a case-control approach. We examined the association of single nucleotide polymorphism (SNP) in estrogen receptors, ESR1 (rs2234693) and ESR2 (rs2987983); estrogen biosynthesis enzymes, CYP17A1 (rs743572); and aromatase, CYP19A1 (rs700519) with breast cancer risk. Cases (n = 360) were matched to controls (n = 360) by age, sex, ethnicity, and geographical location. Results provided evidence that all the genetic variants were significantly associated with breast cancer risk among North Indian women. Furthermore, on performing stratified analysis between breast cancer risk and different clinicopathological characteristics, we observed strong associations for menopausal status, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status, clinical stage, and histological grade. Our results suggest that these genes could be used as molecular markers to assess breast cancer susceptibility and predicting prognosis in North India population.

Association of mutation and hypermethylation of p21 gene with susceptibility to breast cancer: a study from north India.

p21 gene located at chromosome 6p21.2 is a possible tumour suppressor gene involved in the pathogenesis of breast cancer. Both genetic and epigenetic alterations in p21 have been implicated in breast carcinoma. In the present study, our main aim was to study the impact of these two kinds of alterations of p21 gene in Indian female breast cancer patients. A total of 150 female breast cancer patients of north India were screened by PCR-SSCP followed by direct sequencing and methylation specific PCR. Mutational screening of p21 gene revealed significant amount of mutations [32.66% (49/150)] in exon 2, whereas p21 promoter was found hypermethylated in 42 of 150 (28%) breast cancer patients in our population. The intriguing feature of the study was the G>T transition (GAG>TAG) at codon 107 and the A>C transition (AGC>CGC) at codon 146 possibly rendering p21 completely ineffective in its anti- proliferative activity. Our results suggest a significant association between the mutational and hypermethylation profile of p21 gene. Therefore, we show for the first time that the significant association of p21 mutation and hypermethylation leads to the complete inactivation of p21 gene in Indian female breast cancer patients. Complete silencing of the p21 gene seems to be the result not only of genetic alterations but also of epigenetic modification.

Iatrogenic Cerebrospinal Fluid Breast Augmentation: Rare Complication of Ventriculoperitoneal Shunts and Management Strategies.

BACKGROUND: Ventriculoperitoneal shunt is one of the most common neurosurgical procedures in the treatment of hydrocephalus. There are reports of migration of the distal catheter to the breast pocket where cerebrospinal fluid then collects and can develop into a pseudocyst. There exist case reports in the literature of patients with prior breast augmentation who present with distal catheter migration from the peritoneal space into the breast tissue. We present a case series of 3 patients with preexisting breast augmentation who returned with unilateral breast enlargement after ventriculoperitoneal shunt. In all 3 patients, the distal catheter migrated out of the peritoneal space and was found to be coiled around the breast prosthesis. Additionally, we offer recommendations for managing these complications and a review of the literature. METHODS: We performed a systematic review without meta-analysis of studies involving management of shunt migration in the setting of preexisting breast implants. We present a case series of 3 patients whom we treated with breast cerebrospinal pseudocyst after migration of the distal catheter into the breast tissue. RESULTS: A total of 17 studies, dating from 2002 to 2022, met our inclusion and exclusion criteria and were selected for full review. Catheter migration occurred between 2 weeks and 9 months of initial shunt placement. All patients presented with unilateral breast enlargement and cerebrospinal fluid pseudocyst formation. All patients underwent revision shunt surgery. Surgical treatment strategies used included reimplantation of the distal catheter into the pleural space or ipsilateral or contralateral peritoneal space or complete removal of the entire shunt system. CONCLUSIONS: Breast-related ventriculoperitoneal shunt complication is a rare entity that is increasingly seen as more patients receive breast augmentation. Breast-related shunt complications most commonly present with cerebrospinal fluid pseudocyst formation in the breast. It is important for neurosurgeons to be aware of an underlying breast implant before placing a ventriculoperitoneal shunt. For patients who have migration of the distal catheter into the breast, a protocol for managing these situations should be followed to ensure no shunt infection and avoidance of future catheter migration complications with subsequent shunt revisions.

CD8+ T cell immunodominance in lymphocytic choriomeningitis virus infection is modified in the presence of toll-like receptor agonists.

