Outcomes following KRASG12C inhibitor treatment in patients with KRASG12C-mutated solid tumors: A systematic review and meta-analysis.

OBJECTIVE: To assess the efficacy and safety of FDA-approved KRASG12C inhibitors in patients with KRASG12C-mutated solid tumors. METHODS: We searched PubMed, EMBASE, Cochrane Library, and major international conferences for clinical trials published in English up to March 6, 2023. Clinical trials investigating sotorasib or adagrasib and reporting the clinical outcomes of the objective response rate (ORR), disease control rate (DCR), or incidence rate of grade ≥ 3 adverse events (AEs) were eligible. The primary endpoint was the ORR. Secondary endpoints included the DCR, incidence rate of grade ≥ 3 AEs, and odds ratio (OR) of the ORR between patients with or without co-mutation. The Random-effects model was applied for the outcomes of interest. RESULTS: 18 studies with 1224 patients were included in this meta-analysis. The pooled ORR, DCR, and incidence rate of grade ≥ 3 AEs were 31 % (95 % CI, 25-37 %), 86 % (95 % CI, 82-89 %), and 29 % (95 % CI, 23-36 %), respectively. KRASG12C-mutated NSCLC patients with a co-mutation of KEAP1 exhibited a worse ORR than those with wild-type KEAP1 (OR: 0.35, 95 % CI: 0.16-0.77). CONCLUSIONS: This study provided a comprehensive understanding of the efficacy and safety of KRASG12C inhibitors in treating solid tumors and identified KEAP1 mutation as a potential predictive biomarker of inferior response in patients treated with KRASG12C inhibitors. These findings may assist in the design of future clinical trials for identifying populations that may benefit from KRASG12C inhibitor treatment.

[Correlation between intestinal toxicity and composition changes of toxic parts from Euphorbia ebracteolata before and after Terminalia chebula soup processing].

This study aims to explore the correlation between intestinal toxicity and composition changes of Euphorbia ebracteolata before and after Terminalia chebula soup(TCS) processing. Intragastric administration was performed on the whole animal model. By using fecal water content, inflammatory causes, and pathological damage of different parts of the intestinal tract of mice as indexes, the differences in intestinal toxicity of dichloromethane extraction of raw E. ebracteolata(REDE), dichloromethane extraction of TCS, and dichloromethane extraction of E. ebracteolata after simulated TCS processing(STREDE) were compared, so as to investigate the effect of TCS processing on the intestinal toxicity of E. ebracteolata. At the same time, the component databases of E. ebracteolata and T. chebula were constructed, and the composition changes of diterpenoids, tannins, and phenolic acids in the three extracted parts were analyzed by HPLC-TOF-MS. HPLC was used to compare the content of four diterpenoids including ent-11α-hydroxyabicta-8(14), 13(15)-dien-16, 12-olide(HAO), jolkinolide B(JNB), fischeria A(FA), and jolkinolide E(JNE) in the E. ebracteolata before and after processing and the residue of container wall after processing, so as to investigate the effect of TCS processing on the content and structure of the diterpenoids. The results showed that the REDE group could significantly increase the fecal water content and the release levels of TNF-α and IL-1ß from each intestinal segment, and intestinal tissue damage was accompanied by significant infiltration of inflammatory cells. However, compared with the REDE group, the intestinal tissue damage in the STREDE group was alleviated, and the infiltration of inflammatory cells decreased. The intestinal toxicity significantly decreased. Mass spectrometry analysis showed that there was no significant difference in the content of diterpenoids of REDE before and after simulated TCS processing, but a large number of tannins and phenolic acids were added. The results of HPLC showed that the content of four diterpenoids of E. ebracteo-lata decreased to varying degrees after TCS processing, ranging from-0.35% to-19.74%, and the decreased part mainly remained in the container wall, indicating that the structure of toxic diterpenoids of E. ebracteolata was not changed after TCS processing. The antagonistic effect of tannic and phenolic acids in the TCS may be the main reason for the reduced intestinal toxicity of E. ebracteolata after TCS processing. The TCS processing for E. ebracteolata is scientific.

Zone-addressable 20 × 20 940 nm VCSEL array with a 5-bit binary number pattern.