Currently, we have limited understanding of how Toll-like receptor (TLR) engagement by microbial products influences the immune response during a concurrent virus infection. In this study, we established that dual TLR2 plus TLR3 (designated TLR2+3) stimulation alters the immunodominance hierarchies of lymphocytic choriomeningitis virus (LCMV) epitopes by reducing NP396-specific CD8+ T cell responses and shifting it to a subdominant position. The shift in immunodominance occurred due to a reduction in antigen uptake and the reduced cross-presentation of NP396, a major LCMV immunodominant epitope that is efficiently cross-presented. Moreover, the altered immunodominance was dependent on TLR stimulation occurring at the site of infection. Finally, as lipopolysaccharide failed to induce the same phenomenon, the data suggest that these findings are dependent not only on the dual engagement of the TRIF/MyD88 pathways but also on how TLR agonists activate antigen-presenting cells. Taken together, our data demonstrate a novel role for TLR ligands in regulating antiviral CD8+ T cell responses due to the regulation of the cross-presentation of cell-associated antigens.

The TLR2 agonists lipoteichoic acid and Pam3CSK4 induce greater pro-inflammatory responses than inactivated Mycobacterium butyricum.

The innate immune system can recognize pathogen-associated molecular patterns (PAMP) through toll-like receptors (TLRs). TLR stimulation by TLR-ligands (TLR-L) induces several genes that can regulate the immune response. In this study, we compared the ability of diverse TLR2-L to activate professional antigen presenting cells (pAPCs). We found that in comparison to whole non-replicating microorganism Mycobacterium butyricum, the smaller components; lipoteichoic acid and Pam3CSK4 significantly enhanced the expression of several pro-inflammatory mediators. These included IL-6, TNF-α and nitric oxide both at the mRNA and the protein levels. Moreover, the higher response was associated with a differential activation of nuclear transcription factor kappa-B (NF-κB) by the diverse TLR2-L. However, all three ligands enhanced antigen cross-presentation and T cell induction after virus infection to the same extent. In conclusion, the data highlight the potential for small components of TLR agonists to induce superior inflammatory immune responses than whole microbial preparation in the field of vaccine studies.

Ocular Syphilis Mimicking Giant Cell Arteritis.

Syphilis is a rare cause of vision loss that mostly occurs after an infection of the meninges, brain tissue, and parenchyma. Syphilis can mimic auto-immune disease like giant cell arteritis which also manifest as sudden vision loss. Spirochete Treponema pallidum can spread through sexual contact and cause painless ulcers. Spirochetes can disseminate systemically and lead to secondary syphilis. Ocular syphilis can affect all parts of the eye in secondary and tertiary stages. It can present as scleritis, inflammation of the optic nerve, and uveitis. We present the case of a 59- year-old male suffering from severe vision loss in the left eye and headache initially misdiagnosed with giant cell arteritis. He was correctly diagnosed with ocular syphilis after seeing a red macular rash on palms and soles, and was given penicillin G and probenecid. His visual acuity and field of vision improved soon. Ocular syphilis is usually diagnosed late or misdiagnosed and leads to irreversible vision loss. Physicians should keep in mind the possibility of ocular syphilis in patients presenting with a sudden loss of vision and severe headaches.

Listeria delivers tetanus toxoid protein to pancreatic tumors and induces cancer cell death in mice.

Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease. Tumors are poorly immunogenic and immunosuppressive, preventing T cell activation in the tumor microenvironment. Here, we present a microbial-based immunotherapeutic treatment for selective delivery of an immunogenic tetanus toxoid protein (TT856-1313) into PDAC tumor cells by attenuated Listeria monocytogenes. This treatment reactivated preexisting TT-specific memory T cells to kill infected tumor cells in mice. Treatment of KrasG12D,p53R172H, Pdx1-Cre (KPC) mice with Listeria-TT resulted in TT accumulation inside tumor cells, attraction of TT-specific memory CD4 T cells to the tumor microenvironment, and production of perforin and granzyme B in tumors. Low doses of gemcitabine (GEM) increased immune effects of Listeria-TT, turning immunologically cold into hot tumors in mice. In vivo depletion of T cells from Listeria-TT + GEM-treated mice demonstrated a CD4 T cell-mediated reduction in tumor burden. CD4 T cells from TT-vaccinated mice were able to kill TT-expressing Panc-02 tumor cells in vitro. In addition, peritumoral lymph node-like structures were observed in close contact with pancreatic tumors in KPC mice treated with Listeria-TT or Listeria-TT + GEM. These structures displayed CD4 and CD8 T cells producing perforin and granzyme B. Whereas CD4 T cells efficiently infiltrated the KPC tumors, CD8 T cells did not. Listeria-TT + GEM treatment of KPC mice with advanced PDAC reduced tumor burden by 80% and metastases by 87% after treatment and increased survival by 40% compared to nontreated mice. These results suggest that Listeria-delivered recall antigens could be an alternative to neoantigen-mediated cancer immunotherapy.

Cross, but not direct, presentation of cell-associated virus antigens by spleen macrophages is influenced by their differentiation state.

The initiation of T-cell immune responses requires professional antigen-presenting cells. Emerging data point towards an important role for macrophages (Mphi) in the priming of naïve T cells. In this study we analyzed the efficiency and the mechanisms by which Mphi derived from spleen (Sp-Mphi) or bone marrow (BM-Mphi) present Lymphocytic choriomeningitis virus (LCMV) antigens to epitope-specific T cells. We demonstrate that because of phagosomal maturation, Sp-Mphi downregulate their ability to cross-present cell-associated, but not soluble, antigens, as they are further differentiated in culture without altering their capacity to directly present virus antigens after infection. We propose that Sp-Mphi are extremely efficient at direct and cross-presentation. However, if these cells undergo further M-CSF-dependent maturation, they will adapt to be more scavenger and phagocytic and concurrently reduce their cross-presenting capacity. Accordingly, Sp-Mphi can have an important role in regulating T-cell responses through cross-presentation depending on their differentiation state.

Effect of gender and age on the knowledge, attitude and practice regarding hepatitis B and C and vaccination status of hepatitis B among medical students of Karachi, Pakistan.

OBJECTIVES: To determine the vaccination status for hepatitis B and knowledge, attitude and practice (KAP) regarding hepatitis B and C among medical students of Karachi and to evaluate the effects of gender and age on the responses, regarding vaccination and KAP for Hepatitis B and C. METHODS: This cross sectional study was conductedin 7 medical colleges/universities of Karachi. Convenient sampling was used to collect the information. Questionnaire regarding awareness about prevention, transmission, diagnosis, treatment and vaccination availability for hepatitis B and C was completed from each individual. In addition, vaccination status of hepatitis B and the awareness of students regarding post exposure prophylaxis was also documented. One thousand five hundred and nine students participated in this study. RESULTS: The mean age of medical students (1509) was 20.35 +/- 1.72 years. Female participants were 1075 (71.2%) and 937 (62.1%) of the respondents were studying in public institutions. Eighty five percent of the respondents indicated that they were aware of availability of a vaccine for hepatitis B. Only 57.1% medical students showed excellent knowledge regarding the route of spread of hepatitis B and C. Students showing good knowledge of treatment procedures for hepatitis B and C were 48.2%. Half of the respondents (49.8%) showed good knowledge regarding spread of hepatitis by dental procedures. Seventy six percent of participating medical students did not have any knowledge about the post exposure prophylaxis for hepatitis B and C. Seventy four percent indicated that the hepatitis patients should not be isolated. Seventy nine percent of the students reported that they were vaccinated for hepatitis B and 70.6% of them were completely vaccinated (3 doses). About half of the respondents (49.4%) indicated that they were screened for hepatitis B and only 27.1% were screened for hepatitis C. Half of the students reported that they have had needle pricks in their students career. CONCLUSION: The overall KAP of studied group showed satisfactory outcomes. However, some areas of knowledge and attitude need to be modified or changed altogether.

Dependence of pathogen molecule-induced toll-like receptor activation and cell function on Neu1 sialidase.

The signaling pathways of mammalian Toll-like receptors (TLR) are well characterized, but the initial molecular mechanisms activated following ligand interactions with the receptors remain poorly defined. Here, we show a membrane controlling mechanism that is initiated by ligand binding to TLR-2, -3 and-4 to induce Neu1 sialidase activity within minutes in live primary bone marrow (BM) macrophage cells and macrophage and dendritic cell lines. Central to this process is that Neu1 and not Neu2,-3 and-4 forms a complex with TLR-2,-3 and-4 on the cell surface of naïve macrophage cells. Neuraminidase inhibitors BCX1827, 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (DANA), zanamivir and oseltamivir carboxylate have a limited significant inhibition of the LPS-induced sialidase activity in live BMC-2 macrophage cells but Tamiflu (oseltamivir phosphate) completely blocks this activity. Tamiflu inhibits LPS-induced sialidase activity in live BMC-2 cells with an IC(50) of 1.2 microM compared to an IC(50) of 1015 microM for its hydrolytic metabolite oseltamivir carboxylate. Tamiflu blockage of LPS-induced Neu1 sialidase activity is not affected in BMC-2 cells pretreated with anticarboxylesterase agent clopidogrel. Endotoxin LPS binding to TLR4 induces Neu1 with subsequent activation of NFkappaB and the production of nitric oxide and pro-inflammatory IL-6 and TNFalpha cytokines in primary and macrophage cell lines. Hypomorphic cathepsin A mice with a secondary Neu1 deficiency respond poorly to LPS-induced pro-inflammatory cytokines compared to the wild-type or hypomorphic cathepsin A with normal Neu1 mice. Our findings establish an unprecedented mechanism for pathogen molecule-induced TLR activation and cell function, which is critically dependent on Neu1 sialidase activity associated with TLR ligand treated live primary macrophage cells and macrophage and dendritic cell lines.