This article presents a monolithically zone-addressable 20 × 20 940 nm vertical-cavity surface-emitting laser (VCSEL) array with a binary number pattern design for sensing applications. The emitters in this VCSEL array have a uniquely designed binary pattern design, with each row representing a 5-bit pattern designed to aid pattern-matching algorithms to deduce the shape and depth information efficiently. Approximately 200 VCSELs are arranged in four individually addressable light-emitting zones, with ∼50 emitters in each zone. Each zone generates laser pulses up to 7.2 W in peak power.

Non-Hodgkin's Lymphoma with Intraspinal Involvement Mimics Bilateral Thoracolumbar Plexopath.

PURPOSE: Non-Hodgkin lymphoma (NHL) is the most common type of lymphoma, and its extranodal manifestation is rare. Skeletal muscle involvement is noted in only 1.1% of patients with NHL. Here, we present a case of high-grade B-cell lymphoma (HGBL); it infiltrated the left neural foramina from the left psoas muscle before encroaching on the whole spinal canal and subsequently invading the contralateral neural foramina from T12 to L3. CASE REPORT: A 43-year-old man with HGBL who could function independently presented with numbness and weakness of the left thigh 2 months after a diagnosis of infiltrative lymphoma in the left psoas muscle. His symptoms were urine incontinence and unsteady gait. A neurological examination revealed weakness in the left psoas and quadriceps with hyporeflexia and hypesthesia. Lumbar spine magnetic resonance imaging (MRI) revealed intraspinal extradural invasion from T12 to L3 with multiple left-sided root compression despite the resolution of primary psoas lymphoma. At 6 weeks after symptom onset, his symptoms progressed to weakness, numbness, and hyporeflexia of the bilateral lower extremities with preserved anal sensation. Follow- up MRI revealed the progression of intraspinal invasion, which spread through the spinal canal and invaded the contralateral neural foramina from T12 to L3. The patient was finally bound to a wheelchair. CONCLUSION: Clinicians must check for possible intraspinal involvement in patients with HGBL, particularly patients with known paraspinal soft-tissue involvement. The resolved infiltration of the soft tissue does not preclude the possibility of further neurological involvement. Additionally, MRI may provide higher resolution findings for clarifying the structure of the neural foramina and thecal sac. Keyword: Non-Hodgkin's Lymphoma, high-grade B-cell lymphoma, plexopathy.

Cefepime Induced Neurotoxicity Mimicking Clinical Presentation of Left Middle Cerebral Artery Infarction: A Case Report and Review of Literature.

PURPOSE: Cefepime is a widely used antibiotic which was known to have neurotoxicity resulted from its ability to cross the blood-brain barrier and a wide variety of symptoms had been documented. Here we reported a case of Cefepime induced neurotoxicity with rare presentation. The aim of this study was to improve the knowledge of this condition. CASE REPORT: A 89-year-old female with a history of ESRD (end stage renal disease) and superimposed acute cholecystitis was treated with Cefepime. She developed the symptoms of global aphasia, right hemiplegia, leftward eye deviation and abnormal plantar reflex at right foot, which resembled acute ischemic stroke at left MCA (middle cerebral artery), on the fourth day of Cefepime treatment. There was no evidence of acute infarction in MRI (magnetic resonance imaging) of brain and EEG (electroencephalography) revealed NCSE (nonconvulsive status epilepticus). NCSE was suspected to be attributed to Cefepime-induced neurotoxicity. The patient's main risk factors were decreased renal clearance and incorrect dosing. Conslusion: Cefepime-induced neurotoxicity should be suspected in patients who developed neurologic symptoms after the administration of Cefepime. Emergent image study for excluding more commonly seen or critical etiologies and further evaluation with EEG were necessary. For those patients who have risk factors for Cefepime neurotoxicity, such as ESRD, TDM (therapeutic drug monitoring) may be useful in providing close monitoring and preventing adverse effects associated with Cefepime treatment. Keyword: Cefepime, acute ischemic stroke, aphaia, nonconvulsive status epilepticus.

[Simulated processing with vinegar changes chemical structures of main terpenoids in Euphorbiae Ebracteolatae Radix].