Yield of Muscle Biopsy in Patients with Findings of Myopathy on Electrodiagnostic Testing.

Background The evaluation of neuromuscular diseases includes detailed clinical assessment, blood testing, electrodiagnostic studies (EDS), biopsy, and genetic tests. EDS alone cannot provide a specific diagnosis. Further testing in the form of genetic tests or muscle biopsy (MB) is required. Objective The objective of the study is to evaluate the yield of MB in patients with findings of myopathy on electrodiagnostic testing and assess the factors affecting an abnormal biopsy outcome. Methods Electromyography (EMG)/nerve conduction studies (NCS) performed for suspected myopathy over 5 years from 2011 to 2016, at the neurophysiology department of a tertiary care center in Pakistan, were reviewed. Based on inclusion criteria, records of 58 patients were retrospectively reviewed. Results After an EMG/NCS diagnosis of myopathy, the frequency of MB testing was only 10.1%. The median age of patients was 26.5 years. The clinically suspected diagnosis was categorized into hereditary myopathy (n = 15, 25.9%) and acquired myopathy (n = 18, 31%). The positive predictive value of EMG is 77.2%. Twenty-eight (48.2%) patients had abnormal MB whereas 20 (34.4%) revealed normal findings. Factors significantly influencing an abnormal outcome of biopsy included moderate-to-severe elevation of creatine kinase (>2,000 U/L),presence of denervation changes, and severe myopathy on EMG. Conclusion Even though the overall yield of MB testing may not be very high in our setting due to the unavailability of special techniques and expertise, certain factors can help to improve the diagnostic yield. Clinicians should encourage MB testing, especially in cases with strong clinical, laboratory and electrodiagnostic suspicion, and absence of genetic testing for suspected myopathy.

Outcomes of patients with Guillain Barre Syndrome - Experience from a tertiary care hospital of a developing Asian country and review of regional literature.

Outcomes of Guillain Barre Syndrome (GBS), particularly those require mechanical ventilation have been reported from a number of Asian countries, albeit, scarcely from Pakistan. We conducted this study to determine the short-term outcomes of GBS and compare the results of mechanically ventilated and non-ventilated patients. Case records of patients admitted with GBS during 2011-2016 at a large tertiary care centre of Pakistan were retrospectively reviewed. 216 patients satisfying inclusion criteria were included. Patients were divided into 2 groups based on requirement of MV (MV and non-MV group). Short term outcomes were assessed by Modified Rankin Scale (MRS) at discharge, 2 weeks and 3 months and comparison done between MV and non-MV group. Outcome based on MRS score is categorized as good (MRS = 0-3) or poor (MRS = 4-6). Requirement for MV was noted in 24.5%. MV patients had severe weakness at presentation, longer length of hospital stay (LOS) and higher frequency of in-hospital complications. Overall mortality was 7.9%. Good outcomes at discharge and at 3 months were noted in significantly higher frequency in non-MV group (50.3% and 93.2% respectively) as compared to MV group (11.3% and 33.3% respectively). In MV group, increasing age, areflexia and longer LOS stay were found as independent predictors of poor outcome. Overall outcomes of GBS in our population are comparable to both regional and international studies. However, poor outcomes in MV group are seen in higher frequency in our study. Increasing age, areflexia and longer LOS may predict poor outcome in MV patients.

Drug-induced movement disorder and confusion associated with duloxetine.

A 60-year-old woman with major depressive disorder, developed high blood pressure, confusion and dyskinesias of face, neck and jaw, following an increase in her dose of duloxetine. Routine blood tests including toxic, infective and metabolic workup were unremarkable. Cerebrospinal fluid analysis and electroencephalogram were also normal. MRI brain showed bilaterally symmetrical diffusion-restricted areas in deep cerebral white matter. Duloxetine was held on suspicion of drug adverse effect. She had complete resolution of symptoms within 48 hours and resolution of MRI brain changes over 6 weeks. Serotonin norepinephrine reuptake inhibitors such as duloxetine may have the potential to cause drug-induced movement disorders, confusion and high blood pressure and should be used cautiously especially in elderly.