This study aims to explore the chemical structure transformation mechanisms of the main terpenoids in the effective fraction of Euphorbiae Ebracteolatae Radix(EER) during the processing with vinegar. The terpenoids including ent-11α-hydroxyabicta-8(14),13(15)-dien-16,12-olide(HAO), jolkinolide B(JNB), fischeria A(FA), and eupractenoid A(EA) were heated at 160 ℃ with 6% acetic acid for 40 min, and then LC-MS/MS was employed to analyze the structural transformation rules of the terpenoids. Further, we analyzed the changes in the relative content of the four compounds and their transformation products in raw and vinegar processed EER to verify the transformation rules during the simulated processing with vinegar. In addition, JNB and FA were processed with single heating, heating with water or heating with acetic acid. We then employed HPLC to compare the content of these two terpenoids and their transformation products before and after processing, so as to investigate the effect of different processing methods on chemical structure transformation. The results showed that the lactone ring of the abietane-type diterpenoids HAO and JNB and the norditerpene lactone FA were opened by heating with acetic acid. When there were hydroxyl groups in the structures, terpenoids were esterized to esters and oxidized to form carbonyl groups. When there was epoxy ring in the structures, ring opening reaction was easy to occur. During the heating with acetic acid, the heterodimeric diterpenoid EA underwent the cleavage of ether bond to produce the rosane-type diterpenoid euphebracteolatin A(EHTA) and another abietane-type diterpenoid. The changes in the relative content of terpenoids and their transformation products in raw and vinegar-processed EER were basically consistent with those of simulated processing of components with vinegar. The HPLC results revealed that the effect of different simulated processing methods on structural transformation varied. Heating with acid can change JNB and FA into new components. Heating with water can also promote the structural transformation, with the efficiency obviously lower than that of heating with acid. Direct heating had no influence on the structure of JNB, while it significantly reduced the relative content of FA. The components treated with direct heating did not produce the products like those of the heating with acid. These results indicated that vinegar plays a key role in the structural transformation of diterpenoids during the processing of EER with vinegar. The structural transformation of diterpenoids in EER during the processing with vinegar may be the material basis for vinegar processed EER to reduce toxicity and preserve effect.

Downregulation of DPF3 promotes the proliferation and motility of breast cancer cells through activating JAK2/STAT3 signaling.

It is reported that the genetic variation of DPF3 is a risk factor of breast cancer through large-scale association research. However, the expression, function and mechanism in breast cancer is unknown. We applied qPCR and western blotting to detect the levels of DPF3 in breast cancer tissues. MTT and Anchorage-independent growth ability assay were used to evaluate the effect of DPF3 on cell proliferation. Wound healing and transwell invasion assay were performed to detect the role of DPF3 on cell motility ability. Herein, we found that the mRNA and protein levels of DPF3 are both significantly downregulated in breast cancer tissues. And downregulation of DPF3 can promote the proliferation and motility of breast cancer cells. Further investigation illustrated that downregulation of DPF3 can activate the JAK2/STAT3 signaling. In conclusion, we found that the downregulation of DPF3 plays an indispensable function in the progression of breast cancer, and may be served as a novel therapeutic target to therapy breast cancer.

Molecular epidemiology of canine parvovirus type 2 in Vietnam from November 2016 to February 2018.

BACKGROUND: Canine parvovirus type 2 (CPV-2) was first identified in the late 1970s; it causes intestinal hemorrhage with severe bloody diarrhea in kennels and dog shelters worldwide. Since its emergence, CPV-2 has been replaced with new genetic variants (CPV-2a, CPV-2b, and CPV-2c). Currently, information about the genotype prevalence of CPV-2 in Vietnam is limited. In the present study, we investigated the genotype prevalence and distribution of CPV-2 in the three regions of Vietnam. METHODS: Rectal swabs were collected from 260 dogs with suspected CPV-2 infection from northern, central, and southern Vietnam from November 2016 to February 2018. All samples were identified as parvovirus positive by real-time PCR, and further genotyping was performed using a SimpleProbe® real-time PCR assay. RESULTS: Of the 260 Vietnamese CPV-2 isolates, 6 isolates (2.31%) were identified as CPV-2a, 251 isolates (96.54%) were identified as CPV-2c and 3 isolates (1.15%) were untypable using the SimpleProbe® real-time PCR assay. In northern Vietnam, the percentages of CPV-2a and CPV-2c were 2.97% (3/101) and 97.3% (98/101), respectively. In central Vietnam, the percentages of CPV-2a and CPV-2c were 1.11% (1/90) and 98.89% (89/90), respectively. In southern Vietnam, the percentages of CPV-2a and CPV-2c were 3.03% (2/66) and 96.97% (64/66), respectively. CPV-2b was not observed in this study. The VP2 genes of CPV-2c in Vietnam are more genetically similar to those of CPV-2c strains in China and Taiwan than to those of prototype CPV-2c strains (FJ222821) or the first Vietnamese CPV-2c (AB120727). CONCLUSION: The present study provides evidence that CPV-2c is the most prevalent variant in Vietnam. Phylogenetic analysis demonstrated that the recent Vietnamese CPV-2c isolates share a common evolutionary origin with Asian CPV-2c strains.

Conjugated polymer/nanocrystal nanocomposites for renewable energy applications in photovoltaics and photocatalysis.

Conjugated polymer/nanocrystal composites have attracted much attention for use in renewable energy applications because of their versatile and synergistic optical and electronic properties. Upon absorbing photons, charge separation occurs in the nanocrystals, generating electrons and holes for photocurrent flow or reduction/oxidation (redox) reactions under proper conditions. Incorporating these nanocrystals into conjugated polymers can complement the visible light absorption range of the polymers for photovoltaics applications or allow the polymers to sensitize or immobilize the nanocrystals for photocatalysis. Here, the current developments of conjugated polymer/nanocrystal nanocomposites for bulk heterojunction-type photovoltaics incorporating Cd- and Pb-based nanocrystals or quantum dots are reviewed. The effects of manipulating the organic ligands and the concentration of the nanocrystal precursor, critical factors that affect the shape and aggregation of the nanocrystals, are also discussed. In the conclusion, the mechanisms through which conjugated polymers can sensitize semiconductor nanocrystals (TiO2 , ZnO) to ensure efficient charge separation, as well as how they can support immobilized nanocrystals for use in photocatalysis, are addressed.

Common Spontaneous Tumors and Tumor-like Lesions in 70 Pet Rodents and Negative MMTV Detection in Mammary Tumors.

Compared to the number of studies on the neoplasms of laboratory rodents, fewer studies have focused on spontaneous neoplasms in pet rodents. Notably, the mouse mammary tumor virus (MMTV) is associated with mammary tumors in rodents. In this study, 77 tumors and tumor-like lesions of biopsy samples were collected from 70 pet rodents, including hamsters (n = 47), guinea pigs (n = 16), unknown species (n = 4), rats (n = 2), and a gerbil. Fifty tumors were collected from 47 hamsters, in which the most common tumors were mammary tumors (13/50), followed by fibrosarcoma (9/50), mast cell tumors (4/50), and squamous cell carcinoma (4/50). The collected subtypes of mammary tumors in hamsters included tubular carcinoma (n = 5), tubular adenoma (n = 4), carcinoma and malignant myoepithelioma (n = 1), simple tubular carcinoma (n = 1), adenosquamous carcinoma (n = 1), and tubulopapillary adenoma (n = 1). In addition, twenty tumors were collected from guinea pigs, in which the most common tumor was lipoma (6/20), followed by adenocarcinoma of the mammary gland (4/20), trichofolliculoma (2/20), and collagenous hamartomas (2/20). In guinea pigs, the subtypes of mammary gland tumors were tubular carcinoma (n = 2), tubular and solid carcinoma (n = 1), and tubulopapillary carcinoma (n = 1). In 20 cases of mammary tumors, MMTV was not detected, implicating no evidence of MMTV infection in mammary oncogenesis in pet rodents in Taiwan.

Efficacy and Safety of Anti-Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Antibodies Plus Chemotherapy as First-Line Treatment for NSCLC in the People's Republic of China: a Systematic Review and Meta-Analysis.

Introduction: The available approved anticancer drugs for Chinese patients are relatively limited because of China's low participation rate in international clinical trials. Therefore, a focus on approved anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) drugs in China is needed. This study aims to assess the heterogeneity of anti-PD-1/PD-L1 antibodies manufactured in China (domestic PD-1/PD-L1) and overseas (imported PD-1/PD-L1) when combined with chemotherapy as the first-line treatment of NSCLC. Methods: A systematic search was performed using PubMed, EMBASE, and Cochrane Library of publications up to July 13, 2023. Meta-analysis was applied to compare the efficacy and safety profile between anti-PD-1/PD-L1 antibodies plus chemotherapy (PD-1/PD-L1+Chemo) and chemotherapy alone using STATA software. Pooled hazard ratios for progression-free survival and overall survival, odds ratios for objective response rate, and incidence rate of grade greater than or equal to three treatment-related adverse events with 95% confidence intervals were calculated in the domestic group and imported group by a random-effects model, and the heterogeneity between the two estimates was assessed. Results: There were 14 eligible clinical studies with a total of 3951 patients involved in this analysis, including eight studies of domestic PD-1/PD-L1+Chemo and six studies of imported PD-1/PD-L1+Chemo. The study revealed that there was no significant difference between domestic and imported PD-1/PD-L1+Chemo in overall survival (p = 0.80), progression-free survival (p = 0.53), and incidence rate of grade greater than or equal to three treatment-related adverse events (p = 0.10). Nevertheless, the objective response rate of imported PD-1/PD-L1+Chemo was significantly higher than that of domestic PD-1/PD-L1+Chemo (p = 0.03). Conclusions: Domestic anti-PD-1/PD-L1 antibodies plus chemotherapy were found to have comparable efficacy and safety to those combined with imported anti-PD-1/PD-L1 antibodies based on current evidence.

Hospitalized children with COVID-19 infection during large outbreak of SARS-CoV-2 Omicron strain: a retrospective study in Chaozhou, Guangdong, China.

OBJECTIVE: We aimed to investigate the clinical findings of hospitalized paediatric COVID-19 patients by the end of 2022. METHOD: All confirmed children with COVID-19 infection admitted into Chaozhou Central Hospital during the COVID-19 outbreak from 19 December 2022 to 1 February 2023 were included. Detailed clinical data of those children were evaluated retrospectively. RESULTS: A total of 286 children, ranging in age from 1 month to 13 years old, were diagnosed with SARS-CoV-2 infection. Among these cases, 138 (48.3%) were categorized as mild, 126 (44.0%) as moderate and 22 (7.7%) as severe/critical. Symptoms varied among the children and included fever, upper respiratory tract symptoms, convulsions, sore throat, poor appetite, dyspnoea and gastrointestinal symptoms. Notably, febrile convulsions were observed in 96 (33.6%) patients, while acute laryngitis was documented in 50 (17.5%) cases. Among the severe/critical patients, eight developed multisystem inflammatory syndrome in children (MIS-C), and tragically, one patient's condition worsened and resulted in death. Furthermore, MRI scans revealed abnormal brain signals in six severe/critical patients. The severe/critical group also exhibited more pronounced laboratory abnormalities, including decreased haemoglobin and elevated ALT, AST, LDH and CK levels. CONCLUSIONS: Febrile convulsions and acute laryngitis are frequently observed in children diagnosed with SARS-CoV-2 Omicron infection. Moreover, MIS-C and abnormal neuroimaging appear to be relatively common phenomena in severe/critical cases.

Antimicrobial resistance profile in Salmonella enterica serovar Choleraesuis isolates from diseased pigs in Taiwan.

This study investigated antimicrobial resistance in Salmonella enterica serovar Choleraesuis (S. Choleraesuis) isolates from diseased pigs in Taiwan (2015-2020). Among 272 isolates, florfenicol (96.7%), enrofloxacin (96.3%), doxycycline (91.2%), gentamicin (84.6%), and tiamulin (80.5%) exhibited high resistance. 99.3% of the isolates were resistant to at least one antibiotic, and 97.8% of the isolates were multidrug resistant. This study illustrated that S. Choleraesuis isolates exhibited high resistance to antimicrobials currently used in the Taiwanese swine industry.

Comparison of viremia of type II porcine reproductive and respiratory syndrome virus in naturally infected pigs by zip nucleic acid probe-based real-time PCR.

BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is a RNA virus with high genetic variation. This virus causes significant economic losses in most pig-producing countries. The clinical presentation of PRRSV ranges from asymptomatic to devastating. In this study, we developed a sensitive and specific zip nucleic acid probe-based real-time PCR assay to evaluate the viremia of natural PRRSV-infected pigs in Taiwan. Serum samples were collected from 577 pigs aged 5-12 weeks. These include 444 clinically healthy pigs and 133 symptomatic pigs were confirmed to have porcine respiratory disease complex (PRDC). RESULTS: Viremia was quantified in 79 of the 444 (17.8%) clinically healthy pigs and in 112 of the 133 (84.2%) PRDC cases. Viremias were significantly more common in pigs with PRDC compared with the clinically healthy pigs (P <0.0001). These results suggest that a high viral load is a major feature of PRRSV-affected pigs. CONCLUSIONS: ZNA probe-based real-time PCR can be a useful tool to diagnose symptomatic and asymptomatic PRRSV-infected pigs. The presence of this marker in a sample of animals with high PRRSV loads (>10(4.2) PRRSV genomes/µl of serum) seems to indicate that it correlates with the presence of PRDC in pigs.

Associations between frontal lobe activity and depressive symptoms in patients with major depressive disorder receiving rTMS treatment: a near-infrared spectroscopy study.

Introduction: The effects of repetitive transcranial magnetic stimulation (rTMS) on the left dorsolateral prefrontal cortex (DLPFC) in patients with major depressive disorder (MDD) have been proved to have antidepressant effects. However, the absence of biomarkers to assess treatment response remains a challenge. This research aims to explore the relationship between frontal lobe activity, measured using near infrared spectroscopy (NIRS), and changes in symptoms among MDD patients following rTMS treatment. Methods: A total of 26 MDD patients underwent 20 sessions of 10 Hz rTMS targeting the left DLPFC. NIRS was used to measure frontal lobe activity during a verbal fluency test at baseline, after 10 rTMS sessions, and after 20 rTMS sessions. Responders were defined as individuals with more than a 50% reduction in symptoms based on the 21-item Hamilton Depression Rating Scale after 20 rTMS sessions. Results: Among the 14 responders, an increase in frontal lobe activity was significantly correlated with improvements in depressive symptoms following 10 (p = 0.0001) and 20 rTMS sessions (p = 0.007). Additionally, frontal lobe activity after 10 rTMS sessions was significantly associated with symptom improvement after 20 sessions (p = 0.001). These associations were not observed among non-responders. Conclusion: The findings from this study indicate distinct patterns of frontal lobe activity between responders and non-responders to rTMS treatment, suggesting that NIRS has the potential to serve as a biomarker for monitoring treatment response in MDD patients undergoing rTMS.

NIRS-aided differential diagnosis among patients with major depressive disorder, bipolar disorder, and schizophrenia.

BACKGROUND: To establish a clinically applicable neuroimaging-guided diagnostic support system that uses near-infrared spectroscopy (NIRS) for differential diagnosis at the individual level among major depressive disorder (MDD), bipolar disorder (BPD), and schizophrenia (SZ). METHODS: A total of 192 participants were recruited, including 40 patients with MDD, 38 patients with BPD, 65 patients with SZ, and 49 healthy individuals. We analyzed the spatiotemporal characteristics of hemodynamic responses in the frontotemporal cortex during a verbal fluency test (VFT) measured by NIRS to assess the accuracy of single-subject classification for differential diagnosis among the three psychiatric disorders. The optimal threshold of the frontal centroid value (54 seconds) was utilized on the basis of the findings of the Japanese study. RESULTS: The application of the optimal threshold of the frontal centroid value (54 seconds) allowed for the accurate differentiation of patients with unipolar MDD (72.5%) from BPD (78.9%) or SZ (84.6%). CONCLUSION: These results suggest that the NIRS-aided differential diagnosis of major psychiatric disorders can be a promising biomarker in Taiwan. Future multi-site studies are needed to validate our findings.

Case Report: Late-Onset Mitochondrial Disease Uncovered by Metformin Use in a Patient With Acute Verbal Auditory Agnosia.

Introduction: Verbal auditory agnosia is rarely caused by mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. Lactate acidosis, which is the adverse effect of metformin, has proposed links to mitochondrial dysfunction and may trigger clinical features of mitochondrial diseases. Case Presentation: A 43-year-old right-handed man presented to our emergency department with acute onset fever and headache accompanied by impaired hearing comprehension. He could communicate well through handwritten notes but could not understand what others were saying. He had been diagnosed as having diabetes mellitus 2 months prior to this event. Vildagliptin 100 mg/day and metformin 1,700 mg/day were prescribed for glucose control. Laboratory tests revealed elevated lactate levels in serum and cerebrospinal fluid of the patient. Brain MRI disclosed bilateral temporal lesions. Acute encephalitis with temporal involved was initially diagnosed and acyclovir was given empirically. However, follow-up MRI after acyclovir treatment revealed a progression of prior lesions. Further mitochondrial genome analysis revealed a mitochondrial DNA point mutation at position 3,243 (m.3243A > G) with 25% heteroplasmy, which is compatible with MELAS. His clinical symptoms and serum lactate levels were improved after discontinuing the metformin use. Conclusions: To our knowledge, this is the first report of a patient having late-onset MELAS syndrome that manifested as acute verbal auditory agnosia, which was identified after the patient began using metformin. Metformin is known to inhibit mitochondrial function and could trigger clinical features of MELAS syndrome. We encourage clinicians to maintain a high level of awareness that diabetes mellitus can be caused by mitochondrial disease and to exercise caution in the prescription of metformin.

Left Frontotemporal Region Plays a Key Role in Letter Fluency Task-Evoked Activation and Functional Connectivity in Normal Subjects: A Functional Near-Infrared Spectroscopy Study.

Letter fluency task (LFT) is a tool that measures memory, executive function, and language function but lacks a definite cutoff value to define abnormalities. We used the optical signals of functional near-infrared spectroscopy (fNIRS) to study the differences in power and connectivity between the high-functioning and low-functioning participants while performing three successive LFTs, as well as the relationships between the brain network/power and LFT performance. We found that the most differentiating factor between these two groups was network topology rather than activation power. The high-functional group (7 men and 10 women) displayed higher left intra-hemispheric global efficiency, nodal strength, and shorter characteristic path length in the first section. They then demonstrated a higher power over the left Broca's area than the right corresponding area in the latter two sections. The low-LFT group (9 men and 11 women) displayed less left-lateralized connectivity and activation power. LFT performance was only related to the network topology rather than the power values, which was only presented in the low-functioning group in the second section. The direct correlation between power and connectivity primarily existed in the inter-hemispheric network, with the timing relationship also seeming to be present. In conclusion, the high-functioning group presented more prominent left-lateralized intra-hemispheric network connectivity and power activation, particularly in the Broca's area. The low-functioning group seemed to prefer using other networks, like the inter-hemispheric, rather than having a single focus on left intra-hemispheric connectivity. The network topology seemed to better reflect the LFT performance than did the power values.

Genomic Variation-Mediating Fluconazole Resistance in Yeast.

Fungal infections pose a serious and growing threat to public health. These infections can be treated with antifungal drugs by killing hazardous fungi in the body. However, the resistance can develop over time when fungi are exposed to antifungal drugs by generating genomic variations, including mutation, aneuploidy, and loss of heterozygosity. The variations could reduce the binding affinity of a drug to its target or block the pathway through which drugs exert their activity. Here, we review genomic variation-mediating fluconazole resistance in the yeast Candida, with the hope of highlighting the functional consequences of genomic variations for the antifungal resistance.

UGT1A1*6 mutation associated with the occurrence and severity in infants with prolonged jaundice.

Background: This study aimed to investigate the influence of a variant of the UGT1A1 gene on the occurrence and severity of prolonged jaundice in Chinese infants at term. Methods: 175 infants with prolonged jaundice and 149 controls were used in this retrospective case-control study. The infants with prolonged jaundice were subdivided into the mild-medium and severe jaundice groups (TSB ≥ 342 µmol/L). The frequency and genotype distribution of the UGT1A1 and G6PD genes, and clinical parameters including sex, birth weight, delivery mode, gestational age, and feeding mode, were analyzed, and the differences in the parameters between the two groups were compared. Results: The allele frequency of UGT1A1*6 in the prolonged jaundice group was higher than that in the control group. Similarly, it was also higher in the severe jaundice group than in the mild-medium jaundice group. Homozygous and heterozygous UGT1A1*6 were also found more frequently in the prolonged jaundice group than in the control group. Exclusive breastfeeding, homozygous and heterozygous forms of UGT1A1*6 were significant risk indicators for prolonged jaundice. Moreover, UGT1A1*6 was the best predictor of prolonged severe jaundice. Conclusion: UGT1A1*6 appears to be a risk factor for prolonged jaundice with hyperbilirubinemia in term infants of Chinese ancestry who are exclusively breastfed.